title: Targeted Biomimetic Nanoparticles for Synergistic Combination Chemotherapy of Paclitaxel and Doxorubicin.
abstract: Codelivery of multiple chemotherapeutics has become a versatile strategy in recent cancer treatment, but the antagonistic behavior of combined drugs limited their application. We developed a recombinant high-density lipoprotein (rHDL) nanoparticle for the precise coencapsulation and codelivery of two established drugs and hypothesized that they could act synergistically to improve anticancer efficacy. The coloaded rHDL was formulated by passively incorporating hydrophobic paclitaxel (PTX), and subsequently remotely loading hydrophilic doxorubicin (Dox) into the same nanoparticles. The resultant rHDL system restored targeted delivery function toward cancer cells via scavenger receptor class B (SR-BI), as confirmed by in vitro confocal imaging and flow cytometry. These coloaded rHDL nanoparticles were remarkably effective in increasing the ratiometric accumulation of drugs in cancer cells and enhancing antitumor response at synergistic drug ratios. In particular, they exhibited more efficacious anticancer effects in an in vitro cytotoxicity evaluation and in a xenograft tumor model of hepatoma compared with free drug cocktail solutions. These results confirm that the coloaded rHDL nanoparticles are promising candidates for the synergistic delivery of drugs with diverse physicochemical properties in cancer treatment integrating efficiency and safety considerations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Rui
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Yuanrong
authors.identifier: 0000-0002-7778-5737
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jiangsu University , Zhenjiang 212013, People's Republic of China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry; D032701:Biomimetics / Q000379:methods; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004357:Drug Synergism; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008075:Lipoproteins, HDL; D004317:Doxorubicin; D017239:Paclitaxel
keywords: codelivery high-density lipoprotein; combination antitumor chemotherapy; doxorubicin; paclitaxel; ratio dependent synergy; synergistic effect