title: Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.
abstract: The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.
authors.affiliation: Department of Breast Disease Center, Shandong Cancer Hospital & Institute, Jinan, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Huo
authors.affiliation: Department of Radiotherapy, Shandong Cancer Hospital & Institute, Jinan, China.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Head and Neck Surgery, Shandong Cancer Hospital & Institute, Jinan, China.
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Department of Breast Disease Center, Shandong Cancer Hospital & Institute, Jinan, China.
authors.forename: Wen-Shu
authors.initials: WS
authors.lastname: Zuo
authors.affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: Department of Gastrointestinal Surgery, Shandong Cancer Hospital & Institute, Jinan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000627:therapeutic use; D000077341:Lapatinib; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D053758:Nanoparticles; D010587:Phagocytosis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011799:Quinazolines; D000077341:Lapatinib; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C014225:tocophersolan
keywords: apoptosis; breast cancer; drug delivery; hybrid nanoparticles; lapatinib