State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Mol Pharm. 2023 Feb 6;20(2):1426-1434. doi: 10.1021/acs.molpharmaceut.2c01074. Epub 2023 Jan 23.
Carbon quantum dots (CDs) have attracted more and more attention in the field of biological imaging, while their applications are restricted due to their nonspecific fluorescence and small particle size. Herein, two pH-responsive carbon quantum dot-doxorubicin (DOX) conjugates were designed with maleic acid (MA, -butenedioic acid) and fumaric acid (FA, -butenedioic acid) as linker, respectively, which could self-assemble into unique hybrid micelles as tumor-specific carrier-free nanotheranostics. Owing to the acid-labile covalent modification with conjugated groups and the interaction with the surrounding DOX molecules, the fluorescence of CDs was completely quenched, while it could be recovered in the tumor intracellular microenvironment by acid-triggered cleavage of the fluorophore-drug conjugates, showing excellent turn-on fluorescence for effective cellular imaging. Especially, the conjugate with FA as linker possessed higher drug content, better drug release behavior and stronger inhibition of tumor cells than the one with MA as linker, demonstrating its promising potential as carrier-free nanotheranostics for future tumor treatment.
碳量子点（CDs）在生物成像领域引起了越来越多的关注，但其非特异性荧光和小粒径限制了其应用。本文分别以马来酸（MA，-丁烯二酸）和富马酸（FA，-丁烯二酸）作为连接体设计了两种 pH 响应性的碳量子点-阿霉素（DOX）缀合物，它们可以自组装成独特的混合胶束作为肿瘤特异性无载体纳米治疗剂。由于与共轭基团的酸不稳定共价修饰以及与周围 DOX 分子的相互作用，CDs 的荧光完全猝灭，而在肿瘤细胞内微环境中，通过荧光团-药物缀合物的酸触发裂解可以恢复荧光，从而对有效细胞成像显示出优异的开启荧光。特别是，以 FA 作为连接体的缀合物比以 MA 作为连接体的缀合物具有更高的药物含量、更好的药物释放行为和更强的肿瘤细胞抑制作用，表明其作为未来肿瘤治疗的无载体纳米治疗剂具有广阔的应用前景。
