Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, PR China.
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy.
ACS Nano. 2024 Jul 9;18(27):18046-18057. doi: 10.1021/acsnano.4c05216. Epub 2024 Jun 27.
Tumor metastasis remains a major challenge in cancer management. Among various treatment strategies, immune cell-based cancer therapy holds a great potential for inhibiting metastasis. However, its wide application in cancer therapy is restricted by complex preparations, as well as inadequate homing and controllability. Herein, we present a groundbreaking approach for bioorthogonally manipulating tumor-NK (natural killer) cell assembly to inhibit tumor metastasis. Multiple dibenzocyclootyne (DBCO) groups decorated long single-stranded DNA were tail-modified on core-shell upconversion nanoparticles (CSUCNPs) and condensed by photosensitive chemical linker (PC-Linker) DNA to shield most of the DBCO groups. On the one hand, the light-triggered DNA scaffolds formed a cross-linked network by click chemistry, effectively impeding tumor cell migration. On the other hand, the efficient cellular assembly facilitated the effective communication between tumor cells and NK-92 cells, leading to enhanced immune response against tumors and further suppression of tumor metastasis. These features make our strategy highly applicable to a wide range of metastatic cancers.
肿瘤转移仍然是癌症治疗的主要挑战。在各种治疗策略中，基于免疫细胞的癌症治疗对于抑制转移具有很大的潜力。然而，其在癌症治疗中的广泛应用受到复杂的制备、不足的归巢和可控性的限制。在此，我们提出了一种开创性的方法，通过生物正交操纵肿瘤-NK（自然杀伤）细胞组装来抑制肿瘤转移。在核壳上转换纳米粒子（CSUCNPs）上修饰了多个二苯并环辛炔（DBCO）基团的长单链 DNA 通过光敏感化学连接子（PC-Linker）DNA 进行尾部修饰，以屏蔽大部分 DBCO 基团。一方面，光触发的 DNA 支架通过点击化学形成交联网络，有效阻止肿瘤细胞迁移。另一方面，有效的细胞组装促进了肿瘤细胞与 NK-92 细胞之间的有效通讯，导致对肿瘤的免疫反应增强，并进一步抑制肿瘤转移。这些特点使我们的策略非常适用于广泛的转移性癌症。
