Near‐Infrared Light‐Triggered Polyprodrug/siRNA Loaded Upconversion Nanoparticles for Multi‐Modality Imaging and Synergistic Cancer Therapy
Gaizhen Kuang, Hongtong Lu, Shasha He, Hejian Xiong, Jie Yu, Qingfei Zhang, Yubin Huang
Abstract
Abstract Stimuli‐responsive nanosystems have been widely applied as effective modalities for drug/gene co‐delivery in cancer treatment. However, precise spatiotemporal manipulations of drug/gene co‐delivery, as well as multi‐modality imaging‐guided cancer therapy, still remain a daunting challenge. Here, multifunctional polyprodrug/siRNA loaded upconversion nanoparticles (UCNPs) are reported that combine computed tomography (CT), magnetic resonance (MR), and upconversion luminescence (UCL) tri‐modality imaging and near‐infrared (NIR) light‐activated drug/gene on‐demand delivery. The photoactivatable platinum(IV) (Pt(IV))‐backbone polymers (PPt) and the siRNA targeting polo‐like kinase 1 (Plk1) are loaded on the surface of polyethyleneimine (PEI)‐coated UCNPs (PUCNP) to obtain the multifunctional polyprodrug/siRNA loaded UCNPs (PUCNP@Pt@siPlk1). The PUCNP@Pt@siPlk1 can be served as a “nanotransducer” to convert NIR light (980 nm) into local ultraviolet (UV) to visible light for the cleavage of photosensitive PPt, resulting in the simultaneous on‐demand release of high toxic platinum(II) (Pt(II)) and siPlk1. Meanwhile, the PUCNP@Pt@siPlk1 has CT, T 1 ‐weighted MR, and UCL tri‐modality imaging abilities. Based on these merits, PUCNP@Pt@siPlk1 displayed excellent synergistic therapeutic efficacy via image‐guided and NIR light‐activated platinum‐based chemotherapy and RNA interfering in vitro and in vivo. Thus, this developed nanosystem with NIR light‐controlled drug/gene delivery and multi‐modality imaging abilities, will display great potential in combining chemotherapy and gene therapy.