关键词: Bacterial outer membrane vesicle Biomimetic nanoparticles Breast cancer bone metastasis Hybrid membrane Sonodynamic therapy

Mesh : Female Animals Breast Neoplasms / therapy pathology Mice Bone Neoplasms / secondary therapy Cell Line, Tumor Mice, Inbred BALB C Bacterial Outer Membrane Ultrasonic Therapy / methods Polylactic Acid-Polyglycolic Acid Copolymer / chemistry Humans Nanoparticles / chemistry therapeutic use RAW 264.7 Cells Cell Membrane Multifunctional Nanoparticles / chemistry

来  源:   DOI:10.1186/s12951-024-02619-w   PDF(Pubmed)

Abstract:
Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.
摘要:
乳腺癌骨转移是一种晚期疾病,通常采用放疗和化疗治疗,这导致严重的副作用和有限的有效性。为了改善这一点,声动力疗法可能是未来更安全有效的方法。细菌外膜囊泡(OMV)具有优异的免疫调节特性,包括调节巨噬细胞极化,促进DC细胞成熟,增强抗肿瘤作用。将OMV与声动力疗法结合可以产生协同抗肿瘤作用。因此,我们构建了多功能纳米颗粒用于治疗乳腺癌骨转移。我们将乳腺癌细胞膜和细菌外膜囊泡融合形成杂化膜(HM),然后将负载IR780的PLGA与HM封装在一起以产生纳米颗粒,IR780@PLGA@HM,具有肿瘤靶向性,免疫调节,和声动力学能力。实验表明,IR780@PLGA@HM纳米粒子具有良好的生物相容性,有效靶向4T1肿瘤,促进巨噬细胞I型极化和DC细胞活化,抗肿瘤炎症因子表达增强,并表现出在体外和体内有效杀死肿瘤的能力,对乳腺癌骨转移有很好的治疗效果。因此,我们构建的纳米颗粒为有效治疗乳腺癌骨转移提供了新的策略。
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