A homologous-targeting "nanoconverter" with variable size for deep tumor penetration and immunotherapy.

Abstract

Tumor-associated immunosuppression, as a key barrier, prevents immunotherapy-resistant tumors. In this study, an ingenious "nanoconverter" was designed to convert immunosuppression into immunoactivation, which was a C6-ceramide (C6)-modified tumor cytomembrane-coated polydopamine-paclitaxel system (PTX/PDA@M-C6). The co-administration of C6-ceramide and tumor cytomembrane changed an adaptive immune state to an activation state, which induced a robust antigen presentation ability of tumor-infiltrating dendritic cells to activate T1 helper cells and cytotoxic T lymphocytes. Meanwhile, C6-ceramide regulated the phenotype of macrophages via the reactive oxygen species pathway, which resulted in the conversion of M2-like macrophages by infiltration within tumors into M2-like macrophages, and therefore, M2-like macrophage-mediated immunosuppression was weakened distinctly. The "nanoconverter"-mediated conversion process upregulated the expression of related immune factors including interleukin-12, interleukin-6, tumor necrosis factor-α and interferon-γ and executed positive anti-tumor effects. In addition, under the protection of tumor-homologous cytomembrane, the "nanoconverter" exhibited excellent delivery efficiency (23.22%), and subsequently, accumulated special structural "nanoconverter" could break down into smaller nanoparticles for deep penetration into the tumor tissue under a NIR laser. Ultimately, chemo/thermal therapy-assisted immunotherapy completely eliminated the tumors of tumor-bearing mice, and a potent memory response relying on effector memory T cells still persisted to protect against tumor relapse after the end of treatment. The "nanoconverter" serves as a promising nanodrug delivery system for the conversion of immunosuppression and enhanced chemo/thermal therapy. Therefore, the highly cumulative "nanoconverter" has great potential for promoting the effect and clinical application of immunotherapy.

• Authors: Cong Cong, Bian Jiaxin, Xiaokang Liu, Xinyue Zhang, Yihan Fu, Zhuo Li, Zichuang Xu, Shipan Wei, Desong Wang, Dawei Gao
• Journal: Journal of materials chemistry. B (J Mater Chem B) Vol. 9 Issue 9 Pg. 2323-2333 (03 11 2021) ISSN: 2050-7518 [Electronic] England
• PMID: 33621309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• Indoles
• Interleukin-6
• Polymers
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• polydopamine
• Interleukin-12
• Interferon-gamma
• Paclitaxel

Topics

• Animals
• Cell Transformation, Neoplastic
• Ceramides (chemistry)
• Humans
• Immunotherapy (methods)
• Indoles (chemistry)
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Interleukin-6 (metabolism)
• Macrophages (cytology, metabolism)
• Mice
• Nanostructures (chemistry)
• Paclitaxel (chemistry, metabolism, pharmacology)
• Phenotype
• Polymers (chemistry)
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)