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Erschienen in: Cancer Chemotherapy and Pharmacology 2/2016

01.02.2016 | Original Article

Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes

verfasst von: Qian Lin, Kai-Li Mao, Fu-Rong Tian, Jing-Jing Yang, Pian-Pian Chen, Jie Xu, Zi-Liang Fan, Ya-Ping Zhao, Wen-Feng Li, Lei Zheng, Ying-Zheng Zhao, Cui-Tao Lu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2016

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Abstract

Brain tumor lacks effective delivery system for treatment. Focused ultrasound (FUS) can reversibly open BBB without impacts on normal tissues. As a potential drug carrier, cationic liposomes (CLs) have the ability to passively accumulate in tumor tissues for their positive charge. In this study, FUS introduced doxorubicin-loaded cationic liposomes (DOX-CLs) were applied to improve the efficiency of glioma-targeted delivery. Doxorubicin-loaded CLs (DOX-CLs) and quantum dot-loaded cationic liposomes (QD-CLs) were prepared using extrusion technology, and their characterizations were evaluated. With the advantage of QDs in tracing images, the glioma-targeted accumulation of FUS + CLs was evaluated by fluorescence imaging and flow cytometer. Cell survival rate, tumor volume, animal survival time, and brain histology in C6 glioma model were investigated to evaluate the glioma-targeted delivery of FUS + DOX-CLs. DOX-CLs and QD-CLs had suitable nanoscale sizes and high entrapment efficiency. The combined strategy of FUS introduced CLs significantly increased the glioma-targeted accumulation for load drugs. FUS + DOX-CLs showed the strongest inhibition on glioma based on glioma cell in vitro and glioma model in vivo experiments. From MRI and histological analysis, FUS + DOX-CLs group strongly suppressed the glioma progression and extended the animal survival time to 81.2 days. Among all the DOX treatment groups, FUS + DOX-CLs group showed the best cell viability and highest level of tumor apoptosis and necrosis. Combining the advantages of BBB reversible opening by FUS and glioma-targeted binding by CLs, ultrasound introduced cationic liposomes could achieve glioma-targeted delivery, which might be developed as a potential strategy for future brain tumor therapy.
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Literatur
1.
Zurück zum Zitat Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCentralCrossRefPubMed Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCentralCrossRefPubMed
2.
Zurück zum Zitat Schneider T, Mawrin C, Scherlach C, Skalej M, Firsching R (2010) Glioma in adults. Dtsch Arztebl Int 107:799–807PubMedCentralPubMed Schneider T, Mawrin C, Scherlach C, Skalej M, Firsching R (2010) Glioma in adults. Dtsch Arztebl Int 107:799–807PubMedCentralPubMed
3.
Zurück zum Zitat Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J, Auvinen A (2007) Incidence of glioma by anatomic location. Neuro Oncol 9:319–325PubMedCentralCrossRefPubMed Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J, Auvinen A (2007) Incidence of glioma by anatomic location. Neuro Oncol 9:319–325PubMedCentralCrossRefPubMed
4.
Zurück zum Zitat Liu X, Cui W, Li B, Hong Z (2012) Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles. Int J Nanomed 7:2853–2862CrossRef Liu X, Cui W, Li B, Hong Z (2012) Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles. Int J Nanomed 7:2853–2862CrossRef
5.
Zurück zum Zitat Stan AC, Casares S, Radu D, Walter GF, Brumeanu TD (1999) Doxorubicin-induced cell death in highly invasive human gliomas. Anticancer Res 19:941–950PubMed Stan AC, Casares S, Radu D, Walter GF, Brumeanu TD (1999) Doxorubicin-induced cell death in highly invasive human gliomas. Anticancer Res 19:941–950PubMed
6.
Zurück zum Zitat Walter KA, Tamargo RJ, Olivi A, Burger PC, Brem H (1995) Intratumoral chemotherapy. Neurosurgery 37:1128–1145PubMed Walter KA, Tamargo RJ, Olivi A, Burger PC, Brem H (1995) Intratumoral chemotherapy. Neurosurgery 37:1128–1145PubMed
7.
Zurück zum Zitat Voulgaris S, Partheni M, Karamouzis M, Dimopoulos P, Papadakis N, Kalofonos HP (2002) Intratumoral doxorubicin in patients with malignant brain gliomas. Am J Clin Oncol 25:60–64CrossRefPubMed Voulgaris S, Partheni M, Karamouzis M, Dimopoulos P, Papadakis N, Kalofonos HP (2002) Intratumoral doxorubicin in patients with malignant brain gliomas. Am J Clin Oncol 25:60–64CrossRefPubMed
8.
Zurück zum Zitat Laquintana V, Trapani A, Denora N, Wang F, Gallo JM, Trapani G (2009) New strategies to deliver anticancer drugs to brain tumors. Expert Opin Drug Deliv 6(10):1017–1032PubMedCentralCrossRefPubMed Laquintana V, Trapani A, Denora N, Wang F, Gallo JM, Trapani G (2009) New strategies to deliver anticancer drugs to brain tumors. Expert Opin Drug Deliv 6(10):1017–1032PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640–646CrossRefPubMed Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640–646CrossRefPubMed
10.
Zurück zum Zitat Choi JJ, Pernot M, Small SA, Konofagou EE (2007) Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. Ultrasound Med Biol 33:95–104CrossRefPubMed Choi JJ, Pernot M, Small SA, Konofagou EE (2007) Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. Ultrasound Med Biol 33:95–104CrossRefPubMed
11.
Zurück zum Zitat O’Reilly MA, Waspe AC, Ganguly M, Hynynen K (2011) Focused-ultrasound disruption of the blood–brain barrier using closely-timed short pulses: influence of sonication parameters and injection rate. Ultrasound Med Biol 37:587–594PubMedCentralCrossRefPubMed O’Reilly MA, Waspe AC, Ganguly M, Hynynen K (2011) Focused-ultrasound disruption of the blood–brain barrier using closely-timed short pulses: influence of sonication parameters and injection rate. Ultrasound Med Biol 37:587–594PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Sheikov N, McDannold N, Sharma S, Hynynen K (2008) Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol 34:1093–1104PubMedCentralCrossRefPubMed Sheikov N, McDannold N, Sharma S, Hynynen K (2008) Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. Ultrasound Med Biol 34:1093–1104PubMedCentralCrossRefPubMed
13.
Zurück zum Zitat Vlachos F, Tung Y-S, Konofagou E (2011) Permeability dependence study of the focused ultrasound-induced blood–brain barrier opening at distinct pressures and microbubble diameters using DCE-MRI. Magn Reson Med 66:8218–8230CrossRef Vlachos F, Tung Y-S, Konofagou E (2011) Permeability dependence study of the focused ultrasound-induced blood–brain barrier opening at distinct pressures and microbubble diameters using DCE-MRI. Magn Reson Med 66:8218–8230CrossRef
14.
Zurück zum Zitat Shang X, Wang P, Liu Y, Zhang Z, Xue Y (2011) Mechanism of low-frequency ultrasound in opening blood-tumor barrier by tight junction. J Mol Neurosci 43:364–369CrossRefPubMed Shang X, Wang P, Liu Y, Zhang Z, Xue Y (2011) Mechanism of low-frequency ultrasound in opening blood-tumor barrier by tight junction. J Mol Neurosci 43:364–369CrossRefPubMed
15.
Zurück zum Zitat Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K (2004) Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 30:979–989CrossRefPubMed Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K (2004) Cellular mechanisms of the blood–brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol 30:979–989CrossRefPubMed
16.
Zurück zum Zitat Hynynen K, Jolesz FA (1998) Demonstration of potential noninvasive ultrasound brain therapy through an intactskull. Ultrasound Med Biol 24:275–283CrossRefPubMed Hynynen K, Jolesz FA (1998) Demonstration of potential noninvasive ultrasound brain therapy through an intactskull. Ultrasound Med Biol 24:275–283CrossRefPubMed
17.
Zurück zum Zitat Aubry JF, Tanter M, Pernot M, Thomas JL, Fink M (2003) Experimental demonstration of noninvasive trans-skull adaptive focusing based on prior computed tomography scans. J Acoust Soc Am 113:84–93CrossRefPubMed Aubry JF, Tanter M, Pernot M, Thomas JL, Fink M (2003) Experimental demonstration of noninvasive trans-skull adaptive focusing based on prior computed tomography scans. J Acoust Soc Am 113:84–93CrossRefPubMed
18.
Zurück zum Zitat Hynynen K, McDannold N, Clement G, Jolesz FA, Zadicario E, Killiany R, Moore T, Rosen D (2006) Preclinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain-A primate study. Eur J Radiol 59:149–156CrossRefPubMed Hynynen K, McDannold N, Clement G, Jolesz FA, Zadicario E, Killiany R, Moore T, Rosen D (2006) Preclinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain-A primate study. Eur J Radiol 59:149–156CrossRefPubMed
19.
Zurück zum Zitat Goldenberg Neil M, Steinberg Benjamin E (2010) Surface charge: a key determinant of protein localization and function. Cancer Res 70:1277–1280CrossRefPubMed Goldenberg Neil M, Steinberg Benjamin E (2010) Surface charge: a key determinant of protein localization and function. Cancer Res 70:1277–1280CrossRefPubMed
20.
Zurück zum Zitat Hirko A, Tang F, Hughes JA (2003) Cationic lipid vectors for plasmid DNA delivery. Curr Med Chem 10:1185–1193CrossRefPubMed Hirko A, Tang F, Hughes JA (2003) Cationic lipid vectors for plasmid DNA delivery. Curr Med Chem 10:1185–1193CrossRefPubMed
21.
Zurück zum Zitat Bally MB, Masin D, Nayar R, Cullis PR, Mayer LD (1994) Transfer of liposomal drug carriers from the blood to the peritoneal cavity of normal and ascitic tumor-bearing mice. Cancer Chemother Pharmacol 34:137–146CrossRefPubMed Bally MB, Masin D, Nayar R, Cullis PR, Mayer LD (1994) Transfer of liposomal drug carriers from the blood to the peritoneal cavity of normal and ascitic tumor-bearing mice. Cancer Chemother Pharmacol 34:137–146CrossRefPubMed
22.
Zurück zum Zitat Huang SK, Lee KD, Hong K, Friend DS, Papahadjopolous D (1992) Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res 52:5135–5143PubMed Huang SK, Lee KD, Hong K, Friend DS, Papahadjopolous D (1992) Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res 52:5135–5143PubMed
23.
Zurück zum Zitat Huang SK, Martin FJ, Jay G, Vogel J, Papahadjopolous D, Friend DS (1993) Extravasation and transcytosis of liposomes in Kaposi’s sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. Am J Pathol 143:10–14PubMedCentralPubMed Huang SK, Martin FJ, Jay G, Vogel J, Papahadjopolous D, Friend DS (1993) Extravasation and transcytosis of liposomes in Kaposi’s sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. Am J Pathol 143:10–14PubMedCentralPubMed
25.
Zurück zum Zitat Haran G, Cohen R, Bar LK, Barenholz Y (1993) Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta 1151:201–215CrossRefPubMed Haran G, Cohen R, Bar LK, Barenholz Y (1993) Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta 1151:201–215CrossRefPubMed
26.
Zurück zum Zitat Golubenko TA (1991) Low-frequency ultrasound in the treatment of osteoarthrosis patients. Vopr Kurortol Fizioter Lech Fiz Kult 2:36–39PubMed Golubenko TA (1991) Low-frequency ultrasound in the treatment of osteoarthrosis patients. Vopr Kurortol Fizioter Lech Fiz Kult 2:36–39PubMed
27.
Zurück zum Zitat Serena T, Lee SK, Lam K, Attar P, Meneses P, Ennis W (2009) The impact of noncontact, nonthermal, low-frequency ultrasound on bacterial counts in experimental and chronic wounds. Ostomy Wound Manage 55:22–30PubMed Serena T, Lee SK, Lam K, Attar P, Meneses P, Ennis W (2009) The impact of noncontact, nonthermal, low-frequency ultrasound on bacterial counts in experimental and chronic wounds. Ostomy Wound Manage 55:22–30PubMed
28.
Zurück zum Zitat Claes L, Willie B (2007) The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol 93:384–398CrossRefPubMed Claes L, Willie B (2007) The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol 93:384–398CrossRefPubMed
29.
Zurück zum Zitat Behrens S, Daffertshofer M, Spiegel D, Hennerici M (1999) Low frequency, low-intensity ultrasound accelerates thrombolysis through the skull. Ultrasound Med Biol 25:269–273CrossRefPubMed Behrens S, Daffertshofer M, Spiegel D, Hennerici M (1999) Low frequency, low-intensity ultrasound accelerates thrombolysis through the skull. Ultrasound Med Biol 25:269–273CrossRefPubMed
30.
Zurück zum Zitat McDannold N, Vykhodtseva N, Hynynen K (2008) Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood–brain barrier disruption. Ultrasound Med Biol 34:930–937PubMedCentralCrossRefPubMed McDannold N, Vykhodtseva N, Hynynen K (2008) Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound induced blood–brain barrier disruption. Ultrasound Med Biol 34:930–937PubMedCentralCrossRefPubMed
31.
Zurück zum Zitat Kroll RA, Neuwelt EA (1998) Outwitting the blood–brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42:1083–1100CrossRefPubMed Kroll RA, Neuwelt EA (1998) Outwitting the blood–brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42:1083–1100CrossRefPubMed
32.
Zurück zum Zitat Anajafi T, Mallik S (2015) Polymersome-based drug-delivery strategies for cancer therapeutics. Ther Deliv 4:521–534CrossRef Anajafi T, Mallik S (2015) Polymersome-based drug-delivery strategies for cancer therapeutics. Ther Deliv 4:521–534CrossRef
33.
Zurück zum Zitat Tahover E, Patil YP, Gabizon AA (2015) Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: focus on liposomes. Anticancer Drugs 26:241–258CrossRefPubMed Tahover E, Patil YP, Gabizon AA (2015) Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: focus on liposomes. Anticancer Drugs 26:241–258CrossRefPubMed
34.
Zurück zum Zitat Itakura S, Hama S, Ohgita T, Kogure K (2014) Development of nanoparticles incorporating a novel liposomal membrane destabilization peptide for efficient release of cargos into cancer cells. PLoS One 9(10):111–181CrossRef Itakura S, Hama S, Ohgita T, Kogure K (2014) Development of nanoparticles incorporating a novel liposomal membrane destabilization peptide for efficient release of cargos into cancer cells. PLoS One 9(10):111–181CrossRef
35.
Zurück zum Zitat Qu MH, Zeng RF, Fang S, Dai QS, Li HP, Long JT (2014) Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer. Int J Pharm 474:112–122CrossRefPubMed Qu MH, Zeng RF, Fang S, Dai QS, Li HP, Long JT (2014) Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer. Int J Pharm 474:112–122CrossRefPubMed
36.
Zurück zum Zitat Gifford I, Vreeland W, Grdanovska S, Burgett E, Kalinich J, Vergara V, Wang CK, Maimon E, Poster D, Al-Sheikhly M (2014) Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study. Int J Radiat Biol 90:480–485CrossRefPubMed Gifford I, Vreeland W, Grdanovska S, Burgett E, Kalinich J, Vergara V, Wang CK, Maimon E, Poster D, Al-Sheikhly M (2014) Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study. Int J Radiat Biol 90:480–485CrossRefPubMed
37.
Zurück zum Zitat Zheng H, Hu Y, Huang W, de Villiers S, Pentel P, Zhang J, Dorn H, Ehrich M, Zhang C (2015) Negatively charged carbon nanohorn supported cationic liposome nanoparticles: a novel delivery vehicle for anti-nicotine vaccine. J Biomed Nanotechnol 11(12):2197–2210CrossRefPubMed Zheng H, Hu Y, Huang W, de Villiers S, Pentel P, Zhang J, Dorn H, Ehrich M, Zhang C (2015) Negatively charged carbon nanohorn supported cationic liposome nanoparticles: a novel delivery vehicle for anti-nicotine vaccine. J Biomed Nanotechnol 11(12):2197–2210CrossRefPubMed
38.
Zurück zum Zitat Tada R, Hidaka A, Iwase N, Takahashi S, Yamakita Y, Iwata T, Muto S, Sato E, Takayama N, Honjo E, Kiyono H, Kunisawa J, Aramaki Y (2015) Intranasal immunization with DOTAP cationic liposomes combined with DC-cholesterol induces potent antigen-specific mucosal and systemic immune responses in mice. PLoS one 10(10):e0139785PubMedCentralCrossRefPubMed Tada R, Hidaka A, Iwase N, Takahashi S, Yamakita Y, Iwata T, Muto S, Sato E, Takayama N, Honjo E, Kiyono H, Kunisawa J, Aramaki Y (2015) Intranasal immunization with DOTAP cationic liposomes combined with DC-cholesterol induces potent antigen-specific mucosal and systemic immune responses in mice. PLoS one 10(10):e0139785PubMedCentralCrossRefPubMed
39.
Zurück zum Zitat Dicheva BM, ten Hagen TL, Schipper D, Seynhaeve AL, van Rhoon GC, Eggermont AM, Koning GA (2014) Targeted and heat-triggered doxorubicin delivery to tumors by dual targeted cationic thermosensitive liposomes. J Control Release 10(195):37–48 Dicheva BM, ten Hagen TL, Schipper D, Seynhaeve AL, van Rhoon GC, Eggermont AM, Koning GA (2014) Targeted and heat-triggered doxorubicin delivery to tumors by dual targeted cationic thermosensitive liposomes. J Control Release 10(195):37–48
40.
Zurück zum Zitat Chaudhary AK, Yadav N, Bhat TA, O’Malley J, Kumar S, Chandra D (2015) A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy. Drug Discov Today S1359–6446:285–288 Chaudhary AK, Yadav N, Bhat TA, O’Malley J, Kumar S, Chandra D (2015) A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy. Drug Discov Today S1359–6446:285–288
Metadaten
Titel
Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes
verfasst von
Qian Lin
Kai-Li Mao
Fu-Rong Tian
Jing-Jing Yang
Pian-Pian Chen
Jie Xu
Zi-Liang Fan
Ya-Ping Zhao
Wen-Feng Li
Lei Zheng
Ying-Zheng Zhao
Cui-Tao Lu
Publikationsdatum
01.02.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 2/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2926-1

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