caa a22 4500 445312750 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0308-2 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0308-2 Nanoparticulate Delivery System Targeted to Tumor Neovasculature for Combined Anticancer and Antiangiogenesis Therapy [Elektronische Daten] [Zhe Wang, Wai-Keung Chui, Paul Ho] 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 20min after incubation. In 24-h incubation, the encapsulated PTX could induce caspase 3/7-dependent apoptosis at 50nM, whereas the CA4-loaded NPs could disrupt tubulin structure at 2.5μM. 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. Springer Science+Business Media, LLC, 2010 angiogenesis nationallicence cancer nationallicence combination therapy nationallicence combretastatin A4 nationallicence nanoparticle nationallicence paclitaxel nationallicence Wang Zhe Laboratory for Experimental and Applied Pharmacokinetics and Pharmacodynamics (LEAP2), Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Chui Wai-Keung Medicinal Chemistry Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Ho Paul Laboratory for Experimental and Applied Pharmacokinetics and Pharmacodynamics (LEAP2), Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 585-596 0724-8741 28:3<585 2011 28 11095 https://doi.org/10.1007/s11095-010-0308-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0308-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Zhe Laboratory for Experimental and Applied Pharmacokinetics and Pharmacodynamics (LEAP2), Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 700 1- Chui Wai-Keung Medicinal Chemistry Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 700 1- Ho Paul Laboratory for Experimental and Applied Pharmacokinetics and Pharmacodynamics (LEAP2), Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 585-596 0724-8741 28:3<585 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer