Details

Autor(en) / Beteiligte

• Gong, Xiang
• Zheng, Chao
• Cai, Ying
• Zhang, Wen
• Zhu, Binyu
• Rong, Rong
• Kong, Ying
• Zhang, Yuan
• Wang, Jian
• Li, Yaping
• Zhang, Pengcheng

Titel

Adenosine-modulating synthetic high-density lipoprotein for chemoimmunotherapy of triple-negative breast cancer

Ist Teil von

• Journal of controlled release, 2024-03, Vol.367, p.637-648

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Adenosine (ADO) is a common chemotherapy-associated immune checkpoint that hinders anti-tumor immunity-mediated efficacy of chemotherapy. Herein, we created a synthetic high-density lipoprotein (sHDL) by co-assembly of a doxorubicin (DOX)-apolipoprotein A1 mimetic peptide conjugate, PSB-603 (an A2BR inhibitor), phospholipid, and cholesterol oleate with a microfluidic-based method. The obtained DP-sHDL showed a self-promoted drug delivery to cancer cells via remodeling tumor microenvironment. DP-sHDL could trigger the release of ATP from cancer cells and inhibit its conversion into ADO. Consequently, DP-sHDL, while increasing immunogenic cell death, reduced intratumoral ADO levels by 58%. This treatment improved both the density and activity of CD8+ T cells as well as NK cells and relieved the immunosuppressive microenvironment, and led to a substantial inhibition of 4T1 tumor growth, thereby extending the survival of mice. The efficacy of DP-sHDL could be further improved when used in combination with immune checkpoint blockade therapy. We envision that this platform provides a simple yet promising strategy to enhance anti-tumor response of chemotherapy by relieving treatment-associated immunosuppression. [Display omitted] •DP-sHDL with DOX-ApoA-1 and PSB-603 is prepared via a microfluidic-based strategy.•DP-sHDL induces immunogenic cell death and inhibits conversion of ATP into ADO.•DP-sHDL targets SR-B1-expressing cell and remodels cancer microenvironment.•DP-sHDL synergize with αPD-L1 for chemoimmunotherapy on a murine TNBC model.