乳腺癌是一种异质性疾病，全球每年约有 100 万新发病例。化疗仍是主要治疗选择，但抗肿瘤疗效有待提高。本文以油酸和mPEG2k-PCL2k为药物载体，研制了两种多功能纳米颗粒。 Squamocin (Squ) 被用作化疗剂。将Resiquimod（R848）或人参皂苷Rh2共封装在纳米颗粒中，重塑免疫抑制的肿瘤微环境，共负载IR780作为光敏剂，实现光热治疗。所得Squ-R848-IR780纳米颗粒和Squ-Rh2-IR780纳米颗粒均匀球形，平均直径分别约为（162.200±2.800）nm和（157.300±1.1590）nm，具有良好的包封率（每种药物均在85%以上），在各种生理介质中稳定性优异，光热转换效率高（24.10%）和 22.58%）。静脉注射后，这两种纳米粒子在肿瘤中迅速积累，并在808 nm激光照射下有效地将肿瘤局部温度提高到45°C以上。在0.1 mg/kg的低剂量下，Squ纳米粒子单独治疗的肿瘤抑制率为55.28%，肺转移抑制率为59.47%，平均生存时间为38天，均高于PTX注射液（8 mg/kg）（43.64%、25 天和 37.25%），表明 Squ 是一种强效且有效的抗肿瘤剂。多功能纳米粒子Squ-Rh2-IR780纳米粒子和Squ-R848-IR780纳米粒子均表现出更好的治疗效果，肿瘤抑制率分别为90.02%和97.28%，肺转移抑制率分别为95.42%和98.09%，平均生存时间为分别为46天和52天。共同负载squamocin、R848和IR 780的多功能纳米粒子取得了非凡的治疗效果和优异的抗转移活性，因此在未来乳腺肿瘤和其他肿瘤的治疗中具有广阔的前景。© 2024 Wang et al.

Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved.Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy.The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively.The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.© 2024 Wang et al.