Vitamin D3/phospholipid complex decorated caseinate nanomicelles for targeted delivery of synergistic combination therapy in breast cancer
Vitamin D3/phospholipid complex decorated caseinate nanomicelles for targeted delivery of synergistic combination therapy in breast cancer
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DOI：
10.1016/j.ijpharm.2021.120965
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发表时间：
2021-08-09
影响因子：
5.8
通讯作者：
Sabra, Sally
中科院分区：
文献类型：
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作者：
Agwa, Mona M.;Abu-Serie, Marwa M.;Sabra, Sally
细胞毒药物的靶向给药在肿瘤治疗中显示出巨大的潜力。维生素D3（Vit. D3）-包被的胶束被制造成包封细胞毒性药物;依托泊苷（ETP）。首先利用酪蛋白酸钠胶束将维生素D3和ETP包封在其疏水核心内，然后用维生素D3/磷脂复合物的包膜进一步修饰载药胶束，以通过利用乳腺癌细胞外表面上过表达的维生素D3受体（VDR）来增强所制造的胶束的主动靶向效力。体外细胞毒性研究表明，与游离维生素D3 + ETP相比，所制备的胶束对MDA MB-231和MCF-7人乳腺癌细胞系表现出改善的抗癌作用，而对正常人肺成纤维细胞（Wi-38）无任何显著毒性。在埃利希腹水肿瘤动物模型中的体内生物分布和功效研究揭示，由于维生素D3的主动靶向潜力，所制造的胶束表现出在肿瘤组织中的改善的积累，而没有任何显著的毒性。更重要的是，除了miR-21和miR-192的肿瘤表达水平下降之外，制造的胶束还导致增强的肿瘤凋亡、减少的血管生成、侵袭和自噬。因此，维生素D3/ETP胶束可以作为一个有利的主动靶向抗癌传递系统，具有上级效果超过自由组合。
Targeted delivery of cytotoxic drugs has shown great potential in cancer therapy. In this light, vitamin D3 (vit. D3)-coated micelles were fabricated to encapsulate the cytotoxic drug; etoposide (ETP). Sodium caseinate micelles were first utilized to encapsulate vit.D3 and ETP within their hydrophobic core, then drug-loaded micelles were further decorated with an envelope of vit.D3/ phospholipid complex to enhance the active targeting potency of fabricated micelles via exploiting vit.D3 receptors (VDRs) overexpressed on the outer surface of breast cancer cells. In vitro cytotoxicity studies showed that fabricated micelles exhibited improved anticancer effect on MDA MB-231 and MCF-7 human breast cancer cell lines in comparison to free vit.D3 + ETP without any significant toxicity on normal human lung fibroblast (Wi-38) cells. In vivo biodistribution and efficacy studies in Ehrlich ascites tumor animal model revealed that fabricated micelles manifested improved accumulation in tumor tissue due to active targeting potential of vit.D3 without any remarkable toxicity. More importantly, fabricated micelles resulted in enhanced tumor apoptosis, reduced angiogenesis, invasion and autophagy, besides a decline in the tumor expression levels of both miR-21 and miR-192. Therefore, vit.D3/ETP micelles could serve as a favorable actively targeted anticancer delivery system having a superior effect over the free combination.