Verma Jyoti, Kumar Vishal, Wilen Carl-Eric, Rosenholm Jessica M, Bansal Kuldeep K
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering Åbo Akademi University, Biocity, Tykistökatu 6A, 20520 Turku, Finland.
Laboratory of Molecular Science and Engineering, Faculty of Science and Engineering, Åbo Akademi University, Aurum, Henrikinkatu 2, 20500 Turku, Finland.
Pharmaceutics. 2024 Sep 3;16(9):1164. doi: 10.3390/pharmaceutics16091164.
In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer-drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light.
在癌症治疗中，至关重要的是将细胞毒性药物选择性地释放到肿瘤中，以防止与抗癌药物相关的不良反应。因此，在本研究中，合成了一种对刺激敏感的聚合物 - 药物偶联物用于选择性药物释放。阿霉素（DOX）和多西他赛（DTX）通过硫代缩酮（TK）连接子偶联到新型聚（茉莉内酯）基共聚物上。此外，将一种光敏剂（叶绿素e6）连接到聚合物上，其作为活性氧生成剂来裂解TK连接子。该偶联物易于自组装成尺寸小于100 nm的胶束。当暴露于近红外（NIR）光下时，胶束对MDA - MB - 231乳腺癌细胞的细胞杀伤能力显著增强。细胞毒性的增加高于游离DOX和DTX联合使用时观察到的情况。共聚焦显微镜也证实了胶束（激光照射）释放后DOX在细胞核中的积累。在没有光照的情况下，胶束没有显示出任何毒性，而游离药物无论是否光照均具有毒性。所获得的结果表明了由外部刺激即近红外光调节的胶束的靶向药物递送潜力。
