Faculty of Chemistry, Northeast Normal University, Changchun, 130024, P.R. China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
Adv Healthc Mater. 2021 Oct;10(20):e2100938. doi: 10.1002/adhm.202100938. Epub 2021 Jul 3.
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 -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.
刺激响应型纳米系统已被广泛应用于癌症治疗中的药物/基因共递送来提高疗效。然而，精确的药物/基因共递送时空调控以及多模态成像引导的癌症治疗仍然是一个艰巨的挑战。本研究报告了一种多功能前药/siRNA 负载上转换纳米颗粒（UCNPs），它结合了计算机断层扫描（CT）、磁共振（MR）和上转换发光（UCL）三模态成像以及近红外（NIR）光按需激活药物/基因递释。光活化的顺铂（IV）（Pt（IV））-主链聚合物（PPt）和针对丝氨酸/苏氨酸激酶 1（Plk1）的 siRNA 被负载在聚乙二胺（PEI）包覆的 UCNPs（PUCNP）表面，得到多功能前药/ siRNA 负载 UCNPs（PUCNP@Pt@siPlk1）。PUCNP@Pt@siPlk1 可以作为“纳米转导器”，将近红外光（980nm）转换为局部紫外（UV）至可见光，以裂解光敏感的 PPt，从而按需同时释放高毒性的铂（II）（Pt（II））和 siPlk1。同时，PUCNP@Pt@siPlk1 具有 CT、T -加权 MR 和 UCL 三模态成像能力。基于这些优点，PUCNP@Pt@siPlk1 通过图像引导和 NIR 光激活的基于铂的化学疗法和 RNA 干扰在体外和体内显示出优异的协同治疗效果。因此，这种具有 NIR 光控药物/基因递释和多模态成像能力的纳米系统，将在联合化疗和基因治疗方面显示出巨大的潜力。
