Blog dedicated to answering technical questions in an open format relating to PolySciTech (A division of Akina, Inc.) products.
Monday, May 14, 2018
PLGA-amine and PEG-PLGA from PolySciTech used in development of micro-RNA based treatment for glioblastoma
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) 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.
(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.”
BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology
Center, West Lafayette, IN) is a free, 1-day scientific networking conference
hosted by Akina, Inc. See more BPCRconference.com