Self-assembled nanoplatform for targeted delivery of chemotherapy agents via affinity-regulated molecular interactions.
Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed targeted polymeric nanoparticles called amphiphilic urethane acrylate nonionomer (UAN) for encapsulation of diverse water-insoluble drugs and diagnostic agents, as well as for simple and reproducible surface conjugation of targeting ligands. Using monoclonal antibodies or lymphocyte function-associated antigen-1 (LFA-1) I domain engineered for varying affinities to intercellular adhesion molecule (ICAM)-1, we were able to deliver UAN nanoparticles to human cancer cells with the efficiency dependent on the strength of the molecular interactions and the degree of ICAM-1 expression on cell surface. Compared to non-specific uptake of free drugs, targeted delivery of UAN nanoparticles carrying equal amount of drugs produced more potent cytotoxicity. Notably, without the targeting ligands attached, UAN nanoparticles were largely precluded from non-specific uptake by the cells, resulting in much lower toxicity. The versatility of our UAN nanoparticles in both payload encapsulation and presentation of targeting ligands may facilitate developing a robust platform for evaluating various combinations of cancer drugs and molecular interactions toward developing effective cancer therapy formulations.
Park
Spencer
S
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Kang
Sungkwon
S
Veach
Alexander J
AJ
Vedvyas
Yogindra
Y
Zarnegar
Rasa
R
Kim
Ju-Young
JY
Jin
Moonsoo M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008422:Materials Testing; D008958:Models, Molecular; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D016169:Lymphocyte Function-Associated Antigen-1; D053978:Pentacyclic Triterpenes; D011108:Polymers; D014315:Triterpenes; D018799:Intercellular Adhesion Molecule-1; C050414:celastrol