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Title: Nanoparticulate delivery system targeted to tumor neovasculature for combined anticancer and antiangiogenesis therapy
Authors: Wang, Z.
Chui, W.-K. 
Ho, P.C. 
Keywords: angiogenesis
combination therapy
combretastatin A4
Issue Date: Mar-2011
Citation: Wang, Z., Chui, W.-K., Ho, P.C. (2011-03). Nanoparticulate delivery system targeted to tumor neovasculature for combined anticancer and antiangiogenesis therapy. Pharmaceutical Research 28 (3) : 585-596. ScholarBank@NUS Repository.
Abstract: Purpose: Herein, we designed a nanoparticulate combined delivery system decorated on the surface with RGD peptide, and encapsulating paclitaxel (PTX) and combretastatin A4 (CA4) as the respective anticancer and antiangiogenesis agent in the nanoparticle. Methods: PTX and CA4 were co-encapsulated into the biocompatible PLGA, followed by solvent evaporation to form solid nanoparticle. The cRGDfK peptide was then conjugated onto the nanoparticle surface with EDC/NHS chemistry. Results: The developed nanoparticles (NPs) were found uniform in size and well dispersed in buffers. The cellular uptake of such NPs could be efficiently detected as early as 20 min after incubation. In 24-h incubation, the encapsulated PTX could induce caspase 3/7-dependent apoptosis at 50 nM, whereas the CA4-loaded NPs could disrupt tubulin structure at 2.5 μM. The targeted dual drug-loaded nanoparticle achieved significant tumor growth suppression in vivo compared to the control from day 8 (P < 0.05). Histological results revealed that the targeted dual drug nanoparticle led to dramatic tumor vasculature disruption, significant cancer cell apoptosis and cell proliferation inhibition in the mouse model. Conclusion: These findings indicate that the targeted dual drug nanoparticulate delivery system encompassing both antiangiogenesis and anticancer effects can be a potential candidate in cancer therapy. © 2011 Springer Science+Business Media, LLC.
Source Title: Pharmaceutical Research
ISSN: 07248741
DOI: 10.1007/s11095-010-0308-2
Appears in Collections:Staff Publications

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