The First Affiliated Hospital of Hainan Medical University, Department of Ultrasound, Haikou, Hainan, China.
Biomater Sci. 2024 Sep 25;12(19):4980-4992. doi: 10.1039/d4bm00772g.
The treatment of unresectable locally advanced triple-negative breast cancer (TNBC) and TNBC with metastasis is challenging. Many anticancer drugs, such as doxorubicin, still hinder positive therapeutic outcomes due to severe side effects. Photodynamic therapy (PDT) has an anticancer effect, and combining PDT with chemotherapy may improve breast cancer therapy. The use of cargo-loaded biomimetic PEGylated liposomes for cancer therapy may enhance efficacy and reduce side effects. In this study, liposomes were formulated to accommodate doxorubicin (Dox) and IR780. Breast cancer cells (4T1 cells) and macrophage cell membranes were isolated and camouflaged onto the PEGylated liposomes, creating a new biomimetic platform called Dox-IR780@Lip@Ms. The Dox-IR780@Lip@Ms platform was characterized and tested and . The results showed that the Dox-IR780@Lip@Ms had an ovoid shape with a double lamina structure, monodispersity, and uniform distribution. The size was 132.37 ± 1.22 nm, the PDI was 0.044 ± 0.067, and the zeta potential was -9.67 ± 1.08 mV. The encapsulation efficiency of Dox and IR780 in Dox-IR780@Lip@Ms was 89.36% ± 3.07% and 92.34% ± 0.66%, respectively. The release rate of Dox from Dox-IR780@Lip@Ms was good after laser irradiation. At pH 7.4, the release rate of Dox was 23.85% ± 0.62% at 3 h without laser irradiation and 36.62% ± 1.32% at 3.5 h with laser irradiation. At pH 6.5, the release rate of Dox was 32.54% ± 0.32% at 3 h without laser irradiation and 62.79% ± 2.15% at 3.5 h with laser irradiation. The cytotoxicity of IR780@Lip@Ms was lower than that of Dox-IR780@Lip@Ms. The cell uptake and generation of reactive oxygen species of Dox-IR780@Lip@Ms were significant. Dox-IR780@Lip@Ms exhibited immune escaping ability , homotypic targeting ability to cancer cells, high capability to kill cancer cells after laser irradiation, minimal cardiotoxicity, increased accumulation of Dox and IR780 in the tumor, and an increased anticancer effect in a tumor-bearing animal model. In conclusion, hybrid cell membranes of breast cancer and macrophages camouflaging PEGylated liposomes loaded with Dox and IR780 can significantly improve breast cancer therapy after laser irradiation in murine models.
无法切除的局部晚期三阴性乳腺癌（TNBC）和转移性 TNBC 的治疗具有挑战性。许多抗癌药物，如阿霉素，由于严重的副作用仍然阻碍了积极的治疗效果。光动力疗法（PDT）具有抗癌作用，将 PDT 与化疗相结合可能改善乳腺癌的治疗效果。使用载药仿生聚乙二醇化脂质体进行癌症治疗可能会提高疗效并降低副作用。在这项研究中，制备了脂质体来容纳阿霉素（Dox）和 IR780。分离并伪装乳腺癌细胞（4T1 细胞）和巨噬细胞膜到聚乙二醇化脂质体上，创建了一个名为 Dox-IR780@Lip@Ms 的新仿生平台。对 Dox-IR780@Lip@Ms 平台进行了表征和测试。结果表明，Dox-IR780@Lip@Ms 呈卵形，具有双层结构，单分散性和均匀分布。大小为 132.37 ± 1.22nm，PDI 为 0.044 ± 0.067，zeta 电位为-9.67 ± 1.08mV。Dox-IR780@Lip@Ms 中 Dox 和 IR780 的包封效率分别为 89.36%±3.07%和 92.34%±0.66%。Dox-IR780@Lip@Ms 在激光照射后释放 Dox 的效果良好。在 pH7.4 下，无激光照射 3 小时时 Dox 的释放率为 23.85%±0.62%，激光照射 3.5 小时时为 36.62%±1.32%。在 pH6.5 下，无激光照射 3 小时时 Dox 的释放率为 32.54%±0.32%，激光照射 3.5 小时时为 62.79%±2.15%。IR780@Lip@Ms 的细胞毒性低于 Dox-IR780@Lip@Ms。Dox-IR780@Lip@Ms 的细胞摄取和活性氧的产生显著。Dox-IR780@Lip@Ms 具有免疫逃逸能力、对癌细胞的同型靶向能力、激光照射后杀死癌细胞的能力高、心脏毒性最小、肿瘤内 Dox 和 IR780 的蓄积增加以及荷瘤动物模型中的抗癌效果增加。总之，负载 Dox 和 IR780 的仿生乳腺癌和巨噬细胞膜混合的聚乙二醇化脂质体可以显著提高小鼠模型中激光照射后的乳腺癌治疗效果。
