Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Nanomedicine. 2018 Nov;14(8):2678-2688. doi: 10.1016/j.nano.2018.06.012. Epub 2018 Jul 9.
Treatment of metastatic cancer continues to be a huge challenge worldwide. Notably, drug nanocrystals (Ns) in nanosuspensions clearly belong to a type of nanoparticle. Therefore, a question arose as to whether these drug particles can also be applied as carriers for drug delivery. Here, we design a novel paclitaxel (PTX) nanocrystal stabilized with complexes of matrix metalloproteinase (MMP)-sensitive β-casein/marimastat (MATT) for co-delivering MATT and PTX and combined therapy of metastatic breast cancer. The prepared Ns (200 nm) with a drug-loading of >50% were potent in treatment of metastatic cancer, which markedly inhibited MMP expression and activity and greatly blocked the lung metastasis and angiogenesis. In conclusion, employing protein-drug complexes as stabilizers, Ns with dual payloads are developed and are a promising strategy for co-delivery. Furthermore, the developed Ns can target the tumor microenvironment and cancer cells and, as a result, enable efficient treatment for breast metastatic cancer.
转移性癌症的治疗仍然是全球范围内的一个巨大挑战。值得注意的是，纳米悬浮液中的药物纳米晶体（Ns）显然属于纳米颗粒的一种。因此，人们提出了一个问题，即这些药物颗粒是否也可以用作药物递送的载体。在这里，我们设计了一种新型紫杉醇（PTX）纳米晶体，该晶体由基质金属蛋白酶（MMP）敏感的β-酪蛋白/马立司他（MATT）复合物稳定，用于共递送 MATT 和 PTX 以及联合治疗转移性乳腺癌。所制备的载药量超过 50%的纳米晶体（200nm）在治疗转移性癌症方面非常有效，它显著抑制 MMP 的表达和活性，并大大阻断了肺转移和血管生成。总之，采用蛋白质-药物复合物作为稳定剂，开发了具有双重载药能力的纳米晶体，这是一种很有前途的共递药策略。此外，所开发的纳米晶体可以靶向肿瘤微环境和癌细胞，从而实现对乳腺癌转移的有效治疗。
