title: Targeted delivery of 10-hydroxycamptothecin to human breast cancers by cyclic RGD-modified lipid-polymer hybrid nanoparticles.
abstract: Lipid-polymer hybrid nanoparticles (NPs) combining the positive attributes of both liposomes and polymeric NPs are increasingly being considered as promising candidates to carry therapeutic agents safely and efficiently into targeted sites. Herein, a modified emulsification technique was developed and optimized for the targeting lipid-polymer hybrid NPs fabrication; the surface properties and stability of the hybrid NPs were systematically investigated, which confirmed that the hybrid NPs consisted of a poly (lactide-co-glycolide) core with ∼90% surface coverage of the lipid monolayer and a ∼4.4 nm hydrated polyethylene glycol (PEG) shell. Optimization results showed that the lipid:polymer mass ratio and the lipid-PEG:lipid molar ratio could affect the size, lipid association efficiency and stability of hybrid NPs. Furthermore, a model chemotherapy drug, 10-hydroxycamptothecin, was encapsulated into hybrid NPs with a higher drug loading compared to PLGA NPs. Surface modification of the lipid layer and the PEG conjugated targeting ligand did not affect their drug release kinetics. Finally, the cytotoxicity and cellular uptake studies indicated that the lipid coverage and the c(RGDyk) conjugation of the hybrid NPs gained a significantly enhanced ability of cell killing and endocytosis. Our results suggested that lipid-polymer hybrid NPs prepared by the modified emulsion technique have great potential to be utilized as an engineered drug delivery system with precise control ability of surface targeting modification.
authors.affiliation: School of Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.forename: Xingen
authors.initials: X
authors.lastname: Luo
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D008422:Materials Testing; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D053769:Nanocapsules; D009842:Oligopeptides; D011108:Polymers; C047981:arginyl-glycyl-aspartic acid; C028098:10-hydroxycamptothecin; D002166:Camptothecin