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Cancer Chemotherapy and Pharmacology

Erschienen in:

07.08.2019 | Review Article

Prodrugs as drug delivery system in oncology

verfasst von: J. Delahousse, C. Skarbek, A. Paci

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2019

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Abstract

The use of conventional chemotherapy in the treatment of cancer has been restricted by the lack of cell specificity, which causes toxicity regarding healthy cells resulting in limiting side effects responsible for low therapeutic efficiency. To overcome these drawbacks, the design of prodrugs has evolved and improved by covalently linking the drug through a degradable spacer. The use of these prodrugs as drug delivery systems, which are able to inactivate the drug during its biodistribution to specifically deliver the drug to its target, is an important breakthrough in cancer therapy. This strategy consisting in the covalent binding of a promoiety to daily used therapeutic compounds has been clinically proven in the design of targeted prodrugs leading enhanced therapeutic efficacy and increase of the therapeutic index. This review summarizes and compares several strategies that improve the therapeutic index of chemotherapy (i.e. conventional drugs) by their chemical transformation into prodrugs improving pharmacokinetic profiles and optimizing administration routes in comparison to the initial drug. This review provides an overview of the methods used to control the structure and function of prodrugs and, ultimately, their current and future potential in increasing the therapeutic index of daily used anticancer drugs. First, prodrugs’ design and their activation within the tumor microenvironment or within the tumor cell will be exposed. Then, the different strategies used leading to these prodrugs will be presented.

Lesniewska-Kowiel MA, Muszalska I (2017) Strategies in the designing of prodrugs, taking into account the antiviral and anticancer compounds. Eur J Med Chem 129:53–71. https://doi.org/10.1016/j.ejmech.2017.02.011 CrossRefPubMed

Singh Y, Palombo M, Sinko PJ (2008) Recent trends in targeted anticancer prodrug and conjugate design. Curr Med Chem 15(18):1802–1826CrossRefPubMedPubMedCentral

Soyez H, Schacht E, Vanderkerken S (1996) The crucial role of spacer groups in macromolecular prodrug design. Adv Drug Deliv Rev 21(2):81–106. https://doi.org/10.1016/s0169-409x(96)00400-0 CrossRef

Muller CE (2009) Prodrug approaches for enhancing the bioavailability of drugs with low solubility. Chem Biodivers 6(11):2071–2083. https://doi.org/10.1002/cbdv.200900114 CrossRefPubMed

Heynick F (2009) The original ‘magic bullet’ is 100 years old—extra. Br J Psychiatry 195(5):456. https://doi.org/10.1192/bjp.195.5.456 CrossRefPubMed

Albert A (1958) Chemical aspects of selective toxicity. Nature 182(4633):421–422. https://doi.org/10.1038/182421a0 CrossRefPubMed

Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Jarvinen T, Savolainen J (2008) Prodrugs: design and clinical applications. Nat Rev Drug Discov 7(3):255–270. https://doi.org/10.1038/nrd2468 CrossRefPubMed

Mahato R, Tai W, Cheng K (2011) Prodrugs for improving tumor targetability and efficiency. Adv Drug Deliv Rev 63(8):659–670. https://doi.org/10.1016/j.addr.2011.02.002 CrossRefPubMedPubMedCentral

Gupta D, Gupta SV, Lee KD, Amidon GL (2009) Chemical and enzymatic stability of amino acid prodrugs containing methoxy, ethoxy and propylene glycol linkers. Mol Pharm 6(5):1604–1611. https://doi.org/10.1021/mp900084v CrossRefPubMedPubMedCentral

10.

Walther R, Rautio J, Zelikin AN (2017) Prodrugs in medicinal chemistry and enzyme prodrug therapies. Adv Drug Deliv Rev 118:65–77. https://doi.org/10.1016/j.addr.2017.06.013 CrossRefPubMed

11.

Alouane A, Labruere R, Le Saux T, Schmidt F, Jullien L (2015) Self-immolative spacers: kinetic aspects, structure–property relationships, and applications. Angew Chem Int Ed Engl 54(26):7492–7509. https://doi.org/10.1002/anie.201500088 CrossRefPubMed

12.

Ye M, Han Y, Tang J, Piao Y, Liu X, Zhou Z, Gao J, Rao J, Shen Y (2017) A tumor-specific cascade amplification drug release nanoparticle for overcoming multidrug resistance in cancers. Adv Mater 29(38):1702342. https://doi.org/10.1002/adma.201702342 CrossRef

13.

Bildstein L, Pili B, Marsaud V, Wack S, Meneau F, Lepetre-Mouelhi S, Desmaele D, Bourgaux C, Couvreur P, Dubernet C (2011) Interaction of an amphiphilic squalenoyl prodrug of gemcitabine with cellular membranes. Eur J Pharm Biopharm 79(3):612–620. https://doi.org/10.1016/j.ejpb.2011.07.003 CrossRefPubMed

14.

Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33(9):941–951. https://doi.org/10.1038/nbt.3330 CrossRefPubMedPubMedCentral

15.

Maeda H, Nakamura H, Fang J (2013) The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65(1):71–79. https://doi.org/10.1016/j.addr.2012.10.002 CrossRefPubMed

16.

Greish K (2010) enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting. In: Grobmyer SR, Moudgil BM (eds) Cancer nanotechnology: methods and protocols. Humana Press, Totowa, pp 25–37. https://doi.org/10.1007/978-1-60761-609-2_3 CrossRef

17.

Nichols JW, Bae YH (2014) EPR: evidence and fallacy. J Control Release 190:451–464. https://doi.org/10.1016/j.jconrel.2014.03.057 CrossRefPubMed

18.

Bansal R, Post E, Proost JH, de Jager-Krikken A, Poelstra K, Prakash J (2011) PEGylation improves pharmacokinetic profile, liver uptake and efficacy of interferon gamma in liver fibrosis. J Control Release 154(3):233–240. https://doi.org/10.1016/j.jconrel.2011.05.027 CrossRefPubMed

19.

Choi KY, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Choi K, Jeong SY (2011) PEGylation of hyaluronic acid nanoparticles improves tumor targetability in vivo. Biomaterials 32(7):1880–1889. https://doi.org/10.1016/j.biomaterials.2010.11.010 CrossRefPubMed

20.

Piktel E, Niemirowicz K, Watek M, Wollny T, Deptula P, Bucki R (2016) Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy. J Nanobiotechnol 14(1):39. https://doi.org/10.1186/s12951-016-0193-x CrossRef

21.

Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41(7):2971–3010. https://doi.org/10.1039/c2cs15344k CrossRefPubMedPubMedCentral

22.

Khandare JJ, Jayant S, Singh A, Chandna P, Wang Y, Vorsa N, Minko T (2006) Dendrimer versus linear conjugate: influence of polymeric architecture on the delivery and anticancer effect of paclitaxel. Bioconjug Chem 17(6):1464–1472. https://doi.org/10.1021/bc060240p CrossRefPubMed

23.

Langer CJ, O’Byrne KJ, Socinski MA, Mikhailov SM, Lesniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ (2008) Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naive advanced non-small cell lung cancer. J Thorac Oncol 3(6):623–630. https://doi.org/10.1097/JTO.0b013e3181753b4b CrossRefPubMed

24.

Cheng C, Jiang-Ling Z, Xue H, Fei S, Xiu-Li W, Yu-Zhong W (2014) A prodrug strategy based on chitosan for efficient intracellular anticancer drug delivery. Nanotechnology 25(25):255101CrossRef

25.

Dragojevic S, Ryu JS, Raucher D (2015) Polymer-based prodrugs: improving tumor targeting and the solubility of small molecule drugs in cancer therapy. Molecules 20(12):21750–21769. https://doi.org/10.3390/molecules201219804 CrossRefPubMedPubMedCentral

26.

Fumagalli G, Marucci C, Christodoulou MS, Stella B, Dosio F, Passarella D (2016) Self-assembly drug conjugates for anticancer treatment. Drug Discov Today 21(8):1321–1329. https://doi.org/10.1016/j.drudis.2016.06.018 CrossRefPubMed

27.

Zhou M, Zhang RH, Wang M, Xu GB, Liao SG (2017) Prodrugs of triterpenoids and their derivatives. Eur J Med Chem 131:222–236. https://doi.org/10.1016/j.ejmech.2017.03.005 CrossRefPubMed

28.

Maksimenko A, Dosio F, Mougin J, Ferrero A, Wack S, Reddy LH, Weyn AA, Lepeltier E, Bourgaux C, Stella B, Cattel L, Couvreur P (2014) A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity. Proc Natl Acad Sci USA 111(2):E217–E226. https://doi.org/10.1073/pnas.1313459110 CrossRefPubMedPubMedCentral

29.

Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12(11):991–1003. https://doi.org/10.1038/nmat3776 CrossRefPubMed

30.

Siafaka PI, Ustundag Okur N, Karavas E, Bikiaris DN (2016) Surface modified multifunctional and stimuli responsive nanoparticles for drug targeting: current status and uses. Int J Mol Sci. https://doi.org/10.3390/ijms17091440 CrossRefPubMedPubMedCentral

31.

Chau Y, Padera RF, Dang NM, Langer R (2006) Antitumor efficacy of a novel polymer-peptide-drug conjugate in human tumor xenograft models. Int J Cancer 118(6):1519–1526. https://doi.org/10.1002/ijc.21495 CrossRefPubMed

32.

Huang C, Yi X, Kong D, Chen L, Min G (2016) Controlled release strategy of paclitaxel by conjugating to matrix metalloproteinases-2 sensitive peptide. Oncotarget 7(32):52230–52238. https://doi.org/10.18632/oncotarget.10735 CrossRefPubMedPubMedCentral

33.

Denmeade SR, Nagy A, Gao J, Lilja H, Schally AV, Isaacs JT (1998) Enzymatic activation of a doxorubicin-peptide prodrug by prostate-specific antigen. Cancer Res 58(12):2537–2540PubMed

34.

DiPaola RS, Rinehart J, Nemunaitis J, Ebbinghaus S, Rubin E, Capanna T, Ciardella M, Doyle-Lindrud S, Goodwin S, Fontaine M, Adams N, Williams A, Schwartz M, Winchell G, Wickersham K, Deutsch P, Yao SL (2002) Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer. J Clin Oncol 20(7):1874–1879. https://doi.org/10.1200/JCO.2002.07.001 CrossRefPubMed

35.

Wu X, Hu L (2016) Design and synthesis of peptide conjugates of phosphoramide mustard as prodrugs activated by prostate-specific antigen. Bioorg Med Chem 24(12):2697–2706. https://doi.org/10.1016/j.bmc.2016.04.035 CrossRefPubMed

36.

DeFeo-Jones D, Brady SF, Feng DM, Wong BK, Bolyar T, Haskell K, Kiefer DM, Leander K, McAvoy E, Lumma P, Pawluczyk JM, Wai J, Motzel SL, Keenan K, Van Zwieten M, Lin JH, Garsky VM, Freidinger R, Oliff A, Jones RE (2002) A prostate-specific antigen (PSA)-activated vinblastine prodrug selectively kills PSA-secreting cells in vivo. Mol Cancer Ther 1(7):451–459PubMed

37.

Brennen WN, Rosen DM, Wang H, Isaacs JT, Denmeade SR (2012) Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug. J Natl Cancer Inst 104(17):1320–1334. https://doi.org/10.1093/jnci/djs336 CrossRefPubMedPubMedCentral

38.

Chen M, Lei X, Shi C, Huang M, Li X, Wu B, Li Z, Han W, Du B, Hu J, Nie Q, Mai W, Ma N, Xu N, Zhang X, Fan C, Hong A, Xia M, Luo L, Ma A, Li H, Yu Q, Chen H, Zhang D, Ye W (2017) Pericyte-targeting prodrug overcomes tumor resistance to vascular disrupting agents. J Clin Investig 127(10):3689–3701. https://doi.org/10.1172/JCI94258 CrossRefPubMedPubMedCentral

39.

Huang S, Zhang Y, Zhong J, Pan Y, Cai S, Xu J (2018) Toxicological profile and safety pharmacology of a single dose of fibroblast activation protein-alpha-based doxorubicin prodrug: in vitro and in vivo evaluation. Anticancer Drugs 29(3):253–261. https://doi.org/10.1097/CAD.0000000000000593 CrossRefPubMed

40.

Wang J, Li Q, Li X, Yuan W, Huang S, Cai S, Xu J (2017) A novel FAPalpha-based Z-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy. Eur J Pharmacol 815:166–172. https://doi.org/10.1016/j.ejphar.2017.09.016 CrossRefPubMed

41.

Aggarwal N, Sloane BF (2014) Cathepsin B: multiple roles in cancer. Proteom Clin Appl 8(5–6):427–437. https://doi.org/10.1002/prca.201300105 CrossRef

42.

Shao LH, Liu SP, Hou JX, Zhang YH, Peng CW, Zhong YJ, Liu X, Liu XL, Hong YP, Firestone RA, Li Y (2012) Cathepsin B cleavable novel prodrug Ac-Phe-Lys-PABC-ADM enhances efficacy at reduced toxicity in treating gastric cancer peritoneal carcinomatosis: an experimental study. Cancer 118(11):2986–2996. https://doi.org/10.1002/cncr.26596 CrossRefPubMed

43.

Zhong YJ, Shao LH, Li Y (2013) Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy (review). Int J Oncol 42(2):373–383. https://doi.org/10.3892/ijo.2012.1754 CrossRefPubMed

44.

Seymour LW, Ferry DR, Kerr DJ, Rea D, Whitlock M, Poyner R, Boivin C, Hesslewood S, Twelves C, Blackie R, Schatzlein A, Jodrell D, Bissett D, Calvert H, Lind M, Robbins A, Burtles S, Duncan R, Cassidy J (2009) Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol 34(6):1629–1636. https://doi.org/10.3892/ijo_00000293 CrossRefPubMed

45.

Paz-Ares L, Ross H, O’Brien M, Riviere A, Gatzemeier U, Von Pawel J, Kaukel E, Freitag L, Digel W, Bischoff H, Garcia-Campelo R, Iannotti N, Reiterer P, Bover I, Prendiville J, Eisenfeld AJ, Oldham FB, Bandstra B, Singer JW, Bonomi P (2008) Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer. Br J Cancer 98(10):1608–1613. https://doi.org/10.1038/sj.bjc.6604372 CrossRefPubMedPubMedCentral

46.

Zhang M, Jiang Z, Chen S, Wu Z, Chen K, Wu Y (2018) Legumain correlates with neuroblastoma differentiation and can be used in prodrug design. Chem Biol Drug Des 91(2):534–544. https://doi.org/10.1111/cbdd.13116 CrossRefPubMed

47.

Connors JMRJ (2018) Brentuximab vedotin for stage III or IV Hodgkin’s lymphoma. N Engl J Med 378(16):1558–1561. https://doi.org/10.1056/NEJMc1802363 CrossRef

48.

Karnthaler-Benbakka C, Koblmuller B, Mathuber M, Holste K, Berger W, Heffeter P, Kowol CR, Keppler BK (2018) Synthesis, characterization and in vitro studies of a Cathepsin B-cleavable prodrug of the VEGFR inhibitor sunitinib. Chem Biodivers. https://doi.org/10.1002/cbdv.201800520 CrossRefPubMedPubMedCentral

49.

Bollag W (1965) Hartmann HR (1980) tumor inhibitory effects of a new fluorouracil derivative: 5′-deoxy-5-fluorouridine. Eur J Cancer 16(4):427–432. https://doi.org/10.1016/0014-2964(80)90221-2 CrossRef

50.

Hiller SA, Lidak MY, Zhuk RA et al (1969) Analogs of pyrimidine nucleosides. Chem Heterocycl Compd 5(2):283–285. https://doi.org/10.1007/BF00943946 CrossRef

51.

Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J (2008) Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules 13(8):1897–1922. https://doi.org/10.3390/molecules13081897 CrossRefPubMedPubMedCentral

52.

Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T (1998) Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 34(11):1715–1720. https://doi.org/10.1016/s0959-8049(98)00211-1 CrossRefPubMed

53.

Alberto P, Winkelmann JJ, Paschoud N, Peytremann R, Bruyere A, Righetti A, Decoster G, Holdener EE (1989) Phase I study of oral doxifluridine using two schedules. Eur J Cancer Clin Oncol 25(5):905–908. https://doi.org/10.1016/0277-5379(89)90139-9 CrossRefPubMed

54.

Kim NK, Min JS, Park JK, Yun SH, Sung JS, Jung HC, Roh JK (2001) Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer: prospective randomized trials. Jpn J Clin Oncol 31(1):25–29. https://doi.org/10.1093/jjco/hye009 CrossRefPubMed

55.

van Oosterom AT, ten Bokkel Huinink WW, van der Burg ME, Vermorken JB, Willemse PH, Neijt JP (1991) Phase II clinical trial of doxifluridine in patients with advanced ovarian cancer. Eur J Cancer 27(6):747–749. https://doi.org/10.1016/0277-5379(91)90180-L CrossRefPubMed

56.

Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H (1998) Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34(8):1274–1281. https://doi.org/10.1016/s0959-8049(98)00058-6 CrossRefPubMed

57.

Ter Veer E, Ngai LL, Valkenhoef GV, Mohammad NH, Anderegg MCJ, van Oijen MGH, van Laarhoven HWM (2017) Capecitabine, 5-fluorouracil and S-1 based regimens for previously untreated advanced oesophagogastric cancer: a network meta-analysis. Sci Rep 7(1):7142. https://doi.org/10.1038/s41598-017-07750-3 CrossRefPubMedPubMedCentral

58.

Fukushima M, Iizuka K, Jin C, Zhang C, Hong M, Eshima K (2017) Development of new promising antimetabolite, DFP-11207 with self-controlled toxicity in rodents. Drug Des Dev Ther 11:1693–1705. https://doi.org/10.2147/DDDT.S128420 CrossRef

59.

Zhao D, Zhang H, Tao W, Wei W, Sun J, He Z (2017) A rapid albumin-binding 5-fluorouracil prodrug with a prolonged circulation time and enhanced antitumor activity. Biomater Sci 5(3):502–510. https://doi.org/10.1039/c6bm00884d CrossRefPubMed

60.

Dubois V, Dasnois L, Lebtahi K, Collot F, Heylen N, Havaux N, Fernandez AM, Lobl TJ, Oliyai C, Nieder M, Shochat D, Yarranton GT, Trouet A (2002) CPI-0004Na, a new extracellularly tumor-activated prodrug of doxorubicin: in vivo toxicity, activity, and tissue distribution confirm tumor cell selectivity. Cancer Res 62(8):2327–2331PubMed

61.

Schoffski P, Delord JP, Brain E, Robert J, Dumez H, Gasmi J, Trouet A (2017) First-in-man phase I study assessing the safety and pharmacokinetics of a 1-h intravenous infusion of the doxorubicin prodrug DTS-201 every 3 weeks in patients with advanced or metastatic solid tumours. Eur J Cancer 86:240–247. https://doi.org/10.1016/j.ejca.2017.09.009 CrossRefPubMed

62.

Cornillie J, Wozniak A, Pokreisz P, Casazza A, Vreys L, Wellens J, Vanleeuw U, Gebreyohannes YK, Debiec-Rychter M, Sciot R, Hompes D, Schoffski P (2017) In vivo antitumoral efficacy of PhAc-ALGP-doxorubicin, an enzyme-activated doxorubicin prodrug, in patient-derived soft tissue sarcoma xenograft models. Mol Cancer Ther 16(8):1566–1575. https://doi.org/10.1158/1535-7163.MCT-16-0832 CrossRefPubMed

63.

Vandooren J, Opdenakker G, Loadman PM, Edwards DR (2016) Proteases in cancer drug delivery. Adv Drug Deliv Rev 97:144–155. https://doi.org/10.1016/j.addr.2015.12.020 CrossRefPubMed

64.

Wu W, Luo Y, Sun C, Liu Y, Kuo P, Varga J, Xiang R, Reisfeld R, Janda KD, Edgington TS, Liu C (2006) Targeting cell-impermeable prodrug activation to tumor microenvironment eradicates multiple drug-resistant neoplasms. Cancer Res 66(2):970–980. https://doi.org/10.1158/0008-5472.CAN-05-2591 CrossRefPubMed

65.

Zhou H, Sun H, Lv S, Zhang D, Zhang X, Tang Z, Chen X (2017) Legumain-cleavable 4-arm poly(ethylene glycol)-doxorubicin conjugate for tumor specific delivery and release. Acta Biomater 54:227–238. https://doi.org/10.1016/j.actbio.2017.03.019 CrossRefPubMed

66.

Stern L, Perry R, Ofek P, Many A, Shabat D, Satchi-Fainaro R (2009) A novel antitumor prodrug platform designed to be cleaved by the endoprotease legumain. Bioconjug Chem 20(3):500–510. https://doi.org/10.1021/bc800448u CrossRefPubMed

67.

Zhang H, Sun Z, Wang K, Li N, Chen H, Tan X, Li L, He Z, Sun J (2018) Multifunctional tumor-targeting cathepsin B-sensitive gemcitabine prodrug covalently targets albumin in situ and improves cancer therapy. Bioconjug Chem 29(6):1852–1858. https://doi.org/10.1021/acs.bioconjchem.8b00223 CrossRefPubMed

68.

Wu W, Luo Y, Sun C, Liu Y, Kuo P, Varga J, Xiang R, Reisfeld R, Janda KD, Edgington TS, Liu C (2006) Targeting cell-impermeable prodrug activation to tumor microenvironment eradicates multiple drug-resistant neoplasms. Can Res 66(2):970. https://doi.org/10.1158/0008-5472.CAN-05-2591 CrossRef

69.

Seo K, Chung SW, Byun Y, Kim D (2012) Paclitaxel loaded nano-aggregates based on pH sensitive polyaspartamide amphiphilic graft copolymers. Int J Pharm 424(1–2):26–32. https://doi.org/10.1016/j.ijpharm.2011.12.047 CrossRefPubMed

70.

Yoshida T, Lai TC, Kwon GS, Sako K (2013) pH- and ion-sensitive polymers for drug delivery. Expert Opin Drug Deliv 10(11):1497–1513. https://doi.org/10.1517/17425247.2013.821978 CrossRefPubMedPubMedCentral

71.

Xiong S, Wang Z, Liu J, Deng X, Xiong R, Cao X, Xie Z, Lei X, Chen Y, Tang G (2019) A pH-sensitive prodrug strategy to co-deliver DOX and TOS in TPGS nanomicelles for tumor therapy. Colloids Surf B Biointerfaces 173:346–355. https://doi.org/10.1016/j.colsurfb.2018.10.012 CrossRefPubMed

72.

Huang X, Liao W, Xie Z, Chen D, Zhang CY (2018) A pH-responsive prodrug delivery system self-assembled from acid-labile doxorubicin-conjugated amphiphilic pH-sensitive block copolymers. Mater Sci Eng C Mater Biol Appl 90:27–37. https://doi.org/10.1016/j.msec.2018.04.036 CrossRefPubMed

73.

Rahoui N, Jiang B, Taloub N, Hegazy M, Huang YD (2018) Synthesis and evaluation of water soluble pH sensitive poly (vinyl alcohol)-doxorubicin conjugates. J Biomater Sci Polym Ed 29(12):1482–1497. https://doi.org/10.1080/09205063.2018.1466470 CrossRefPubMed

74.

Zhu J, Huo Q, Xu M, Yang F, Li Y, Shi H, Niu Y, Liu Y (2018) Bortezomib-catechol conjugated prodrug micelles: combining bone targeting and aryl boronate-based pH-responsive drug release for cancer bone-metastasis therapy. Nanoscale 10(38):18387–18397. https://doi.org/10.1039/c8nr03899f CrossRefPubMed

75.

Xie J, Fan Z, Li Y, Zhang Y, Yu F, Su G, Xie L, Hou Z (2018) Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy. Int J Nanomed 13:1381–1398. https://doi.org/10.2147/IJN.S152312 CrossRef

76.

Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P (2017) Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol 18(8):1089–1103. https://doi.org/10.1016/s1470-2045(17)30381-9 CrossRefPubMedPubMedCentral

77.

Laubach JP, Liu CJ, Raje NS, Yee AJ, Armand P, Schlossman RL, Rosenblatt J, Hedlund J, Martin M, Reynolds C, Shain KH, Zackon I, Stampleman L, Henrick P, Rivotto B, Hornburg KTV, Dumke HJ, Chuma S, Savell A, Handisides DR, Kroll S, Anderson KC, Richardson PG, Ghobrial IM (2018) A phase I/II study of evofosfamide, a hypoxia-activated prodrug with or without bortezomib in subjects with relapsed/refractory multiple myeloma. Clin Cancer Res. https://doi.org/10.1158/1078-0432.ccr-18-1325 CrossRefPubMedPubMedCentral

78.

Jamieson SM, Tsai P, Kondratyev MK, Budhani P, Liu A, Senzer NN, Chiorean EG, Jalal SI, Nemunaitis JJ, Kee D, Shome A, Wong WW, Li D, Poonawala-Lohani N, Kakadia PM, Knowlton NS, Lynch CR, Hong CR, Lee TW, Grenman RA, Caporiccio L, McKee TD, Zaidi M, Butt S, Macann AM, McIvor NP, Chaplin JM, Hicks KO, Bohlander SK, Wouters BG, Hart CP, Print CG, Wilson WR, Curran MA, Hunter FW (2018) Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma. JCI Insight. https://doi.org/10.1172/jci.insight.122204 CrossRefPubMedPubMedCentral

79.

Kumar S, Sun JD, Zhang L, Mokhtari RB, Wu B, Meng F, Liu Q, Bhupathi D, Wang Y, Yeger H, Hart C, Baruchel S (2018) Hypoxia-targeting drug evofosfamide (TH-302) enhances sunitinib activity in neuroblastoma xenograft models. Transl Oncol 11(4):911–919. https://doi.org/10.1016/j.tranon.2018.05.004 CrossRefPubMedPubMedCentral

80.

Liu S, Tetzlaff M, Wang T, Chen X, Yang R, Kumar SM, Xu X (2017) Hypoxia-activated prodrug enhances therapeutic effect of sunitinib in melanoma. Oncotarget 8(70):115140–115152. https://doi.org/10.18632/oncotarget.22944 CrossRefPubMedPubMedCentral

81.

Huang Y, Tian Y, Zhao Y, Xue C, Zhan J, Liu L, He X, Zhang L (2018) Efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in nasopharyngeal carcinoma in vitro and in vivo. Cancer Commun (Lond) 38(1):15. https://doi.org/10.1186/s40880-018-0285-0 CrossRef

82.

Brenner A, Zuniga R, Sun JD, Floyd J, Hart CP, Kroll S, Fichtel L, Cavazos D, Caflisch L, Gruslova A, Huang S, Liu Y, Lodi A, Tiziani S (2018) Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study. Neurooncology 20(9):1231–1239. https://doi.org/10.1093/neuonc/noy015 CrossRef

83.

Liapis V, Zysk A, DeNichilo M, Zinonos I, Hay S, Panagopoulos V, Shoubridge A, Difelice C, Ponomarev V, Ingman W, Atkins GJ, Findlay DM, Zannettino ACW, Evdokiou A (2017) Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma. Cancer Med 6(9):2164–2176. https://doi.org/10.1002/cam4.1115 CrossRefPubMedPubMedCentral

84.

Hajj C, Russell J, Hart CP, Goodman KA, Lowery MA, Haimovitz-Friedman A, Deasy JO, Humm JL (2017) A combination of radiation and the hypoxia-activated prodrug evofosfamide (TH-302) is efficacious against a human orthotopic pancreatic tumor model. Transl Oncol 10(5):760–765. https://doi.org/10.1016/j.tranon.2017.06.010 CrossRefPubMedPubMedCentral

85.

Jin C, Zhang Q, Lu W (2017) Synthesis and biological evaluation of hypoxia-activated prodrugs of SN-38. Eur J Med Chem 132:135–141. https://doi.org/10.1016/j.ejmech.2017.03.040 CrossRefPubMed

86.

McKeage MJ, Gu Y, Wilson WR, Hill A, Amies K, Melink TJ, Jameson MB (2011) A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients. BMC Cancer 11:432. https://doi.org/10.1186/1471-2407-11-432 CrossRefPubMedPubMedCentral

87.

Guise CP, Abbattista MR, Singleton RS, Holford SD, Connolly J, Dachs GU, Fox SB, Pollock R, Harvey J, Guilford P, Donate F, Wilson WR, Patterson AV (2010) The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res 70(4):1573–1584. https://doi.org/10.1158/0008-5472.CAN-09-3237 CrossRefPubMed

88.

Konopleva M, Thall PF, Yi CA, Borthakur G, Coveler A, Bueso-Ramos C, Benito J, Konoplev S, Gu Y, Ravandi F, Jabbour E, Faderl S, Thomas D, Cortes J, Kadia T, Kornblau S, Daver N, Pemmaraju N, Nguyen HQ, Feliu J, Lu H, Wei C, Wilson WR, Melink TJ, Gutheil JC, Andreeff M, Estey EH, Kantarjian H (2015) Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia. Haematologica 100(7):927–934. https://doi.org/10.3324/haematol.2014.118455 CrossRefPubMedPubMedCentral

89.

Peng X, Gandhi V (2012) ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage. Ther Deliv 3(7):823–833. https://doi.org/10.4155/tde.12.61 CrossRefPubMed

90.

Saravanakumar G, Kim J, Kim Won J (2016) Reactive-oxygen-species-responsive drug delivery systems: promises and challenges. Adv Sci 4(1):1600124. https://doi.org/10.1002/advs.201600124 CrossRef

91.

Kuang Y, Balakrishnan K, Gandhi V, Peng X (2011) Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs. J Am Chem Soc 133(48):19278–19281. https://doi.org/10.1021/ja2073824 CrossRefPubMedPubMedCentral

92.

Wang L, Xie S, Ma L, Chen Y, Lu W (2016) 10-Boronic acid substituted camptothecin as prodrug of SN-38. Eur J Med Chem 116:84–89. https://doi.org/10.1016/j.ejmech.2016.03.063 CrossRefPubMed

93.

Zhang C, Zhong Q, Zhang Q, Zheng S, Miele L, Wang G (2015) Boronic prodrug of endoxifen as an effective hormone therapy for breast cancer. Breast Cancer Res Treat 152(2):283–291. https://doi.org/10.1007/s10549-015-3461-9 CrossRefPubMedPubMedCentral

94.

Gabor F, Wollmann K, Theyer G, Haberl I, Hamilton G (1994) In vitro antiproliferative effects of albumin-doxorubicin conjugates against Ewing’s sarcoma and peripheral neuroectodermal tumor cells. Anticancer Res 14(5A):1943–1950PubMed

95.

Kratz F (2007) DOXO-EMCH (INNO-206): the first albumin-binding prodrug of doxorubicin to enter clinical trials. Expert Opin Investig Drugs 16(6):855–866. https://doi.org/10.1517/13543784.16.6.855 CrossRefPubMed

96.

Chawla SP, Papai Z, Mukhametshina G, Sankhala K, Vasylyev L, Fedenko A, Khamly K, Ganjoo K, Nagarkar R, Wieland S, Levitt DJ (2015) First-line aldoxorubicin vs doxorubicin in metastatic or locally advanced unresectable soft-tissue sarcoma: a phase 2b randomized clinical trial. JAMA Oncol 1(9):1272–1280. https://doi.org/10.1001/jamaoncol.2015.3101 CrossRefPubMed

97.

Mita MM, Natale RB, Wolin EM, Laabs B, Dinh H, Wieland S, Levitt DJ, Mita AC (2015) Pharmacokinetic study of aldoxorubicin in patients with solid tumors. Investig New Drugs 33(2):341–348. https://doi.org/10.1007/s10637-014-0183-5 CrossRef

98.

Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Fichtner I, Kratz F (2003) A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Can Res 63(14):4062

99.

Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F (2007) Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem 18(3):702–716. https://doi.org/10.1021/bc0602735 CrossRefPubMed

100.

Graeser R, Chung DE, Esser N, Moor S, Schachtele C, Unger C, Kratz F (2008) Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP). Int J Cancer 122(5):1145–1154. https://doi.org/10.1002/ijc.23050 CrossRefPubMed

101.

Wunder A, Stehle G, Schrenk HH, Hartung G, Heene DL, Maier-Borst W, Sinn H (1998) Antitumor activity of methotrexate-albumin conjugates in rats bearing a Walker-256 carcinoma. Int J Cancer 76(6):884–890. https://doi.org/10.1002/(SICI)1097-0215(19980610)76:6%3c884:AID-IJC19%3e3.0.CO;2-2 CrossRefPubMed

102.

Hartung G, Stehle G, Sinn H, Wunder A, Schrenk HH, Heeger S, Kranzle M, Edler L, Frei E, Fiebig HH, Heene DL, Maier-Borst W, Queisser W (1999) Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society. Clin Cancer Res 5(4):753–759PubMed

103.

Vis AN, van der Gaast A, van Rhijn BW, Catsburg TK, Schmidt C, Mickisch GH (2002) A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy. Cancer Chemother Pharmacol 49(4):342–345. https://doi.org/10.1007/s00280-001-0417-z CrossRefPubMed

104.

Mayr J, Heffeter P, Groza D, Galvez L, Koellensperger G, Roller A, Alte B, Haider M, Berger W, Kowol CR, Keppler BK (2017) An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo. Chem Sci 8(3):2241–2250. https://doi.org/10.1039/c6sc03862j CrossRefPubMed

105.

Beck A, D’Atri V, Ehkirch A, Fekete S, Hernandez-Alba O, Gahoual R, Leize-Wagner E, Francois Y, Guillarme D, Cianferani S (2019) Cutting-edge multi-level analytical and structural characterization of antibody–drug conjugates: present and future. Expert Rev Proteom 16(4):337–362. https://doi.org/10.1080/14789450.2019.1578215 CrossRef

106.

Jen EY, Ko CW, Lee JE, Del Valle PL, Aydanian A, Jewell C, Norsworthy KJ, Przepiorka D, Nie L, Liu J, Sheth CM, Shapiro M, Farrell AT, Pazdur R (2018) FDA approval: gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia. Clin Cancer Res 24(14):3242–3246. https://doi.org/10.1158/1078-0432.CCR-17-3179 CrossRefPubMed

107.

Tack DK, Letendre L, Kamath PS, Tefferi A (2001) Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia. Bone Marrow Transplant 28(9):895–897. https://doi.org/10.1038/sj.bmt.1703242 CrossRefPubMed

108.

Lu J, Jiang F, Lu A, Zhang G (2016) Linkers having a crucial role in antibody–drug conjugates. Int J Mol Sci 17(4):561. https://doi.org/10.3390/ijms17040561 CrossRefPubMedPubMedCentral

109.

Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX (2011) Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 128(2):347–356. https://doi.org/10.1007/s10549-010-1090-x CrossRefPubMed

110.

Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris Iii HA, LoRusso PM, Yi J-H, Saad O, Tong B, Chu Y-W, Holden S, Joshi A (2012) Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemother Pharmacol 69(5):1229–1240. https://doi.org/10.1007/s00280-011-1817-3 CrossRefPubMedPubMedCentral

111.

Joubert N, Denevault-Sabourin C, Bryden F, Viaud-Massuard MC (2017) Towards antibody–drug conjugates and prodrug strategies with extracellular stimuli-responsive drug delivery in the tumor microenvironment for cancer therapy. Eur J Med Chem 142:393–415. https://doi.org/10.1016/j.ejmech.2017.08.049 CrossRefPubMed

112.

Chen H, Lin Z, Arnst KE, Miller DD, Li W (2017) Tubulin inhibitor-based antibody–drug conjugates for cancer therapy. Molecules. https://doi.org/10.3390/molecules22081281 CrossRefPubMedPubMedCentral

113.

Riechelmann H, Sauter A, Golze W, Hanft G, Schroen C, Hoermann K, Erhardt T, Gronau S (2008) Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol 44(9):823–829. https://doi.org/10.1016/j.oraloncology.2007.10.009 CrossRefPubMed

114.

Dal Corso A, Cazzamalli S, Gebleux R, Mattarella M, Neri D (2017) Protease-cleavable linkers modulate the anticancer activity of noninternalizing antibody–drug conjugates. Bioconjug Chem 28(7):1826–1833. https://doi.org/10.1021/acs.bioconjchem.7b00304 CrossRef

115.

Perrino E, Steiner M, Krall N, Bernardes GJ, Pretto F, Casi G, Neri D (2014) Curative properties of noninternalizing antibody–drug conjugates based on maytansinoids. Cancer Res 74(9):2569–2578. https://doi.org/10.1158/0008-5472.CAN-13-2990 CrossRefPubMed

116.

Richards DA (2018) Exploring alternative antibody scaffolds: antibody fragments and antibody mimics for targeted drug delivery. Drug Discov Today Technol 30:35–46. https://doi.org/10.1016/j.ddtec.2018.10.005 CrossRefPubMed

117.

Aubrey N, Allard-Vannier E, Martin C, Bryden F, Letast S, Colas C, Lakhrif Z, Collinet N, Dimier-Poisson I, Chourpa I, Viaud-Massuard MC, Joubert N (2018) Site-specific conjugation of auristatins onto engineered scFv using second generation maleimide to target HER2-positive breast cancer in vitro. Bioconjug Chem 29(11):3516–3521. https://doi.org/10.1021/acs.bioconjchem.8b00668 CrossRefPubMed

118.

Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10(1):9–22. https://doi.org/10.1038/nrc2748 CrossRefPubMedPubMedCentral

119.

Dechantsreiter MA, Planker E, Matha B, Lohof E, Holzemann G, Jonczyk A, Goodman SL, Kessler H (1999) N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem 42(16):3033–3040. https://doi.org/10.1021/jm970832g CrossRefPubMed

120.

Massaguer A, Gonzalez-Canto A, Escribano E, Barrabes S, Artigas G, Moreno V, Marchan V (2015) Integrin-targeted delivery into cancer cells of a Pt(IV) pro-drug through conjugation to RGD-containing peptides. Dalton Trans 44(1):202–212. https://doi.org/10.1039/c4dt02710h CrossRefPubMed

121.

Dal Pozzo A, Esposito E, Ni M, Muzi L, Pisano C, Bucci F, Vesci L, Castorina M, Penco S (2010) Conjugates of a novel 7-substituted camptothecin with RGD-peptides as alpha(v)beta(3) integrin ligands: an approach to tumor-targeted therapy. Bioconjug Chem 21(11):1956–1967. https://doi.org/10.1021/bc100097r CrossRef

122.

Arosio D, Casagrande C (2016) Advancement in integrin facilitated drug delivery. Adv Drug Deliv Rev 97:111–143. https://doi.org/10.1016/j.addr.2015.12.001 CrossRefPubMed

123.

Zhong P, Gu X, Cheng R, Deng C, Meng F, Zhong Z (2017) alphavbeta3 integrin-targeted micellar mertansine prodrug effectively inhibits triple-negative breast cancer in vivo. Int J Nanomed 12:7913–7921. https://doi.org/10.2147/IJN.S146505 CrossRef

124.

Engel J, Emons G, Pinski J, Schally AV (2012) AEZS-108: a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors. Expert Opin Investig Drugs 21(6):891–899. https://doi.org/10.1517/13543784.2012.685128 CrossRefPubMed

125.

Emons G, Gorchev G, Sehouli J, Wimberger P, Stahle A, Hanker L, Hilpert F, Sindermann H, Grundker C, Harter P (2014) Efficacy and safety of AEZS-108 (INN: zoptarelin doxorubicin acetate) an LHRH agonist linked to doxorubicin in women with platinum refractory or resistant ovarian cancer expressing LHRH receptors: a multicenter phase II trial of the ago-study group (AGO GYN 5). Gynecol Oncol 133(3):427–432. https://doi.org/10.1016/j.ygyno.2014.03.576 CrossRefPubMed

126.

Liu SV, Tsao-Wei DD, Xiong S, Groshen S, Dorff TB, Quinn DI, Tai YC, Engel J, Hawes D, Schally AV, Pinski JK (2014) Phase I, dose-escalation study of the targeted cytotoxic LHRH analog AEZS-108 in patients with castration- and taxane-resistant prostate cancer. Clin Cancer Res 20(24):6277–6283. https://doi.org/10.1158/1078-0432.CCR-14-0489 CrossRefPubMed

127.

Yu SS, Athreya K, Liu SV, Schally AV, Tsao-Wei D, Groshen S, Quinn DI, Dorff TB, Xiong S, Engel J, Pinski J (2017) A phase II trial of AEZS-108 in castration- and taxane-resistant prostate cancer. Clin Genitourin Cancer 15(6):742–749. https://doi.org/10.1016/j.clgc.2017.06.002 CrossRefPubMed

128.

Karampelas T, Skavatsou E, Argyros O, Fokas D, Tamvakopoulos C (2017) Gemcitabine based peptide conjugate with improved metabolic properties and dual mode of efficacy. Mol Pharm 14(3):674–685. https://doi.org/10.1021/acs.molpharmaceut.6b00961 CrossRefPubMed

129.

Kurzrock R, Gabrail N, Chandhasin C, Moulder S, Smith C, Brenner A, Sankhala K, Mita A, Elian K, Bouchard D, Sarantopoulos J (2012) Safety, pharmacokinetics, and activity of GRN1005, a novel conjugate of angiopep-2, a peptide facilitating brain penetration, and paclitaxel, in patients with advanced solid tumors. Mol Cancer Ther 11(2):308–316. https://doi.org/10.1158/1535-7163.MCT-11-0566 CrossRefPubMed

130.

Drappatz J, Brenner A, Wong ET, Eichler A, Schiff D, Groves MD, Mikkelsen T, Rosenfeld S, Sarantopoulos J, Meyers CA, Fielding RM, Elian K, Wang X, Lawrence B, Shing M, Kelsey S, Castaigne JP, Wen PY (2013) Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res 19(6):1567–1576. https://doi.org/10.1158/1078-0432.CCR-12-2481 CrossRefPubMed

131.

Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37(13):1590–1598. https://doi.org/10.1016/S0959-8049(01)00171-X CrossRefPubMed

132.

Huo M, Zhu Q, Wu Q, Yin T, Wang L, Yin L, Zhou J (2015) Somatostatin receptor-mediated specific delivery of paclitaxel prodrugs for efficient cancer therapy. J Pharm Sci 104(6):2018–2028. https://doi.org/10.1002/jps.24438 CrossRefPubMed

133.

Steinberg G, Borch RF (2001) Synthesis and evaluation of pteroic acid-conjugated nitroheterocyclic phosphoramidates as folate receptor-targeted alkylating agents. J Med Chem 44(1):69–73. https://doi.org/10.1021/jm000306g CrossRefPubMed

134.

Aronov O, Horowitz AT, Gabizon A, Gibson D (2003) Folate-targeted PEG as a potential carrier for carboplatin analogs. Synthesis and in vitro studies. Bioconjug Chem 14(3):563–574. https://doi.org/10.1021/bc025642l CrossRefPubMed

135.

Liu J, Kolar C, Lawson TA, Gmeiner WH (2002) Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-Resistant human colorectal tumor cells. J Org Chem 67(8):2734. https://doi.org/10.1021/jo0161983 CrossRef

136.

Lee JW, Lu JY, Low PS, Fuchs PL (2002) Synthesis and evaluation of taxol–folic acid conjugates as targeted antineoplastics. Bioorg Med Chem 10(7):2397–2414. https://doi.org/10.1016/s0968-0896(02)00019-6 CrossRefPubMed

137.

Ladino CA, Chari RV, Bourret LA, Kedersha NL, Goldmacher VS (1997) Folate-maytansinoids: target-selective drugs of low molecular weight. Int J Cancer 73(6):859–864. https://doi.org/10.1002/(SICI)1097-0215(19971210)73:6%3c859:AID-IJC16%3e3.0.CO;2-%23 CrossRefPubMed

138.

Reddy JA, Westrick E, Santhapuram HK, Howard SJ, Miller ML, Vetzel M, Vlahov I, Chari RV, Goldmacher VS, Leamon CP (2007) Folate receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate. Cancer Res 67(13):6376–6382. https://doi.org/10.1158/0008-5472.CAN-06-3894 CrossRefPubMed

139.

Li J, Sausville EA, Klein PJ, Morgenstern D, Leamon CP, Messmann RA, LoRusso P (2009) Clinical pharmacokinetics and exposure-toxicity relationship of a folate-Vinca alkaloid conjugate EC145 in cancer patients. J Clin Pharmacol 49(12):1467–1476. https://doi.org/10.1177/0091270009339740 CrossRefPubMed

140.

Guertin AD, O’Neil J, Stoeck A, Reddy JA, Cristescu R, Haines BB, Hinton MC, Dorton R, Bloomfield A, Nelson M, Vetzel M, Lejnine S, Nebozhyn M, Zhang T, Loboda A, Picard KL, Schmidt EV, Dussault I, Leamon CP (2016) High levels of expression of p-glycoprotein/multidrug resistance protein result in resistance to vintafolide. Mol Cancer Ther 15(8):1998–2008. https://doi.org/10.1158/1535-7163.MCT-15-0950 CrossRefPubMed

141.

Shan L, Zhuo X, Zhang F, Dai Y, Zhu G, Yung BC, Fan W, Zhai K, Jacobson O, Kiesewetter DO, Ma Y, Gao G, Chen X (2018) A paclitaxel prodrug with bifunctional folate and albumin binding moieties for both passive and active targeted cancer therapy. Theranostics 8(7):2018–2030. https://doi.org/10.7150/thno.24382 CrossRefPubMedPubMedCentral

142.

Liu Z, Xiong M, Gong J, Zhang Y, Bai N, Luo Y, Li L, Wei Y, Liu Y, Tan X, Xiang R (2014) Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment. Nat Commun 5:4280. https://doi.org/10.1038/ncomms5280. https://www.nature.com/articles/ncomms5280#supplementary-information

143.

Zhang Y, Huang F, Ren C, Yang L, Liu J, Cheng Z, Chu L, Liu J (2017) Targeted chemo-photodynamic combination platform based on the DOX prodrug nanoparticles for enhanced cancer therapy. ACS Appl Mater Interfaces 9(15):13016–13028. https://doi.org/10.1021/acsami.7b00927 CrossRefPubMed

144.

Regina A, Demeule M, Che C, Lavallee I, Poirier J, Gabathuler R, Beliveau R, Castaigne JP (2008) Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep-2. Br J Pharmacol 155(2):185–197. https://doi.org/10.1038/bjp.2008.260 CrossRefPubMedPubMedCentral

145.

Reddy JA, Dorton R, Bloomfield A, Nelson M, Dircksen C, Vetzel M, Kleindl P, Santhapuram H, Vlahov IR, Leamon CP (2018) Pre-clinical evaluation of EC1456, a folate-tubulysin anti-cancer therapeutic. Sci Rep 8(1):8943. https://doi.org/10.1038/s41598-018-27320-5 CrossRefPubMedPubMedCentral

Titel: Prodrugs as drug delivery system in oncology
verfasst von: J. Delahousse
C. Skarbek
A. Paci
Publikationsdatum: 07.08.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03906-2

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Prodrugs as drug delivery system in oncology

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Blasenkarzinom – Biomarker statt Zytologie?

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

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