Codelivery of dual drugs from polymeric micelles for simultaneous targeting of both cancer cells and cancer stem cells

• Published in: Nanomedicine (London, England) England), 2015-09, Vol.10 (18), p.2819-2832
• Main Authors: Krishnamurthy, Sangeetha, Ng, Victor WL, Gao, Shujun, Tan, Min-Han, Hedrick, James L, Yang, Yi Yan
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacology; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; cancer stem cells; Care and treatment; Cell Line, Tumor; Cell Proliferation - drug effects; codelivery; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Deoxycytidine - therapeutic use; Drug Carriers - chemistry; Drug Delivery Systems; Drug Synergism; efficacy; Female; gemcitabine; Humans; Lung - drug effects; Lung - pathology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Methods; Mice, Inbred BALB C; Mice, Nude; micellar nanoparticles; Micelles; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; phenformin; Phenformin - administration & dosage; Phenformin - pharmacology; Phenformin - therapeutic use; Physiological aspects; Polycarboxylate Cement - chemistry; Polyethylene Glycols - chemistry; Stem cells; Urea - analogs & derivatives
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm.15.109

Phenformin-loaded micelles (Phen M) were used in combination with gemcitabine-loaded micelles (Gem M) to study their combined effect against H460 human lung cancer cells and cancer stem cells (CSCs) and . Gem M and Phen M were prepared via self-assembly of a mixture of a diblock copolymer of PEG and urea-functionalized polycarbonate (PEG-PUC) and a diblock copolymer of PEG and acid-functionalized polycarbonate (PEG-PAC) through hydrogen bonding and ionic interactions. Gem M and Phen M were characterized and tested for efficacy both and against cancer cells and CSCs. The combination of Gem M/Phen M exhibited higher cytotoxicity against CSCs and non-CSCs than Gem M and Phen M alone, and showed significant cell cycle growth arrest . The combination therapy had superior tumor suppression and apoptosis without inducing toxicity to liver and kidney. The combination of Gem M and Phen M may be potentially used in lung cancer therapy.