期刊
ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 13, 页码 14887-14902出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c23274
关键词
palmitic acid modified human serum albumin; tumor microenvironment; tumor-associated macrophages; metastasis; safety
资金
- National Natural Science Foundation of China, China [82173758, 81690261]
- Sichuan major science and technology project on biotechnology and medicine, China [2018SZDZX0018]
THP-PSA NPs exhibit stronger cytotoxicity against 4T1 and M2 macrophages compared with THP-HSA NPs in vitro. In vivo, MDSCs infiltration and immunosuppressive cytokines secretion significantly decrease after effective elimination of TAMs through THP-PSA NPs treatment, accompanied by an increase in immunostimulatory cytokine expression.
Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment (TME), profoundly affect the occurrence and development of tumors. To overcome the common limitations of TAMS-targeted delivery systems, such as off-target toxicity, high cost, and transformation probability, we fabricated pirarubicin (THP)-loaded palmitic acid modified human serum albumin nanoparticles (THP-PSA NPs) for dual-targeting of tumor cells and TAMs via acidic secretory proteins rich in cysteine (SPARC) and scavenger receptor-A (SR-A), respectively. In vitro, the THP-PSA NPs exhibit stronger cytotoxicity against 4T1 and M2 macrophages compared with THP-loaded human serum albumin nanoparticles (THP-HSA NPs). In vivo, the infiltration of myeloid-derived suppressor cells (MDSCs) and the secretion of immunosuppressive cytokines significantly decrease after effective elimination of the TAMs through the THP-PSA NPs treatment; this is accompanied by an increase in the immunostimulatory cytokine expression level. Moreover, the antitumor and antimetastasis experimental results indicate that the tumor volumes in mice treated with the THP-PSA NPs are effectively controlled, resulting in an inhibition rate of 81.0% and almost no metastases in the lung tissues. Finally, in terms of biological safety, the THP-PSA NPs perform similar to THP-HSA NPs, causing no damage to the liver or kidney.
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