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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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; pp. 4310 - 22
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 14.07.2021
Nature Publishing Group
Nature Portfolio
Subjects:
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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
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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
Online Access:Get full text
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24564-0