title: Amphiphilic hyper-branched co-polymer nanoparticles for the controlled delivery of anti-tumor agents.
abstract: In this investigation, we have designed and synthesized an amphiphilic co-polymer with hyper-branched poly(amine-ester) and polylactide (HPAE-co-PLA) to generate nanoparticles (NPs). These have been used to encapsulate a highly active hydrophobic anti-tumor agent, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT). Encapsulation in NPs was done in an effort to increase the anti-tumor activity of this agent by facilitating its delivery to tumor cells. We have also examined and optimized the formulation parameters of the NPs that alter their drug-loading capacity and their physical, chemical and biological properties. The resulting NPs exhibited high Bp4eT-loading capacity and substantial stability in aqueous solution. In vitro drug release studies demonstrated a controlled drug release profile with increased release at acidic pH. Anti-tumor proliferation assays showed that both free drug and drug-encapsulated NPs markedly inhibited tumor cell proliferation in a time- and concentration-dependent manner. Direct microscopic observation revealed that the fluorescent NPs were taken up by cells and localized, in part, in organelles consistent with lysosomes. These results demonstrate a feasible application of the amphiphilic hyper-branched co-polymer, HPAE-co-PLA, as nanocarriers for intracellular delivery of potent anti-tumor agents.
authors.affiliation: National Center for Nanoscience and Technology of China, Beijing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Miao
authors.forename: Dongxue
authors.initials: D
authors.lastname: Xu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Tiewei
authors.initials: T
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: David B
authors.initials: DB
authors.lastname: Lovejoy
authors.forename: Danuta S
authors.initials: DS
authors.lastname: Kalinowski
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008422:Materials Testing; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers