title: Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells.
abstract: BACKGROUND
  Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells.
  
  
  RESULTS
  We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of -18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs.
  
  
  CONCLUSIONS
  These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou, 121000, P R China. shiyijie119@163.com.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: College of Veterinary Medicine, Liaoning Medical University, Jinzhou, 121000, P R China. changsu80@163.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Su
authors.affiliation: National Vaccine & Serum Institute, Beijing, 100024, China. lycuiwenyu@163.com.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Cui
authors.affiliation: Central Laboratory of Liaoning Medical University, Jinzhou, 121000, P R China. lylihongdan@163.com.
authors.forename: Hongdan
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou, 121000, P R China. lyliuliwei@163.com.
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou, 121000, P R China. lyyxfengbo@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou, 121000, P R China. lyyxliuming@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Central Laboratory of Liaoning Medical University, Jinzhou, 121000, P R China. lysurongjian@163.com.
authors.forename: Rongjian
authors.initials: R
authors.lastname: Su
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou, 121000, P R China. liangzhao79@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry*; D000077156:Gefitinib; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011799:Quinazolines / Q000008:administration & dosage*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D058973:Folate Receptors, GPI-Anchored; D011799:Quinazolines; D047392:beta-Cyclodextrins; C441457:carboxymethyl-beta-cyclodextrin; D012710:Serum Albumin, Bovine; D000255:Adenosine Triphosphate; D005492:Folic Acid; D000077156:Gefitinib