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Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization
Small ( IF 13.0 ) Pub Date : 2023-12-14 , DOI: 10.1002/smll.202309994
Yi-Bin Liu 1 , Xia-Yun Chen 2 , Bai-Xue Yu 2 , Yi Cen 2 , Chu-Yu Huang 2 , Meng-Yi Yan 2 , Qian-Qian Liu 2 , Wei Zhang 3 , Shi-Ying Li 2 , You-Zhi Tang 1
Small ( IF 13.0 ) Pub Date : 2023-12-14 , DOI: 10.1002/smll.202309994
Yi-Bin Liu 1 , Xia-Yun Chen 2 , Bai-Xue Yu 2 , Yi Cen 2 , Chu-Yu Huang 2 , Meng-Yi Yan 2 , Qian-Qian Liu 2 , Wei Zhang 3 , Shi-Ying Li 2 , You-Zhi Tang 1
Affiliation
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A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8-CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.
中文翻译：
嵌合肽工程自传递纳米药物用于巨噬细胞极化光动力触发乳腺癌免疫治疗
迫切需要一种系统治疗策略来抑制乳腺癌快速生长和易转移的特点。在这项工作中，一种嵌合肽工程自传递纳米药物（称为 ChiP-CeR）用于通过巨噬细胞极化进行光动力触发乳腺癌免疫治疗。其中，ChiP-CeR由氯e6光敏剂（Ce6）和拉米喹莫特TLR7/8激动剂（R837）组成，并进一步用肿瘤基质靶向肽（Fmoc-K(Fmoc)-PEG 8 -CREKA修饰） ChiP-CeR通过特异性识别纤连蛋白主动积聚在肿瘤部位，通过光动力疗法（PDT）消除原发肿瘤的生长，同时，原发肿瘤的破坏会触发免疫原性细胞死亡（ICD）效应的释放。此外，ChiP-CeR还可以将高迁移率组box-1（HMGB1）和暴露钙网蛋白（CRT）极化为M1型TAM，组合起来可以激活T细胞抗肿瘤免疫。总体而言，ChiP-CeR 对原发性和肺转移性肿瘤具有优异的抗肿瘤作用，这为转移性乳腺癌的系统治疗提供了适用的纳米药物和可行的策略。
更新日期：2023-12-14
中文翻译：
嵌合肽工程自传递纳米药物用于巨噬细胞极化光动力触发乳腺癌免疫治疗
迫切需要一种系统治疗策略来抑制乳腺癌快速生长和易转移的特点。在这项工作中，一种嵌合肽工程自传递纳米药物（称为 ChiP-CeR）用于通过巨噬细胞极化进行光动力触发乳腺癌免疫治疗。其中，ChiP-CeR由氯e6光敏剂（Ce6）和拉米喹莫特TLR7/8激动剂（R837）组成，并进一步用肿瘤基质靶向肽（Fmoc-K(Fmoc)-PEG 8 -CREKA修饰） ChiP-CeR通过特异性识别纤连蛋白主动积聚在肿瘤部位，通过光动力疗法（PDT）消除原发肿瘤的生长，同时，原发肿瘤的破坏会触发免疫原性细胞死亡（ICD）效应的释放。此外，ChiP-CeR还可以将高迁移率组box-1（HMGB1）和暴露钙网蛋白（CRT）极化为M1型TAM，组合起来可以激活T细胞抗肿瘤免疫。总体而言，ChiP-CeR 对原发性和肺转移性肿瘤具有优异的抗肿瘤作用，这为转移性乳腺癌的系统治疗提供了适用的纳米药物和可行的策略。
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