Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, 150025, China.
Key Laboratory of Molecular Cytogenetics and Genetic Breeding of Heilongjiang Province, College of Life Science and Technology, Harbin Normal University, Harbin 150025, China.
Biomater Sci. 2023 May 2;11(9):3128-3143. doi: 10.1039/d3bm00124e.
Carbon dots (CDs) have great potential for cancer diagnosis and treatment. Photodynamic therapy and chemodynamic therapy are promising treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive, having no multi-drug resistance, and having no systemic toxic side effects. However, the tumor microenvironment (TME) and poor targetability often reduce the therapeutic effect. In this work, we have successfully prepared folate-based carbon dots (FCP-CDs) from folic acid (FA), citric acid (CA), and polyethyleneimine (PEI) for tumor-targeting. The surface of FCP-CDs was modified using organic disulfide, 3,3'-dithiodipropionic acid (DTPA), and a photosensitizer (PS) pyropheophorbide-a (PPa) to form a tumor microenvironment-responsive nanoplatform, FCP-CDs@DTPA@PPa (named FCPPD), for synergistic cancer therapy. The results showed that FCPPD effectively preserved the tumor target specificity of folic acid and the photodynamic therapeutic (PDT) activity of PPa, and could provide additional chemodynamic therapeutic (CDT) function by reacting with hydrogen peroxide (HO) to generate ˙OH. The introduction of DTPA, which contains disulfide bonds, endows FCPPD with an excellent ability to deplete glutathione (GSH) in tumors intracellular redox reactions, amplifying intracellular oxidative strain and enhancing ROS-based therapeutic effects. Systematic and studies under various conditions have shown that the obtained FCPPD nanoparticles have good biocompatibility and could be a promising therapeutic agent for imaging-guided PDT/CDT combination therapy.
碳点（CDs）在癌症诊断和治疗方面具有巨大的潜力。基于活性氧物种（ROS）的光动力疗法和化学动力学疗法是很有前途的治疗方法，它们具有微创、无多药耐药性和无系统毒性副作用的优点。然而，肿瘤微环境（TME）和靶向性差常常会降低治疗效果。在这项工作中，我们成功地从叶酸（FA）、柠檬酸（CA）和聚乙烯亚胺（PEI）制备了基于叶酸的碳点（FCP-CDs），用于肿瘤靶向。FCP-CDs 的表面用有机二硫代、3,3'-二硫代二丙酸（DTPA）和光敏剂（PS）焦脱镁叶绿酸-a（PPa）进行修饰，形成肿瘤微环境响应的纳米平台，FCP-CDs@DTPA@PPa（命名为 FCPPD），用于协同癌症治疗。结果表明，FCPPD 有效地保留了叶酸的肿瘤靶向特异性和 PPa 的光动力治疗（PDT）活性，并通过与过氧化氢（HO）反应生成˙OH 提供额外的化学动力学治疗（CDT）功能。DTPA 的引入，其中包含二硫键，赋予 FCPPD 一种优异的能力，可在肿瘤内还原反应中耗尽谷胱甘肽（GSH），放大细胞内氧化应激并增强基于 ROS 的治疗效果。在各种条件下进行的系统研究表明，所得到的 FCPPD 纳米粒子具有良好的生物相容性，可能是一种有前途的用于成像引导 PDT/CDT 联合治疗的治疗剂。
