Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In t...

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Vydáno v:	Nature communications Ročník 12; číslo 1; s. 4310 - 22
Hlavní autoři:	Huang, Yanjuan, Guan, Zilin, Dai, Xiuling, Shen, Yifeng, Wei, Qin, Ren, Lingling, Jiang, Jingwen, Xiao, Zhanghong, Jiang, Yali, Liu, Di, Huang, Zeqian, Xu, Xiaoyu, Luo, Yong, Zhao, Chunshun
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 14.07.2021 Nature Publishing Group Nature Portfolio
Témata:	13/2 13/21 13/31 13/51 14/1 14/19 14/34 14/5 59/5 631/67/1344 631/67/1347 631/67/322/803 64/60 Animals Antitumor activity Apoptosis - drug effects B7-H1 Antigen - antagonists & inhibitors Bone cancer Bone Neoplasms - drug therapy Bone Neoplasms - immunology Bone Neoplasms - secondary Bone tumors Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - pathology Cell death Cell Line, Tumor Cell Movement - drug effects Drug Carriers - chemistry Drug delivery Drug Delivery Systems Female Humanities and Social Sciences Humans I.R. radiation Immune Checkpoint Inhibitors - therapeutic use Immune response Immune system Immunogenic Cell Death - drug effects Immunogenicity Immunologic Memory - drug effects Immunotherapy Indoles - administration & dosage Indoles - chemistry Indoles - pharmacology Infrared Rays Macrophages Macrophages - chemistry Macrophages - transplantation Medical prognosis Metastases Metastasis multidisciplinary Nanomedicine Nanotechnology Near infrared radiation Organometallic Compounds - administration & dosage Organometallic Compounds - chemistry Organometallic Compounds - pharmacology Oxaliplatin Oxaliplatin - administration & dosage Oxaliplatin - chemistry Oxaliplatin - pharmacology Patients PD-L1 protein Phenotypes Photochemotherapy - methods Photodynamic therapy Photosensitizing Agents - administration & dosage Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Prodrugs Prodrugs - administration & dosage Prodrugs - chemistry Prodrugs - pharmacology Quality of life Science Science (multidisciplinary) Survival Toxicity Tumors
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors. Bone metastases are associated with poor prognosis in patients with breast cancer and limited therapeutic options. Here the authors exploit near-infrared light responsive macrophages for the tumor-selective delivery of oxaliplatin prodrug for chemo-photodynamic therapy of primary and bone metastatic breast cancer.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-24564-0