期刊
NANO LETTERS
卷 22, 期 11, 页码 4410-4420出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c00901
关键词
hemoglobin; protein-crowned micelle; tumor-associated macrophages; synergistic therapy; tumor microenvironment
类别
资金
- National Key Research and Development Program of China [2021YFC2400600, 2021YFC2400602]
- National Natural Science Foundation of China [51903119, 81971713]
- Guangdong Basic and Applied Basic Research Foundation [2021B1515120065]
- Guangzhou Science and Technology Bureau [202206010068]
- Zhejiang Provincial Natural Science Foundation [LZ18H180001]
The study introduces a protein-crowned micelle system for targeted and synergistic TAM reprogramming, which shows potential in enhancing cancer treatment.
Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancers, but achieving multitarget therapy of TAMs is still challenging. Here, we develop a protein-crowned micelle system for targeted and synergistic TAM reprogramming to enhance cancer treatment. The doxorubicin-loaded micelles with a hemoglobin crown (Hb-DOXM) can bind with endogenous plasma haptoglobin to realize specific M2-type TAM targeting. Under the tumor hypoxic and acidic environments, Hb-DOXM can responsively release O2 and DOX to reduce the recruitment of TAMs by hypoxia remission and release DOX to kill M2-type TAMs and cancer cells. To reprogram TAMs adequately, the TAM-modulating drug celecoxib is further encapsulated (Hb-DOXM@Cel) to repolarize M2-type TAMs. The targeted and synergistic TAM reprogramming by Hb-DOXM@Cel can remodel the tumor microenvironment (TME) to an immunostimulatory microenvironment and augment the antitumor effect of cytotoxic T lymphocyte, thus strongly enhancing the DOX-based chemotherapy. The protein-crowned micelle strategy presents a targeted and synergistic TAM therapy tool for enhanced cancer treatment.
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