title: Crizotinib-loaded polymeric nanoparticles in lung cancer chemotherapy.
abstract: The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.
authors.affiliation: Department of Critical-Care Medicine, Qianfoshan Hospital Affiliated to Shandong University, Jinan, 250014, Shandong, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Jiang
authors.forename: Shou-Ping
authors.initials: SP
authors.lastname: Dai
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Xie
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Zhong-Hui
authors.initials: ZH
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000077547:Crizotinib; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D053758:Nanoparticles / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D013386:Succinates / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D011720:Pyrazoles; D011725:Pyridines; D013386:Succinates; C514223:poly(lactide)-tocopheryl polyethylene glycol succinate; D011092:Polyethylene Glycols; D000077547:Crizotinib