Targeted delivery of cisplatin to tumor xenografts via the nanoparticle component of nano-diamino-tetrac

• Published in: Nanomedicine (London, England) England), 2017-02, Vol.12 (3), p.195-205
• Main Authors: Sudha, Thangirala, Bharali, Dhruba J, Yalcin, Murat, Darwish, Noureldien HE, Coskun, Melis Debreli, Keating, Kelly A, Lin, Hung-Yun, Davis, Paul J, Mousa, Shaker A
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bladder; Bladder cancer; Cancer therapies; Cell Culture Techniques; Cell cycle; Cell Line, Tumor; Cell Survival; Chemotherapy; cisplatin; Cisplatin - administration & dosage; Cisplatin - chemistry; Cisplatin - pharmacology; Deoxyribonucleic acid; DNA; Drug Delivery Systems; Drug dosages; Drug efficacy; Drug Liberation; Female; Gene expression; Heterografts; Humans; integrin; Integrin alphaVbeta3 - metabolism; Kinases; Lactic Acid - chemistry; Lung cancer; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; nanotetrac; NDAT; Neoplasm Transplantation; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Particle Size; Polyglactin 910; Polyglycolic Acid - chemistry; Polymers; Polyvinyl alcohol; Proteins; Surface Properties; tetraiodothyroacetic acid; Thyroid gland; Thyroxine - analogs & derivatives; Tumors; urinary bladder carcinoma; Urinary Bladder Neoplasms - drug therapy
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm-2016-0315

Nano-diamino-tetrac (NDAT) targets a receptor on integrin αvβ3; αvβ3 is generously expressed by cancer cells and dividing endothelial cells and to a small extent by nonmalignant cells. The tetrac (tetraiodothyroacetic acid) of NDAT is covalently bound to a poly(lactic-co-glycolic acid) nanoparticle that encapsulates anticancer drugs. We report NDAT delivery efficiency of cisplatin to agent-susceptible urinary bladder cancer xenografts. Cisplatin-loaded NDAT (NDAT-cisplatin) was administered to xenograft-bearing nude mice. Tumor size response and drug content were measured. Intratumoral drug concentration was up to fivefold higher (p < 0.001) in NDAT-cisplatin-exposed lesions than with conventional systemic administration. Tumor volume reduction achieved was NDAT-cisplatin > NDAT without cisplatin > cisplatin alone. NDAT markedly enhances cisplatin delivery to urinary bladder cancer xenografts and increases drug efficacy.