PEG-PLGA and PLGA from PolySciTech used for mechanistic study of nanoparticle binding to tumor tissue
PolySciTech
division of Akina, Inc. (www.polyscitech.com)
provides a wide array of biodegradable polymers and biodegradable block
copolymers for research applications. Recently, researchers at the University
of Maryland utilized mPEG-PLGA 5K-10K (PolyVivo Cat# AK010) and PLGA (PolyVivo
AP081) to generate nanoparticles and then tracked these nanoparticles in
regards to their uptake into tumor cells as compared to their non-specific
binding towards extracellular matrix and other biological components. They
found that PEG plays an important role in preventing non-specific binding. This
research holds promise for improved therapeutic delivery strategies. Read more:
Dancy, Jimena G., Aniket S. Wadajkar, Craig S. Schneider, Joseph RH Mauban,
Olga G. Goloubeva, Graeme F. Woodworth, Jeffrey A. Winkles, and Anthony J. Kim.
"Non-specific binding and steric hindrance thresholds for penetration of
particulate drug carriers within tumor tissue." Journal of Controlled
Release (2016). http://www.sciencedirect.com/science/article/pii/S0168365916304692
“Abstract:
Therapeutic nanoparticles (NPs) approved for clinical use in solid tumor
therapy provide only modest improvements in patient survival, in part due to
physiological barriers that limit delivery of the particles throughout the
entire tumor. Here, we explore the thresholds for NP size and surface
poly(ethylene glycol) (PEG) density for penetration within tumor tissue
extracellular matrix (ECM). We found that NPs as large as 62 nm, but less
than 110 nm in diameter, diffused
rapidly within a tumor ECM preparation (Matrigel) and breast tumor xenograft
slices ex vivo. Studies of PEG-density revealed that increasing PEG density
enhanced NP diffusion and that PEG density below a critical value led to
adhesion of NP to ECM. Non-specific binding of NPs to tumor ECM components was
assessed by surface plasmon resonance (SPR), which revealed excellent
correlation with the particle diffusion results. Intravital microscopy of NP
spread in breast tumor tissue confirmed a significant difference in tumor
tissue penetration between the 62 and 110 nm PEG-coated NPs, as well as between
PEG-coated and uncoated NPs. SPR assays also revealed that Abraxane, an
FDA-approved non-PEGylated NP formulation used for cancer therapy, binds to
tumor ECM. Our results establish limitations on the size and surface PEG
density parameters required to achieve uniform and broad dispersion within
tumor tissue and highlight the utility of SPR as a high throughput method to
screen NPs for tumor penetration. Graphical abstract: Nanoparticle (NP)
penetration was visualized via intravital microscopy after direct injection
into flank tumors. Uncoated NPs were immobilized at the tumor injection site
and densely PEG-coated NPs as large as 63 nm penetrated into the tumor. Keywords:
Nanoparticles; PEG density; Tumor tissue penetration; Surface plasmon resonance
(SPR); Multiple particle tracking (MPT); Intravital microscopy”
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