Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 311121 Hangzhou, P. R. China.
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6618-6623. doi: 10.1073/pnas.1902029116. Epub 2019 Mar 20.
Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy.
尽管基于铂的抗癌药物在癌症治疗中占主导地位，但由于严重的副作用以及它们对耐药性癌症的无效性，其临床应用受到限制。光动力疗法（PDT）和化学疗法的精确结合可以协同提高治疗效果，从而通过多管齐下的攻击来克服耐药性。在此，我们利用离散的有机铂（II）金属笼（M）的明确定义的空腔来包裹八乙基卟啉（OEP），一种光敏剂，形成双功能化系统 M⊃OEP，该系统被包裹在由两亲性嵌段共聚物自组装成的纳米颗粒（MNPs）的疏水性核心中。通过无铜点击反应，将靶向配体接枝在 MNPs 的表面上，旨在将化疗药物和光敏剂特异性递送到癌细胞中。得益于增强的通透性和保留效应以及主动靶向能力，实现了 MNPs 的高肿瘤积累，从而提高了治疗效果并降低了副作用。体内研究表明，化疗和 PDT 的联合治疗对耐药性肿瘤模型表现出优异的抗肿瘤性能，这归因于它们协同的抗癌功效。
