Journal Article

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

Huang, Yanjuan, Ren, Lingling, Wei, Qin, Jiang, Jingwen, Zhao, Chunshun, Xu, Xiaoyu, Huang, Zeqian, Dai, Xiuling, Shen, Yifeng, Guan, Zilin, Luo, Yong, Jiang, Yali, Liu, Di, Xiao, Zhanghong

2021

Overview

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.

• Publisher: Nature Publishing Group,Nature Publishing Group UK,Nature Portfolio
• Subject: 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 / 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 / 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 / Survival / Toxicity / Tumors