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载紫杉醇和盐霉素的脂质纳米胶囊联合用于根除乳腺癌和肿瘤干细胞。

Lipid nanocapsules co-encapsulating paclitaxel and salinomycin for eradicating breast cancer and cancer stem cells.

机构信息

Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India.

Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India.

出版信息

Colloids Surf B Biointerfaces. 2021 Aug;204:111775. doi: 10.1016/j.colsurfb.2021.111775. Epub 2021 Apr 19.

Abstract

Cancer stem cells (CSCs) comprise a diminutive population of the tumor but pose major obstacles in cancer treatment, often their presence being correlated with poor prognosis, therapeutic resistance and relapse. Nanocarriers of combined drugs regimes demonstrate improved pharmacokinetics and decreased systemic toxicity by targeting the bulk tumor cells along with CSCs, holding the key to future successful chemotherapy. Herein, we developed lipid nanocapsules (LNCs) with co-encapsulated paclitaxel (PTX) and salinomycin (SAL) to eliminate breast cancer cells (MCF-7; non-bCSCs) and cancer stem cells (bCSCs) respectively. LNCs loaded with either PTX or SAL alone or in combination were fabricated by the phase inversion temperature (PIT) method. Physicochemical properties such as nano-size (90 ± 5 nm) and spherical morphology of LNCs were confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM) respectively. More than 98 % encapsulation efficiency of drug, alone or in combination, and their controlled drug release was obtained. Drug loaded LNCs were efficiently internalized and exhibited cytotoxicity in non-bCSCs and bCSCs, with dual drug loaded LNCs offering superior cytotoxicity and anti-bCSCs property. Drug loaded nanocapsules induced apoptosis in bCSCs, potentiated with the co-delivery of paclitaxel and salinomycin. Synergistic cytotoxic effect on both cells, non-bCSCs and bCSCs and effective reduction of the tumor mammospheres growth by co-encapsulated paclitaxel and salinomycin suggest LNCs to be promising for treatment of breast cancer.

摘要

癌症干细胞(CSCs)构成了肿瘤的一小部分,但在癌症治疗中构成了主要障碍,它们的存在通常与预后不良、治疗耐药和复发相关。联合药物治疗的纳米载体通过靶向大量肿瘤细胞和 CSCs,改善了药代动力学和降低了全身毒性,为未来成功的化疗提供了关键。在此,我们开发了共包载紫杉醇(PTX)和萨利霉素(SAL)的脂质纳米胶囊(LNCs),分别用于消除乳腺癌细胞(MCF-7;非 bCSCs)和癌症干细胞(bCSCs)。通过相转变温度(PIT)法制备了单独负载 PTX 或 SAL 或联合负载的 LNCs。通过动态光散射(DLS)和扫描电子显微镜(SEM)分别证实了纳米胶囊的物理化学性质,如纳米尺寸(90±5nm)和球形形态。单独或联合负载药物的载药效率超过 98%,并实现了药物的控制释放。负载药物的纳米胶囊在非 bCSCs 和 bCSCs 中被有效内化,并表现出细胞毒性,双载药纳米胶囊具有更好的细胞毒性和抗 bCSCs 特性。负载药物的纳米胶囊在 bCSCs 中诱导细胞凋亡,与紫杉醇和萨利霉素的共递送协同增强。对两种细胞(非 bCSCs 和 bCSCs)的协同细胞毒性作用以及紫杉醇和萨利霉素共包封有效降低肿瘤类球体生长,表明 LNCs 有望用于治疗乳腺癌。

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