背景:口腔癌是头颈部最常见的恶性肿瘤,90%的病例是口腔鳞状细胞癌(OSCC)。化疗是OSCC综合治疗的重要组成部分。然而,化疗药物的临床治疗效果,如阿霉素(DOX),由于缺乏肿瘤靶向和免疫系统的快速清除而受到限制。因此,基于巨噬细胞的肿瘤靶向和免疫逃避能力,巨噬细胞膜包裹的聚(甲基乙烯基醚alt马来酸酐)-苯基硼酸-阿霉素纳米颗粒(MM@PMVEMA-PBA-DOXNPs),简短地说是MM@DOXNPs,旨在针对OSCC。PBA和DOX之间的硼酸酯键响应肿瘤微环境中的低pH值,有选择地释放装载的DOX。
结果:结果表明,MM@DOXNPs表现出均匀的粒径和典型的核壳结构。当pH从7.4降低到5.5时,药物释放从14%增加到21%。体外靶向能力,免疫逃避能力,在HN6和SCC15细胞系中验证了MM@DOXNPs的细胞毒性。与免费DOX相比,流式细胞术和荧光图像显示肿瘤细胞对MM@DOXNPs的摄取较高,而巨噬细胞对MM@DOXNPs的摄取较低。细胞毒性和活/死染色实验表明,MM@DOXNP比游离DOX表现出更强的体外抗肿瘤作用。在体内进一步证实了靶向和治疗效果。基于纳米粒子的体内生物分布,MM@DOXNPs在肿瘤部位的积累增加。药代动力学结果表明,MM@DOXNP的半衰期更长,为9.26h,而游离DOX的半衰期为1.94h。此外,MM@DOXNPs在HN6荷瘤小鼠中表现出较强的抑瘤作用和良好的生物相容性。
结论:因此,MM@DOXNPs是一种安全有效的OSCC治疗平台。
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.