Tuesday, March 16, 2021

PLGA-PEG-COOH from PolySciTech used in development of ultrasound-triggered delivery of miRNA/Gene Therapy for treatment of cancer

 

The delivery of genetic materials, RNA/DNA, to cells holds potential for the treatment of several disease states. That being said, getting these materials into the area of action is not a trivial task as endogenous RNAse and DNAse enzymes will often break them down as well as permeation across various membranes is not good. Recently researchers at Stanford University and Bracco Suisse SA use PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to create ultrasound-responsive PLGA-PEG-PEI nanoparticles to deliver RNA/Gene therapy materials to cancer cells as a treatment regimen. This research holds promise to improve therapies against cancer. Read more: Kumar, Sukumar Uday, Huaijun Wang, Arsenii V. Telichko, Arutselvan Natarajan, Thierry Bettinger, Samir Cherkaoui, Tarik F. Massoud, Jeremy J. Dahl, and Ramasamy Paulmurugan. "Ultrasound Triggered Co‐Delivery of Therapeutic MicroRNAs and a Triple Suicide Gene Therapy Vector by Using Biocompatible Polymer Nanoparticles for Improved Cancer Therapy in Mouse Models." Advanced Therapeutics: 2000197. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202000197

“Microbubbles (MBs) exhibit cavitation upon exposure to ultrasound (US), which creates opportunities to adopt them in new therapeutic approaches. The present study reports an efficient, translatable approach to precisely control the spaciotemporal delivery of therapeutic microRNAs (AmiR‐21 and miR‐100) and TK‐p53‐NTR triple therapeutic gene, co‐loaded in PLGA‐PEG‐PEI polymer nanoparticles (NPs) to tumor models of triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) using US‐mediated targeted destruction of BR38 MBs. PLGA‐PEG‐PEI conjugated triblock co‐polymer NPs are synthesized and characterized for their physicochemical properties, and optimized for co‐loading of miRNAs and TK‐p53‐NTR. Quantitative in vivo imaging and ex vivo tissue analysis of 4T1 (TNBC) subcutaneous tumors in BALB/c mice reveal 19 ± 0.5% (p < 0.01) increase in delivery of miRNAs, and 48 ± 1.79% (p < 0.001) increase in delivery of TK‐p53‐NTR upon US treatment, which results to 48 ± 6.98% (p < 0.01) reduction in tumor growth as compared to contralateral tumors without US. This significantly increases the survival rate of animals as compared to pDNA control group. Similar treatment effects are observed in both TNBC and HCC tumor models. This novel combined therapeutic approach, entailing both miRNAs and suicide gene therapy has strong potential for future applications in cancer therapy.”

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