用于成像引导增强肿瘤光疗的可编程刺激响应碳点-纳米凝胶杂化材料
Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.
机构信息
International Joint Research Center for Photo-Responsive Molecules and Materials, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.
Cixi Institute of Biomedical Engineering, Chinese Academy of Science (CAS), Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, Ningbo 315201, China.
出版信息
ACS Appl Mater Interfaces. 2022 Mar 2;14(8):10142-10153. doi: 10.1021/acsami.2c00174. Epub 2022 Feb 17.
For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.
为了协调纳米诊疗剂在增强肿瘤积累和穿透方面的矛盾,提高细胞内化效率和快速消除是促进其临床应用的关键策略。本文设计了可编程刺激响应型聚异丙基丙烯酰胺-碳点(PNIPAM-CD)杂化纳米凝胶来解决上述冲突。PNIPAM-CDs 的粒径增大使其能够有效地提高其在肿瘤部位的积累。一旦杂化纳米凝胶在肿瘤部位结合并暴露于近红外光(660nm)照射下,碳点会产生热和活性氧(ROS),从而激活光热治疗(PTT)和光动力治疗(PDT)效应,同时诱导部分降解 PNIPAM-CDs 以实现深层组织穿透。此外,由于 PNIPAM-CDs 的 pH 响应电荷反转和温度依赖的亲水性/疏水性转换特性,可以实现功能成分的增强细胞内化。最后,肿瘤细胞中超表达的谷胱甘肽(GSH)会触发部分降解的杂化纳米凝胶的进一步裂解,有利于其从体内快速清除。这项工作不仅提出了一种使用单一功能成分(即多功能碳点)制备纳米诊疗剂的新策略,简化了制备过程,而且通过克服多种生物屏障有效将药物递送到肿瘤细胞中,提高了治疗效果,降低了副作用。