Hypoxia-Responsive Polymersomes for Drug Delivery to Hypoxic Pancreatic Cancer Cells.
Hypoxia in tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, diblock copolymer poly(lactic acid)-azobenzene-poly(ethylene glycol), which self-assembles to form polymersomes in an aqueous medium. The polymersomes did not release any encapsulated contents for 50 min under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 min. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28%, respectively. We used three-dimensional spheroid cultures of pancreatic cancer cells BxPC-3 to demonstrate hypoxia-mediated release of the drugs from the polymersomes. The vesicles were nontoxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have potential for future applications in imaging and treatment of hypoxic tumors.
Department of Pharmaceutical Sciences and ‡Department of Physics and Mathematics, North Dakota State University , Fargo, North Dakota 58102, United States.
Prajakta
P
Kulkarni
Department of Pharmaceutical Sciences and ‡Department of Physics and Mathematics, North Dakota State University , Fargo, North Dakota 58102, United States.
Manas K
MK
Haldar
Department of Pharmaceutical Sciences and ‡Department of Physics and Mathematics, North Dakota State University , Fargo, North Dakota 58102, United States.
Seungyong
S
You
Department of Pharmaceutical Sciences and ‡Department of Physics and Mathematics, North Dakota State University , Fargo, North Dakota 58102, United States.
Yongki
Y
Choi
Department of Pharmaceutical Sciences and ‡Department of Physics and Mathematics, North Dakota State University , Fargo, North Dakota 58102, United States.
Sanku
S
Mallik
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D004337:Drug Carriers; D011108:Polymers; D003841:Deoxycytidine; D004317:Doxorubicin; D000093542:Gemcitabine