Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers
Tumor-Targeted Drug and CpG Delivery System for Phototherapy and Docetaxel-Enhanced Immunotherapy with Polarization toward M1-Type Macrophages on Triple Negative Breast Cancers
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用于三阴性乳腺癌光疗和多西紫杉醇增强免疫治疗的肿瘤靶向药物和 CpG 递送系统，并针对 M1 型巨噬细胞进行极化
DOI：
10.1002/adma.201904997
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发表时间：
2019-11-13
影响因子：
29.4
通讯作者：
Dong, Chunyan
中科院分区：
文献类型：
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作者：
Chen, Lv;Zhou, Lulu;Dong, Chunyan
近年来，由于控制转移性疾病的潜力，癌症免疫治疗已经取得了有希望的临床反应。然而，由于乳腺癌的PD-L1表达有限、细胞毒性T淋巴细胞（CTL）浸润较低、髓源性抑制细胞（MDSC）水平较高，因此证明免疫治疗对乳腺癌的上级治疗效果优于黑色素瘤和非小细胞肺癌的研究有限。本文中，成功开发了用于协同光疗（包括光动力疗法（PDT）、光热疗法（PTT））和多西他赛（DTX）增强的免疫疗法的多功能纳米平台（FA-CuS/DTX@PEI-PpIX-CpG纳米复合物，表示为FA-CD@PP-CpG）。在650和808 nm的照射下，纳米复合材料表现出优异的PDT功效和光热转换能力。更重要的是，基于4 T1荷瘤小鼠模型，FA‐CD@PP‐CpG在体内可显著抑制肿瘤生长，且无明显副作用。FA-CD @ PP-CpG中负载的低剂量DTX可以促进CTL的浸润，以提高抗PD-L1抗体（aPD-L1）的效力，抑制MDSC，并有效地将MDSC向M1表型转化，以降低肿瘤负荷，进一步增强抗肿瘤效力。总之，FA‐CD@PP‐CpG纳米复合物在多西他赛增强的免疫疗法中为乳腺癌的临床应用提供了有效的协同治疗模式。
Cancer immunotherapy has achieved promising clinical responses in recent years owing to the potential of controlling metastatic disease. However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non‐small‐cell lung cancer because of its limited expression of PD‐L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid‐derived suppressor cells (MDSCs). Herein, a multifunctional nanoplatform (FA‐CuS/DTX@PEI‐PpIX‐CpG nanocomposites, denoted as FA‐CD@PP‐CpG) for synergistic phototherapy (photodynamic therapy (PDT), photothermal therapy (PTT) included) and docetaxel (DTX)‐enhanced immunotherapy is successfully developed. The nanocomposites exhibit excellent PDT efficacy and photothermal conversion capability under 650 and 808 nm irradiation, respectively. More significantly, FA‐CD@PP‐CpG with no obvious side effects can remarkably inhibit the tumor growth in vivo based on a 4T1‐tumor‐bearing mice modal. A low dosage of loaded DTX in FA‐CD@PP‐CpG can promote infiltration of CTLs to improve efficacy of anti‐PD‐L1 antibody (aPD‐L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy. Taken together, FA‐CD@PP‐CpG nanocomposites offer an efficient synergistic therapeutic modality in docetaxel‐enhanced immunotherapy for clinical application of breast cancer.