Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Seoburo 2066, Suwon, Gyeonggi 16419, Republic of Korea.
Biomedical and Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro Wonmi-gu, Bucheon, Gyeonggi 14662, Republic of Korea.
Biomater Sci. 2023 Jun 27;11(13):4652-4663. doi: 10.1039/d3bm00635b.
-NT (-NT) is an anaerobic bacterium that can be used for targeted cancer therapy because it germinates selectively in the hypoxic regions of tumor tissues. However, systemic administration of -NT spores cannot effectively treat tumors because of the limited intratumoral delivery of active spores. In this study, we demonstrated that multifunctional porous microspheres (MPMs) containing -NT spores have the potential for image-guided local tumor therapy. The MPMs can be repositioned under an external magnetic field, enabling precise tumor targeting and retention. Polylactic acid-based MPMs were prepared using the oil-in-water emulsion technique and then coated with a cationic polyethyleneimine polymer prior to loading with negatively charged -NT spores. The -NT spores delivered by MPMs were released and germinated in a simulated tumor microenvironment, effectively secreting proteins cytotoxic to tumor cells. In addition, the germinated -NT induced immunogenic death of the tumor cells and M1 polarization of macrophages. These results indicate that MPMs encapsulated with -NT spores have great potential for image-guided cancer immunotherapy.
-NT（-NT）是一种厌氧菌，可用于靶向癌症治疗，因为它会在肿瘤组织的缺氧区域选择性发芽。然而，由于活性孢子在肿瘤内的输送有限，全身给予 -NT 孢子不能有效地治疗肿瘤。在这项研究中，我们证明了含有 -NT 孢子的多功能多孔微球（MPM）具有图像引导局部肿瘤治疗的潜力。MPM 可以在外磁场下重新定位，实现精确的肿瘤靶向和保留。聚乳酸基 MPM 是使用油包水乳液技术制备的，然后用阳离子聚乙烯亚胺聚合物涂覆，然后负载带负电荷的 -NT 孢子。MPM 递送的 -NT 孢子在模拟肿瘤微环境中释放并发芽，有效地分泌对肿瘤细胞具有细胞毒性的蛋白质。此外，发芽的 -NT 诱导肿瘤细胞免疫原性死亡和巨噬细胞 M1 极化。这些结果表明，封装 -NT 孢子的 MPM 具有用于图像引导癌症免疫治疗的巨大潜力。
