Chitosan hybrid nanoparticles as a theranostic platform for targeted doxorubicin/VEGF shRNA co-delivery and dual-modality fluorescence imaging†

Yang, Hong, Xu, Min, Li, Shun, Shen, Xue, Li, Tingting, Yan, Jie, Zhang, Chengchen, Wu, Chunhui, Zeng, Hongjuan and Liu, Yiyao (2016) Chitosan hybrid nanoparticles as a theranostic platform for targeted doxorubicin/VEGF shRNA co-delivery and dual-modality fluorescence imaging†. RSC Advances, 6 (35), 29685-29696. (doi:10.1039/c6ra03843c).

Abstract

The current strategies for drug/gene and multimodal imaging probes integrated into a single nanoparticle have some limitations still. Here, multifunctional chitosan hybrid nanoparticles (denoted as FA–CS–FITC(DOX/C-dots)/VEGF shRNA) containing folic acid (FA), fluorescein isothiocyanate (FITC) and doxorubicin (DOX)/carbon quantum dots (C-dots)/VEGF shRNA were fabricated as a targeted drug/gene co-delivery nanovector for potential cancer therapy and fluorescence imaging. The self-assembled FA–CS–FITC(DOX/C-dots)/VEGF shRNA nanocomplexes exhibited a desirable and homogenous particle size (154 24 nm), moderate positive charges (23.2 1.8 mV) and superior stability. The nanocomplexes without noteworthy cytotoxicity are capable of delivering VEGF shRNA into human cervical cancer HeLa cells with high efficiency while effectively protecting shRNA from degradation by exogenous DNase I and nucleases. The release behavior of DOX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.5, and also presented a pH-triggered release profile. Confocal microscopy analysis confirmed that both FA-targeted function and FA-enhanced buffering capacity induced high transfection, specific cellular uptake and efficient intracellular delivery of FA–CS–FITC(DOX/C-dots)/VEGF shRNA nanocomplexes in folate receptor-overexpressed HeLa cells. Transfected HeLa cells exhibited significantly decreased VEGF expression, inhibited cell proliferation, and increased cell apoptosis, which led to synergistic antitumor activities. Furthermore, the nanocomplexes demonstrated excellent dual fluorescence cellular imaging at a modest concentration. This work indicates that the integrated theranostic design of FA–CS–FITC(DOX/C-dots)/ VEGF shRNA nanocomplexes potentially allows for the image-guided and target-specific treatment of cancer.

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Contributors

Author: Chengchen Zhang

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