title: Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment.
abstract: BACKGROUND
  Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers.
  
  
  OBJECTIVE
  This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues.
  
  
  METHODS
  In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line.
  
  
  RESULTS
  PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity.
  
  
  CONCLUSIONS
  The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.
authors.affiliation: a Department of Pharmacy , Shandong Provincial Hospital Affiliated to Shandong University , Ji'nan , People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: b Department of Internal Medicine Oncology , Shandong Tumor Hospital and Institute , Ji'nan , People's Republic of China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Li
authors.affiliation: a Department of Pharmacy , Shandong Provincial Hospital Affiliated to Shandong University , Ji'nan , People's Republic of China.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Shen
authors.affiliation: c Department of Pharmacy , Shandong Tumor Hospital and Institute , Ji'nan , People's Republic of China.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b Department of Internal Medicine Oncology , Shandong Tumor Hospital and Institute , Ji'nan , People's Republic of China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhao
authors.affiliation: b Department of Internal Medicine Oncology , Shandong Tumor Hospital and Institute , Ji'nan , People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Department of Pharmacy , Shandong Provincial Hospital Affiliated to Shandong University , Ji'nan , People's Republic of China.
authors.forename: Dongna
authors.initials: D
authors.lastname: Zou
authors.affiliation: d Department of Pharmacy , The Hospital Pharmacy, Maternal and Child Health Care of Zaozhuang , Zaozhuang , People's Republic of China, and.
authors.forename: Zhenfa
authors.initials: Z
authors.lastname: Gao
authors.affiliation: e Department of Pharmacy , The Second Hospital of Shandong University , Ji'nan , People's Republic of China.
authors.forename: Chunwen
authors.initials: C
authors.lastname: Yue
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016190:Carboplatin / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D055752:Small Cell Lung Carcinoma / Q000737:chemistry / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D016190:Carboplatin; D017239:Paclitaxel
keywords: Carboplatin; combination chemotherapy; non-small cell lung cancer; paclitaxel; prodrug-based nano-drug delivery system