title: Co-delivery of Gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance.
abstract: BACKGROUND
  Acquired drug resistance is becoming common during cancer chemotherapy and leads to treatment failure in clinic. To conquer acquired drug resistance, nanotechnology has been employed to deliver drug. In this paper, we prepared chitosan nanoparticles (CS NPs) capable of entrapping Gefitinib and chloroquine (CQ) for multiple drugs combinational therapy.
  
  
  RESULTS
  The results showed that Gefitinib/CQ-NPs were characterized of small particle size about 80.8 ± 9.7 nm and positive zeta potential about 21.3 ± 1.56 mV, and drug controlled to release slowly on a biphasic pattern. Compared with free Gefitinib and Gefitinib loaded NPs, Gefitinib and CQ co-delivery by CS nanoparticles showed the higher inhibition rates and enhanced cell apoptosis. Through western blot analysis, we found that Gefitinib could promote LC3 expression, which is the marker of autophagosomes. So, the acquired drug resistance may be associated with autophagy. CQ as an inhibitor of autophagolysosomes formation could overcome autophagy in the resistant cells.
  
  
  CONCLUSIONS
  These findings demonstrated that chitosan nanoparticles entrapping Gefitinib and chloroquine have the potential to overcome acquired resistance and improve cancer treatment efficacy, especially towards resistant strains. Graphical abstract: Cellular distribution of NPs after incubating QGY (a) and QGY/Gefitinib cells (b) with rhodamine B-labeled NPs.
authors.affiliation: School of Materials Science and Engineering, School of Life Sciences, Tianjin University, Tianjin, 300072, People's Republic of China. liangzhao79@163.com.|School of Pharmacy, Liaoning Medical University, Jinzhou, 121000, People's Republic of China. liangzhao79@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Oncology, BenQ Medical Center, Nanjing Medical University, Nanjing, 210029, People's Republic of China. yangguang9002@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Liaoning Medical University, Jinzhou, 121000, People's Republic of China. shiyijie119@163.com.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Veterinary Medicine, Liaoning Medical University, Jinzhou, 121000, People's Republic of China. changsu80@163.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Su
authors.affiliation: School of Materials Science and Engineering, School of Life Sciences, Tianjin University, Tianjin, 300072, People's Republic of China. jinchang@tju.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D002738:Chloroquine / Q000494:pharmacology*; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009336:Necrosis; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D011799:Quinazolines; D002738:Chloroquine; D000255:Adenosine Triphosphate; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate; D000077156:Gefitinib