PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Hong Sung Kim; In Ho Song; Jong Chul Kim; Eun Jeong Kim; Doo Ok Jang; Yong Serk Park Journal: J Control Release Date: 2006-08-11 Impact factor: 9.776
Authors: Rafael Rosell; Kathleen D Danenberg; Vincente Alberola; Gerold Bepler; Jose Javier Sanchez; Carlos Camps; Mariano Provencio; Dolores Isla; Miquel Taron; Pilar Diz; Angel Artal Journal: Clin Cancer Res Date: 2004-02-15 Impact factor: 12.531
Authors: Nasser Hanna; Frances A Shepherd; Frank V Fossella; Jose R Pereira; Filippo De Marinis; Joachim von Pawel; Ulrich Gatzemeier; Thomas Chang Yao Tsao; Miklos Pless; Thomas Muller; Hong-Liang Lim; Christopher Desch; Klara Szondy; Radj Gervais; Christian Manegold; Sofia Paul; Paolo Paoletti; Lawrence Einhorn; Paul A Bunn Journal: J Clin Oncol Date: 2004-05-01 Impact factor: 44.544