NDLI: CRGD Grafted siRNA Nano-constructs for Chemosensitization of Gemcitabine Hydrochloride in Lung Cancer Treatment

Content Provider	Springer Nature Link
Author	Khatri, Nirav Rathi, Mohan Baradia, Dipesh Misra, Ambikanandan
Copyright Year	2014
Abstract	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.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.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 IC$_{50}$ value of Gemcitabine hydrochloride 5 folds in A-549 cells compared to Gemcitabine hydrochloride alone.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.
Starting Page	806
Ending Page	818
Page Count	13
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	32
Issue Number	3
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2014-05-03
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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