Tuesday, October 21, 2014

Mal-PEG-PLA for generation of CLT1 targeted nanoparticles as treatment for brain cancer

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers including reactive endcapped maleimide-PEG-PLA and PLGA type copolymers. The maleimide functionality allows for conjugation to thiol in pH neutral aqeous solution allowing for peptide/protein conjugation. Recently this was utilized to generate a nanoparticle which has a peptide targeting moiety towards brain cancer cells. It was found that this nanoparticle successfully delivered chemotherapeutic paclitaxel to these cells in mouse test. Read more: Zhang, Bo, Shun Shen, Ziwei Liao, Wei Shi, Yu Wang, Jingjing Zhao, Yue Hu et al. "Targeting fibronectins of glioma extracellular matrix by CLT1 peptide-conjugated nanoparticles." Biomaterials 35, no. 13 (2014): 4088-4098. http://www.sciencedirect.com/science/article/pii/S0142961214000623

“Abstract: The abundant extracellular matrix (ECM) in the glioma microenvironment play a critical role in the maintenance of glioma morphology, glioma cells differentiation and proliferation, but little has been done to understand the feasibility of ECM as the therapeutic target for glioma therapy. In this study, a drug delivery system targeting fibronectins (FNs), a prevailing component in the ECM of many solid tumors, was constructed for glioma therapy based on the interaction between the abundant FNs in glioma tissues and the FNs-targeting moiety CLT1 peptide. CLT1 peptide was successfully conjugated to PEG-PLA nanoparticles (CNP). FNs were demonstrated to be highly expressed in the ECM of glioma spheroids in vitro and glioma tissues in vivo. CLT1 modification favored targeting nanoparticles penetration into the core of glioma spheroids and consequently induced more severe inhibitive effects on glioma spheroids growth than traditional NP. In vivo imaging, ex vivo imaging and glioma tissue slides showed that CNP enhanced nanoparticles retention in glioma site, distributed more extensively and more deeply into glioma tissues than that of conventional NP, and mainly located in glioma cells rather than in extracellular matrix as conventional NP. Pharmacodynamics outcomes revealed that the median survival time of glioma-bearing mice models treated with paclitaxel-loaded CNP (CNP-PTX) was significantly prolonged when compared with that of any other group. TUNEL assay demonstrated that more extensive cell apoptosis was induced by CNP-PTX treatment compared with other treatments. Altogether, these promising results indicated that this ECM-targeting drug delivery system enhanced retention and glioma cell uptake of nanoparticles and might have a great potential for glioma therapy in clinical applications. Keywords: Extracellular matrix; Fibronectin; Targeting; Nanoparticles; Glioma; Retention”
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