The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
College of Materials Science and Engineering, Zhejiang University of Technology, 310014, China.
Colloids Surf B Biointerfaces. 2018 Mar 1;163:284-290. doi: 10.1016/j.colsurfb.2017.12.046. Epub 2017 Dec 29.
In order to overcome the multidrug resistance (MDR) of tumor cells, it is very important to develop nanocarriers which can effectively load drugs while releasing them in a sequential way. Herein, nanohybrids with such properties have been fabricated by a first loading of one anticancer drug onto a silicate nanodisk (Laponite (LP), 25 nm in diameter and 0.92 nm in thickness) and a subsequent assembly with a pH sensitive poly(N-vinylpyrrolidone) (PVP) as a protective layer, followed by a loading of with another anticancer drug. The resulting nanohybrids (LDPM) present a high drug encapsulation efficiency and long-term colloidal stability. However, if the two drugs are loaded onto LP before PVP decoration, the formed particles tend to form microsized aggregates with poor colloidal stability. In vitro release study indicates that LDPM can deliver the anticancer drugs in a sequential way, which can be further accelerated under acidic microenvironments mimicking both solid tumor and endo-lysosomal compartments, exerting synergistic anticancer cytotoxicity. The drug-mediated formation of nanocarriers may enlighten a design of novel nanoplatform for co-delivery of therapeutic agents, beyond anticancer drugs, in a combinative way for drug delivery applications.
为了克服肿瘤细胞的多药耐药性（MDR），开发能够有效负载药物并以顺序方式释放药物的纳米载体非常重要。在此，通过将一种抗癌药物首先负载到硅酸盐纳米盘中（Laponite（LP），直径为 25nm，厚度为 0.92nm），然后与 pH 敏感的聚（N-乙烯基吡咯烷酮）（PVP）作为保护层进行组装，随后再负载另一种抗癌药物，制备了具有这种特性的纳米杂化物（LDPM）。所得纳米杂化物（LDPM）具有高的药物包封效率和长期胶体稳定性。然而，如果在 PVP 修饰之前将两种药物负载到 LP 上，则形成的颗粒容易形成胶体稳定性差的微尺寸聚集体。体外释放研究表明，LDPM 可以以顺序方式释放抗癌药物，在模拟实体瘤和内溶酶体区室的酸性微环境下可以进一步加速释放，从而发挥协同抗癌细胞毒性作用。药物介导的纳米载体的形成可能为联合药物递送应用中除抗癌药物以外的治疗剂的联合共递药新型纳米平台的设计提供启示。
