Wednesday, February 12, 2014

Mal-PEG-PLA for cancer treatment

Polyscitech (www.polyscitech.com) provides several types of activated Maleimide-PEG-PLA (PolyVivo AI50, AI60, etc.). Recently this kind of polymer has shown promise when conjugated to APRPG peptide for targeted delivery of nanoparticles to ovarian cancer cells. Read more at: Wang, Yunfei, Peifeng Liu, Yourong Duan, Xia Yin, Qi Wang, Xiaofei Liu, Xinran Wang et al. "Specific cell targeting with APRPG conjugated PEG–PLGA nanoparticles for treating ovarian cancer." Biomaterials 35, no. 3 (2014): 983-992. http://dx.doi.org/10.1016/j.biomaterials.2013.09.062


“ABSTRACT: Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)–poly (lactic acid) (PEG–PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG–PLA and mPEG–PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ΞΆ-potential (−14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.” 

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