John Garner

PLGA-amine and PEG-PLGA from PolySciTech used in development of micro-RNA based treatment for glioblastoma

Blog Post created by John Garner on May 14, 2018

Meenakshi, 2018 glioblastoma PEG-PLGA polyscitech.png

As DNA is transcribed it proceeds through an RNA (single strand) precursor which is then used to synthesize proteins. One therapeutic strategy is to find RNA counter-sequences which block the transcription for proteins of certain types (i.e. cancer-related factors) as this can reduce the growth and spread of cancer. Recently, researchers at Stanford University used PLGA-NH2 (AI010) and mPEG-PLGA (AK071) from PolySciTech (www.polyscitech.com) to develop novel brain-cancer therapy. This research holds promise for development of therapeutic strategies against this often fatal form of cancer. Read more: Meenakshi Malhotra, Thillai Veerapazham Sekar, Jeyarama S. Ananta, Rammohan Devulapally, Rayhaneh Afjei, Husam A. Babikir, Ramasamy Paulmurugan, and Tarik F. Massoud  “Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model” Oncotarget. 2018; 9:21478-21494. https://doi.org/10.18632/oncotarget.25135

 

“ABSTRACT: Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.”

 

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