title: Synergistic co-delivery of doxorubicin and paclitaxel using multi-functional micelles for cancer treatment.
abstract: The main purposes of this study are to demonstrate the synergistic anticancer drug systems with the combined doxorubicin (D) and paclitaxel (P) via the aid of cell penetrating and cell targeting moieties for enhancing the cancer therapeutic effect. Firstly, the synergistic effect of combined free drugs (D/P) was investigated to obtain the suitable dose combination for subsequent studies. The combination of free drugs D/P at molar ratio of 1/0.2 shows synergistic therapeutic effect compared with the treatment of a free single drug D or P. Secondly, sustainable release systems of two single drug-loaded micelles, (i) co-delivered D-FOL micelle & P-FOL micelle system and (ii) co-delivered D-TAT/FOL micelle & P-TAT/FOL micelle system, at D/P molar ratio of 1/0.2 were investigated. The results show synergistic effect with the higher efficacy of the TAT/FOL system compared to FOL only system. Finally, a dual D/P-loaded system with sustainable release rate, synergistic drug interaction, selective targeting to cancer cells and high cell penetrating ability was designed. The D/P-TAT/FOL micelles exhibit an IC50 value of 0.172 μM D/0.043 μM P, which is much lower than the IC50 values of the single drug-loaded micelles without functionalization (3.873 μM for D-micelles and 0.790 μM for P-micelles). Overall, this newly developed dual encapsulation of D and P in the multifunctional carrier would be a promising technology for cancer treatment.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
authors.forename: Hoang Hanh Phuoc
authors.initials: HH
authors.lastname: Duong
authors.forename: Lin-Yue Lanry
authors.initials: LY
authors.lastname: Yung
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers; D004357:Drug Synergism; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D012995:Solubility / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D010446:Peptide Fragments; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus; D004317:Doxorubicin; D005492:Folic Acid; D017239:Paclitaxel
keywords: Doxorubicin; Dual drug synergy; FOL; Paclitaxel; TAT