Drug-mediation formation of nanohybrids for sequential therapeutic delivery in cancer cells.

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.