School of Chemistry, Indian Institute of Science Education and Research (IISER) Thiruvananthapuram, Trivandrum-695551, Kerala, India.
School of Biology, Indian Institute of Science Education and Research (IISER) Thiruvananthapuram, Trivandrum-695551, Kerala, India.
Nanoscale. 2024 Aug 29;16(34):16195-16203. doi: 10.1039/d4nr01494d.
Synergetic combination therapy is emerging as one of the most promising approaches for cancer treatment. Among the various therapeutic approaches, PDT has received particular attention due to its non-invasive nature. However, the therapeutic performance of PDT is severely affected by tumour hypoxia. Herein, we report a supramolecular strategy for the fabrication of a PDT-active 2D nanosheet loaded with a POD mimicking DNAzyme for the synergetic combination of PDT and CDT for targeted cancer therapy. Assembly of biotin-functionalized BODIPY (1) and cationic β-cyclodextrin (β-CD+) leads to the formation of a 1/β-CD+ nanosheet with positively charged β-CD+ on the surface of the sheet. The cationic face of the 1/β-CD+ sheet was then loaded with a POD-mimicking Hem-loaded G-quadruplex aptamer (Hem/DNA1) electrostatic interactions (1/β-CD+/Hem/DNA1). Cellular internalization of the 1/β-CD+/Hem/DNA1 nanosheet occurs a receptor-mediated endocytic pathway, which then undergoes lysosomal escape. Subsequently, Hem/DNA1 on the surface of 1/β-CD+/Hem/DNA1 reacts with endogenous HO the Fenton pathway to produce ˙OH and O. Moreover, under cellular conditions, Hem inside the 1/β-CD+/Hem/DNA1 nanosheet produces Fe, which then undergoes another Fenton reaction to produce ˙OH and O. The Fe generated after the Fenton reaction is then reduced to Fe by glutathione for the next Fenton cycle. At the same time, photoirradiation of the 1/β-CD+ nanosheet using a 635 nm laser produces O the PDT pathway by using endogenous O. The most remarkable feature of the present nanoformulation is the cooperativity in its therapeutic action, wherein O produced during the CDT pathway was used by the 1/β-CD+ sheet for improving its PDT efficacy in the hypoxic tumor microenvironment. This work represents a unique combination of CDT and PDT for targeted cancer therapy, wherein the CDT action of the nanoagent enhances the PDT efficacy and we strongly believe that this approach would encourage researchers to design similar combination therapy for advancements in the treatment of cancer.
协同组合疗法正成为癌症治疗最有前途的方法之一。在各种治疗方法中，由于其非侵入性，PDT 受到了特别关注。然而，PDT 的治疗效果严重受到肿瘤缺氧的影响。在此，我们报告了一种超分子策略，用于制备负载过氧化物酶模拟 DNA 酶的 PDT 活性 2D 纳米片，用于协同组合光动力治疗和细胞毒性治疗，以实现靶向癌症治疗。生物素功能化 BODIPY（1）和阳离子β-环糊精（β-CD+）的组装导致 1/β-CD+纳米片的形成，纳米片表面带有正电荷的β-CD+。然后，通过静电相互作用将过氧化物酶模拟 Hem 负载的 G-四链体适体（Hem/DNA1）负载到 1/β-CD+片的正面上（1/β-CD+/Hem/DNA1）。1/β-CD+/Hem/DNA1 纳米片通过受体介导的内吞途径进入细胞内，然后从溶酶体中逃逸。随后，表面的 Hem/DNA1 在细胞内与内源性 HO 在芬顿途径中反应生成·OH 和 O。此外，在细胞条件下，1/β-CD+/Hem/DNA1 纳米片中的 Hem 产生 Fe，然后通过另一个芬顿反应产生·OH 和 O。芬顿反应产生的 Fe 被谷胱甘肽还原为 Fe，用于下一个芬顿循环。同时，使用 635nm 激光对 1/β-CD+纳米片进行光照射，通过利用内源性 O 在 PDT 途径中产生 O。该纳米制剂的最显著特征是其治疗作用的协同性，其中 CDT 途径中产生的 O 被 1/β-CD+片用于提高其在缺氧肿瘤微环境中的 PDT 疗效。这项工作代表了针对癌症的 CDT 和 PDT 的独特结合，其中纳米剂的 CDT 作用增强了 PDT 的疗效，我们坚信这种方法将鼓励研究人员设计类似的组合疗法，以促进癌症治疗的进展。
