We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Targeted nanomaterials for radiotherapy

    Freddy E Escorcia

    Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY 10021, USA.

    ,
    Michael R McDevitt

    Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY 10021, USA.

    ,
    Carlos H Villa

    Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY 10021, USA.

    &
    David A Scheinberg

    † Author for correspondence

    Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY 10021, USA.

    Published Online:https://doi.org/10.2217/17435889.2.6.805

    Nanomaterials have garnered increasing interest recently as potential therapeutic drug-delivery vehicles. Among the existing nanomaterials are the pure carbon-based particles, such as fullerenes and nanotubes, various organic dendrimers, liposomes and other polymeric compounds. These vehicles have been decorated with a wide spectrum of target-reactive ligands, such as antibodies and peptides, which interact with cell-surface tumor antigens or vascular epitopes. Once targeted, these new nanomaterials can then deliver radioisotopes or isotope generators to the cancer cells. Here, we will review some of the more common nanomaterials under investigation and their current and future applications as drug-delivery scaffolds with particular emphasis on targeted cancer radiotherapy.

    Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

    Bibliography

    • Jemal A, Siegel R, Ward E et al.: Cancer statistics. CA Cancer J. Clin.57(1),43–66 (2007).
    • Mathers CD, Loncar D: Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med.3(11),e442 (2006).
    • Jain RK: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science307(5706),58–62 (2005).•• Good review describing antiangiogenic therapy-dependent ‘vascular normalization’
    • Iyer AK, Khaled G, Fang J, Maeda H: Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov. Today11(17–18),812–818 (2006).
    • Duda DG, Batchelor TT, Willett CG, Jain RK: VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects. Trends Mol. Med.13(6),223–230 (2007).
    • Singh Jaggi J, Henke E, Seshan SV et al.: Selective α-particle mediated depletion of tumor vasculature with vascular normalization. PLoS ONE2,e267 (2007).• Description of actinium-225-based antiangiogenic radioimmunotherapy with evidence of vascular normalization as a means of improving delivery of subsequent chemotherapeutics.
    • Folkins C, Man S, Xu P et al.: Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res.67(8),3560–3564 (2007).
    • Sengupta S, Eavarone D, Capila I et al.: Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature436(7050),568–572 (2005).• Authors present a novel ‘nanocell’ which allows a temporal release of two distinct drugs, an antiangiogenic agent along with a chemotherapeutic.
    • Jang BS, Lim E, Hee Park S et al.: Radiolabeled high affinity peptidomimetic antagonist selectively targets α(v)β(3) receptor-positive tumor in mice. Nucl. Med. Biol.34(4),363–370 (2007).
    • 10  Beck R, Seidl C, Pfost B et al.: (213)Bi-radioimmunotherapy defeats early-stage disseminated gastric cancer in nude mice. Cancer Sci.98(8),1215–1222 (2007).
    • 11  Felding-Habermann B, Lerner RA, Lillo A et al.: Combinatorial antibody libraries from cancer patients yield ligand-mimetic Arg-Gly-Asp-containing immunoglobulins that inhibit breast cancer metastasis. Proc. Natl Acad. Sci. USA101(49),17210–17215 (2004).
    • 12  Eklund JW, Kuzel TM: Denileukin diftitox: a concise clinical review. Expert Rev. Anticancer Ther.5(1),33–38 (2005).
    • 13  Dearling JL, Pedley RB: Technological advances in radioimmunotherapy. Clin. Oncol. (R. Coll. Radiol.)19(6),457–469 (2007).
    • 14  McDevitt MR, Ma D, Lai LT et al.: Tumor therapy with targeted atomic nanogenerators. Science294(5546),1537–1540 (2001).•• Landmark paper describing effective cancer radioimmunotherapy with the potent α-particle emitter actinium-225
    • 15  McDevitt MR, Barendswaard E, Ma D et al.: An α-particle emitting antibody ([213Bi] J591) for radioimmunotherapy of prostate cancer. Cancer Res.60(21),6095–6100 (2000).
    • 16  Jurcic JG, Larson SM, Sgouros G et al.: Targeted α-particle immunotherapy for myeloid leukemia. Blood100(4),1233–1239 (2002).
    • 17  Mulford DA, Jurcic JG: Antibody-based treatment of acute myeloid leukaemia. Expert Opin. Biol. Ther.4(1),95–105 (2004).
    • 18  Li Y, Tian Z, Rizvi SM, Bander NH, Allen BJ: In vitro and preclinical targeted α-therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen. Prostate Cancer Prostatic Dis.5(1),36–46 (2002).
    • 19  Larson SM, Nelp WB: Radiopharmacology of a simplifield technetium-99m-colloid preparation for photoscanning. J. Nucl. Med.7(11),817–826 (1966).
    • 20  Kam NW, O'Connell M, Wisdom JA, Dai H: Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc. Natl Acad. Sci. USA102(33),11600–11605 (2005).
    • 21  DeNardo SJ, DeNardo GL, Natarajan A et al.: Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF-induced thermoablative therapy for human breast cancer in mice. J. Nucl. Med.48(3),437–444 (2007).• Targeted alternating magnetic field-induced thermoablative cancer therapy
    • 22  Maier-Hauff K, Rothe R, Scholz R et al.: Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme. J. Neurooncol.81(1),53–60 (2007).
    • 23  Lapotko DO, Lukianova E, Oraevsky AA: Selective laser nano-thermolysis of human leukemia cells with microbubbles generated around clusters of gold nanoparticles. Lasers Surg. Med.38(6),631–642 (2006).
    • 24  Toth E, Bolskar RD, Borel A et al.: Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents. J. Am. Chem. Soc.127(2),799–805 (2005).
    • 25  Zakharian TY, Seryshev A, Sitharaman B et al.: A fullerene-paclitaxel chemotherapeutic: synthesis, characterization, and study of biological activity in tissue culture. J. Am. Chem. Soc.127(36),12508–12509 (2005).
    • 26  Ashcroft JM, Tsyboulski DA, Hartman KB et al.: Fullerene (C60) immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody. Chem. Commun. (Camb.)28,3004–3006 (2006).
    • 27  Sayes CM, Marchione AA, Reed KL, Warheit DB: Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles. Nano Lett.7(8),2399–2406 (2007).
    • 28  Cagle DW, Kennel SJ, Mirzadeh S, Alford JM, Wilson LJ: In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers. Proc. Natl Acad. Sci. USA96(9),5182–7 (1999).• One of the early papers describing in vivo biodistribution of water-soluble fullerenes.
    • 29  Liu Z, Cai W, He L et al.: In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat. Nano2(1),47–52 (2007).•• Best example of noncovalent carbon nanotube (CNT) modification for in vivo tumor targeting.
    • 30  Li Z, Hulderman T, Salmen R et al.: Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ. Health Perspect.115(3),377–382 (2007).
    • 31  Zhang LW, Zeng L, Barron AR, Monteiro-Riviere NA: Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes. Int. J. Toxicol.26(2),103–113 (2007).
    • 32  Raja PM, Connolley J, Ganesan GP et al.: Impact of carbon nanotube exposure, dosage and aggregation on smooth muscle cells. Toxicol. Lett.169(1),51–63 (2007).
    • 33  Singh R, Pantarotto D, Lacerda L et al.: Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc. Natl Acad. Sci. USA103(9),3357–3362 (2006).• One of first papers describing in vivo handling of water-soluble CNTs.
    • 34  McDevitt MR, Chattopadhyay D, Kappel BJ et al.: Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes. J. Nucl. Med.48(7),1180–1189 (2007).•• Covalent modification of CNTs to achieve specific tumor targeting in vivo.
    • 35  Guo J, Zhang X, Li Q, Li W: Biodistribution of functionalized multiwall carbon nanotubes in mice. Nucl. Med. Biol.34(5),579–583 (2007).
    • 36  McDevitt MR, Chattopadhyay D, Jaggi JS et al.: PET imaging of soluble yttrium-86-labeled carbon nanotubes in mice. PLoS ONE (2007) (In Press).
    • 37  Khan MK, Nigavekar SS, Minc LD et al.: In vivo biodistribution of dendrimers and dendrimer nanocomposites – implications for cancer imaging and therapy. Technol. Cancer Res. Treat.4(6),603–613 (2005).
    • 38  Esfand R, Tomalia DA: Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov. Today6(8),427–436 (2001).
    • 39  Patri AK, Kukowska-Latallo JF, Baker JR Jr: Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv. Drug Deliv. Rev.57(15),2203–2214 (2005).
    • 40  Duncan R, Izzo L: Dendrimer biocompatibility and toxicity. Adv. Drug Deliv. Rev.57(15),2215–2237 (2005).
    • 41  Malik N, Wiwattanapatapee R, Klopsch R et al.: Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.J. Control. Release65(1–2),133–148 (2000).
    • 42  Lesniak WG, Kariapper MS, Nair BM et al.: Synthesis and characterization of PAMAM dendrimer-based multifunctional nanodevices for targeting αvβ3 integrins. Bioconjug. Chem.18(4),1148–1154 (2007).
    • 43  Backer MV, Gaynutdinov TI, Patel V et al.: Vascular endothelial growth factor selectively targets boronated dendrimers to tumor vasculature. Mol. Cancer Ther.4(9),1423–1429 (2005).
    • 44  Hong S, Leroueil PR, Majoros IJ et al.: The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem. Biol.14(1),107–115 (2007).• Description of the advantages that nanoparticle multivalency might provide as drug-delivery systems.
    • 45  Koyama Y, Talanov VS, Bernardo M et al.: A dendrimer-based nanosized contrast agent dual-labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice. J. Magn Reson. Imaging25(4),866–871 (2007).•• Describes the synthesis and application of a versatile dendrimer-based magnetic resonance (MR)/near-infrared (NIR) optical imaging agent for the detection of sentinel lymph node.
    • 46  Shukla R, Thomas TP, Peters JL et al.: HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb. Bioconjug. Chem.17(5),1109–1115 (2006).•• Specific targeting of HER2-expressing tumors with anti-HER2-mAb conjugated dendrimer.
    • 47  Patri AK, Myc A, Beals J et al.: Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy. Bioconjug. Chem.15(6),1174–1181 (2004).• Example of antibody-conjugated dendrimer constructs.
    • 48  Okuda T, Kawakami S, Akimoto N et al.: PEGylated lysine dendrimers for tumor-selective targeting after intravenous injection in tumor-bearing mice. J. Control. Release116(3),330–336 (2006).
    • 49  Kobayashi H, Kawamoto S, Bernardo M et al.: Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging. J. Control. Release111(3),343–51 (2006).• Describes dendrimer-based MR imaging agents and a generation-dependent improvement on lymphatic system visualization.
    • 50  Le UM, Cui Z: Long-circulating gadolinium-encapsulated liposomes for potential application in tumor neutron capture therapy. Int. J. Pharm.312(1–2),105–112 (2006).
    • 51  Barth RF, Coderre JA, Vicente MG, Blue TE: Boron neutron capture therapy of cancer: current status and future prospects. Clin. Cancer Res.11(11),3987–4002 (2005).
    • 52  Gupta B, Torchilin VP: Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U-87 MG tumor xenografts in nude mice. Cancer Immunol. Immunother.56(8),1215–1223 (2007).
    • 53  Sofou S, Thomas JL, Lin HY et al.: Engineered liposomes for potential α-particle therapy of metastatic cancer. J. Nucl. Med.45(2),253–260 (2004).
    • 54  Cuenca AG, Jiang H, Hochwald SN et al.: Emerging implications of nanotechnology on cancer diagnostics and therapeutics. Cancer107(3),459–466 (2006).
    • 55  Jin C, Wu H, Liu J, Bai L, Guo G: The effect of paclitaxel-loaded nanoparticles with radiation on hypoxic MCF-7 cells. J. Clin. Pharm. Ther.32(1),41–47 (2007).
    • 56  Duncan R: Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer6(9),688–701 (2006).• Good review of polymer conjugates currently used clinically as well as those that hold promise for future clinical use.
    • 57  Jaggi JS, Seshan SV, McDevitt MR et al.: Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys. Int. J. Radiat. Oncol. Biol. Phys.64(5),1503–1512 (2006).
    • 58  Rolleman EJ, Forrer F, Bernard B et al.: Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [(177)Lu-DOTA (0), Tyr(3)] octreotate. Eur. J. Nucl. Med. Mol. Imaging34(5),763–771 (2007).