Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma

• Published in: Journal of nanobiotechnology 2024-04, Vol.22 (1), p.168-168, Article 168
• Main Authors: Yang, Lin, Li, Hongjiao, Luo, Aihua, Zhang, Yao, Chen, Hong, Zhu, Li, Yang, Deqin
• Format: Article
• Language: English
• Subjects: Acids; Animals; Anticancer properties; Antitumor activity; Biocompatibility; Breast cancer; Cancer; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Cell membranes; Cells; Chemical properties; Chemotherapy; Core-shell structure; Cytotoxicity; Doxorubicin; Doxorubicin - pharmacology; Drug delivery systems; Drug therapy; Drugs; Ethylenediaminetetraacetic acid; Flow cytometry; Fluorescence; Head and Neck Neoplasms; Health aspects; Hydrogen-Ion Concentration; Immune clearance; Immune evasion; Immune system; Immunosuppressive agents; Macrophage membrane; Macrophages; Maleic anhydride; Membranes; Metastasis; Mice; Monoclonal antibodies; Mouth cancer; Mouth Neoplasms - drug therapy; Nanoparticles; Nanotechnology; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Penicillin; pH effects; pH-sensitive; Pharmaceutical research; Pharmacokinetics; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Target delivery; Tissue Distribution; Toxicity; Tumor cells; Tumor Microenvironment; Tumor suppression; Tumors; Vehicles; Vinyl ethers
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02433-4

Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.