Nanoparticle-mediated p53 gene therapy for tumor inhibition.

Drug Delivery and Translational Research
B SharmaV Labhasetwar

Abstract

The p53 tumor suppressor gene is mutated in 50% of human cancers, resulting in more aggressive disease with greater resistance to chemotherapy and radiation therapy. Advances in gene therapy technologies offer a promising approach to restoring p53 function. We have developed polymeric nanoparticles (NPs), based on poly (lactic-co-glycolic acid), that provide sustained intracellular delivery of plasmid DNA, resulting in sustained gene expression without vector-associated toxicity. Our previous studies with p53 gene-loaded NPs (p53NPs) demonstrated sustained antiproliferative effects in cancer cells in vitro. The objective of this study was to evaluate the efficacy of p53NPs in vivo. Tumor xenografts in mice were established with human p53-null prostate cancer cells. Animals were treated with p53NPs by either local (intratumoral injection) or systemic (intravenous) administration. Controls included saline, p53 DNA alone, and control NPs. Mice treated with local injections of p53NPs demonstrated significant tumor inhibition and improved animal survival compared with controls. Tumor inhibition corresponded to sustained and greater p53 gene and protein expression in tumors treated with p53NPs than with p53 DNA alone. A single intrav...Continue Reading

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Citations

Jun 27, 2013·Nanomedicine·Isaac M AdjeiVinod Labhasetwar
Nov 12, 2013·Advances in Chronic Kidney Disease·Chris Brede, Vinod Labhasetwar
Feb 23, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabienne DanhierVéronique Préat
Mar 22, 2016·ACS Applied Materials & Interfaces·Arunkumar RengarajYun Suk Huh
Jan 22, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Natalia BarkalinaKevin Coward
Dec 3, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tanmoy SadhukhaSwayam Prabha
Feb 1, 2017·Journal of Drug Targeting·Fathia Zaki El SharkawiLaila Ahmed Rashed
May 1, 2019·Diseases·Kenneth Lundstrom
Jul 5, 2018·Diseases·Chiaki Hidai, Hisataka Kitano
Jul 14, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Kishor SarkarKaushik Chatterjee
Feb 1, 2013·Molecular Cancer Therapeutics·Chandrashekhar D KamatChristine L Hann
Sep 10, 2019·Bioconjugate Chemistry·Sudipta SenapatiPralay Maiti

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