Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.

中文翻译：

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基质金属蛋白酶 2 反应性双载药自组装肽抑制肿瘤生长并增强乳腺癌治疗


传统的化疗药物由于缺乏靶向性和渗透性以及保留时间短而受到限制，化疗可能会诱导免疫抑制环境。肽自组装可产生特定的形态，由此产生的形态变化是对外部环境做出反应的刺激，这对于药物渗透和包封化疗药物的保留很重要。在这项研究中，成功开发了一种含有肽序列 PLGLAG 和 RGD 的多肽 （Pep1），该肽序列对基质金属蛋白酶 2 （MMP-2） 有反应。Pep1 响应 MMP-2 诱导，经历了从球形结构到高纵横比聚集体的形态转变。这种药物递送系统 （DI/Pep1） 可以同时将阿霉素 （DOX） 和吲哚美辛 （IND） 转运到靶向肿瘤细胞以进行后续药物释放，同时延长肿瘤细胞内的药物滞留，从而增加免疫原性细胞死亡并促进 CD4+ T 细胞的免疫治疗效果。最终，DI/Pep1 通过结合 DOX 和 IND 的作用减轻了肿瘤相关炎症，增强了机体的免疫反应，并抑制了乳腺癌的生长。我们的研究提供了一种有望提高癌症治疗效果的方法。