Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, South Korea.
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2023 Jan 31;42(1):111955. doi: 10.1016/j.celrep.2022.111955. Epub 2023 Jan 4.
Delivery of cancer therapeutics to non-specific sites decreases treatment efficacy while increasing toxicity. In ovarian cancer, overexpression of the cell surface marker HER2, which several therapeutics target, relates to poor prognosis. We recently reported the assembly of biocompatible bacterial spore-like particles, termed "SSHELs." Here, we modify SSHELs with an affibody directed against HER2 and load them with the chemotherapeutic agent doxorubicin. Drug-loaded SSHELs reduce tumor growth and increase survival with lower toxicity in a mouse tumor xenograft model compared with free drug and with liposomal doxorubicin by preferentially accumulating in the tumor mass. Target cells actively internalize and then traffic bound SSHELs to acidic compartments, whereupon the cargo is released to the cytosol in a pH-dependent manner. We propose that SSHELs represent a versatile strategy for targeted drug delivery, especially in cancer settings.
将癌症治疗药物递送到非特异性部位会降低治疗效果，同时增加毒性。在卵巢癌中，细胞表面标志物 HER2 的过度表达与预后不良相关，而几种治疗药物都是针对 HER2 的。我们最近报道了一种名为“SSHELs”的生物相容性细菌孢子样颗粒的组装。在这里，我们用针对 HER2 的亲和体对 SSHELs 进行修饰，并将其与化疗药物阿霉素一起装载。与游离药物和脂质体阿霉素相比，载药 SSHELs 在小鼠肿瘤异种移植模型中可优先聚集在肿瘤组织中，从而减少肿瘤生长，提高存活率，且毒性更低。靶细胞主动内化并将结合的 SSHELs 转运到酸性隔室，随后货物以 pH 依赖性方式释放到细胞质中。我们提出，SSHELs 代表了一种用于靶向药物递送的多功能策略，特别是在癌症治疗中。
