Controllably Switched Drug Release from Successively Dual-Targeted Nanoreservoirs

The development of a nanocarrier with a capacity of releasing therapeutic agent "on demand" is of great importance for enhancing drug efficacy and reducing its side effect. Here, a multifunctional mesoporous silica nanoparticle is presented for cancer therapy. This nanoparticle can not only successively target tumor tissue and tumor cells but also has a function of controllably switching the drug release. Low molecular weight poly(ethyleneimine) segments, which are decorated on the surface of magnetic mesoporous silica nanoparticle with disulfide bonds, are chemically cross-linked, leading to the mesopores being "closed" in blood circulation but being "open" via taking off the coating in cytoplasm. As a result, the encapsulated drug can be kept in nanoparticles in the normal conditions, while be rapidly released in a reduction condition. In vivo antitumor activity demonstrates that this nanoparticle has the highest safety to body and the best therapeutic efficacy against tumors. Therefore, this work presents a good example of rational design of nanocarriers for highly effective cancer therapy.