Nanocarriers with multi-locked DNA valves targeting intracellular tumor-related mRNAs for controlled drug release.

The fabrication of well-behaved drug delivery systems that can transport drugs to specifically treat cancer cells rather than normal cells is still a tremendous challenge. A novel drug delivery system with two types of tumor-related mRNAs as "keys" to open the multiple valves of the nanocarrier to control drug release was developed. Hollow mesoporous silica nanoparticles were employed as the nanocarrier and dual DNAs targeting two intracellular mRNAs were employed as "multi-locks" to lock up the nanocarrier. When the nanocarrier enters the cancer cells, the overexpressed endogenous mRNA keys hybridize with the DNA multi-locks to open the valves and release the drug. Each single mRNA could not trigger the opening of the locks to release the cargo. Therefore, the nanocarrier can be applied for specific chemotherapy against cancer cells with minor side effects to normal cells. The current strategy could provide an important avenue towards advancing the practical applications of drug delivery systems used for cancer therapy.