title: cRGD grafted siRNA nano-constructs for chemosensitization of gemcitabine hydrochloride in lung cancer treatment.
abstract: OBJECTIVE
  The aim of present investigation was to effectively deliver ribonucleotide reductase subunit 1 (RRM1) targeted siRNA and assess chemo-sensitization of lung cancer cells against Gemcitabine hydrochloride. It was hypothesised that effective and selective delivery of RRM1 siRNA will help in the treatment of lung cancer chemotherapy using Gemcitabine hydrochloride by reducing drug dose and thereby, reduces dose related toxicity of Gemcitabine hydrochloride.
  
  
  METHODS
  In this investigation, cRGD grafted siRNA nano-constructs were developed for efficient and targeted intracellular delivery of siRNA. Developed formulations were characterized for gel retardation assay, particle size, zeta potential, cryo transmission electron microscopy, serum stability, in vitro cytotoxicity, qualitative and quantitative cell uptake, gene expression, and chemo-sensitization.
  
  
  RESULTS
  Complete complexation of siRNA with cRGD grafted nano-constructs was found at N/P ratio of 2.0. Naked siRNA was found to degrade within 6 h in presence of 50% serum while nano-constructs protected the complexed siRNA even after 24 h. RRM1 level significantly reduced when siRNA was delivered in nano-construct form as compared to naked siRNA. Pre-exposure of RRM1 siRNA decreased the IC50 value of Gemcitabine hydrochloride 5 folds in A-549 cells compared to Gemcitabine hydrochloride alone.
  
  
  CONCLUSIONS
  These results suggest the application of present siRNA delivery strategy to potentiate the chemotherapeutic effect by means of chemosensitization which may be utilized for effective and thorough remission of lung cancer.
authors.affiliation: Pharmacy Department, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, 390001, Gujarat, India.
authors.forename: Nirav
authors.initials: N
authors.lastname: Khatri
authors.forename: Mohan
authors.initials: M
authors.lastname: Rathi
authors.forename: Dipesh
authors.initials: D
authors.lastname: Baradia
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D010316:Particle Size; D010456:Peptides, Cyclic / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C507169:cyclic arginine-glycine-aspartic acid peptide; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine