Retracted: Multifunctional Polymeric Nanosystems for Dual‐Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors

Abstract

Combination of antiangiogenesis and chemotherapy holds vast promise for effective inhibition of tumor proliferation and invasion. Herein, a multifunctional self-assembled nanosystem consisting of amphiphilic c(RGDyK)-functionalized low-molecular-weight heparin-gambogic acid conjugate (cRHG) is developed, using c(RGDyK) peptide as αv β3 integrin targeting moiety to realize a double-targeted delivery to both tumor cells and angiogenic vasculature. cRHG with a markedly decreased anticoagulant activity can self-assemble into nanosized particles (around 150 nm). cRHG nanoparticles effectively inhibit vascular endothelial growth factor (VEGF)-triggered tube-like formation of HUVEC and neovascularization of subcutaneous Matrigel plugs. More importantly, the targeting ability of cRHG nanoparticles is revealed by their efficient internalization by αv β3 integrin-positive cells (U87MG and HUVEC) in vitro and obvious accumulation of Cy7/cRHG in the tumor site with strong fluorescence signals in both cancer cells and neovasculature. Besides, cRHG maintains the in vitro cytotoxic activity of gambogic acid, while achieving the highest in vivo antitumor activity in U87MG mouse xenograft model and displaying better safety profile than free drugs solutions. Mechanistic investigations reveal the substantial inhibition of hypoxia-inducible factor-1 alpha, VEGF, and CD31 expression by cRHG nanoparticles with remarkable down-regulation of VEGFR2 phosphorylation. These results suggest that cRHG nanoparticles provide a versatile nanoplatform for efficacious combinatorial tumor therapy.

Synchronized Ratiometric Codelivery of Metformin and Topotecan through Engineered Nanocarrier Facilitates In Vivo Synergistic Precision Levels at Tumor Site

“…Accounting to the dissimilar pharmacokinetic profiles of individual drugs, meager penetration, and heterogeneous distribution, the redemption of actual synergistic ratios at the target site confronted issues to realize the ultimate therapeutic effect of the regimen . To mitigate the problems associated with free drug combination therapy, nanoparticles have formulated to coload synergistic drug combinations . Delivery of synergistic drug ratios through nanocarriers provides controlled, temporal, and spatial delivery of multiple cargos, enables drug accumulation in tumor, and releases the drugs at a synchronized rate, thereby, probability of maintenance of intracellular synergistic drug concentrations is possible.…”

A Tumor Vascular‐Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

“…Efficient nanoparticle uptake in the targeted cells is important for VP, AQ4N, and siHIF‐1α to exert their activity, as all their targets locate inside the cells. We then evaluated the uptake of the nanocarrier, using the VP as the fluorescent probe, in human umbilical vein endothelial cells (HUVECs) or PC‐3 cells, both of which highly express integrin α v β 3 . As expected, c(RGDfK) peptides improved the nanoparticle uptake in HUVECs and PC‐3 cells at both low (10 µg mL −1 ) and high (50 µg mL −1 ) nanoparticle concentrations, conferring the dual‐targeting property (Figure F,G).…”

Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer

“…This formulation showed considerable inhibition of VEGF, hypoxia inducible factor-1 alpha, and CD31 expression with significant downregulation of pVEGFR2. These results offer a versatile nanoplatform for efficient combinatorial tumor therapy [105]. In a similar study, nanopolymer was developed for targeted co-delivery of multiple anticancer and antiangiogenic agents using LyP-1 peptide as a targeting ligand [106].…”