期刊
ACS NANO
卷 15, 期 3, 页码 4636-4646出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c08996
关键词
photoinduced shrinkable nanocarrier; deep tumor penetration; phototriggered drug release; cancer chemoimmunotherapy; targeting the soil and the seed strategy
类别
资金
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [51773067, 51822302]
- Program for Guangdong Introducing innovative and Enterpreneurial Teams [2017ZT07S054]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2017B030306002]
- Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
- High-level Hospital Construction Project [DFJH201905]
- Fundamental Research Funds for the Central Universities
- Open Project of Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education [2020ZD04]
The study developed a novel nanocarrier that can differentially target tumor cells and tumor-associated macrophages, showing promising therapeutic effects.
This nanocarrier can shrink under light exposure, releasing drugs to achieve deeper tumor penetration and better anti-tumor effects.
Simultaneously targeting tumor cells and nonmalignant cells represent a more efficient strategy for replacing the traditional method of targeting only tumor cells, and co-delivery nanocarriers have inherent advantages to achieve this goal. However, differential delivery of multiple agents to various types of cell with different spatial distribution patterns remains a large challenge. Herein, we developed a nanocarrier of platinum(IV) prodrug and BLZ-945, BLZ@S-NP/Pt, to differentially target tumor cells and tumor-associated macrophages (TAMs). The BLZ@S-NP/Pt undergoes shrinkage to small platinum(IV) prodrug-conjugating nanoparticles under 660 nm light, resulting in deep tumor penetration to kill more cancer cells. Meanwhile, such shrinkage also enables the rapid release of BLZ-945 in the perivascular regions of tumor to preferentially deplete TAMs (enriched in perivascular regions). Therefore, BLZ@S-NP/Pt differentially and precisely delivers agents to TAMs and tumor cells located in different spatial distribution, respectively, eventually having synergistic anticancer effects in multiple tumor models.
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