Most chemotherapy treatments involve a combination of therapeutics to prevent drug resistance in cancer patients. However, cancer cells can adapt and become resistant to one or more of the drugs employed – something that ultimately leads to the treatment failing.

A team led by Andre Nel, Jeffrey Zink and Huan Meng at UCLA has now shown that mesoporous silica nanoparticles (MSNPs) can overcome resistance to the cancer drug doxorubicin in a human breast cancer xenograft. The nanocarriers can deliver the cancer drug and siRNA, which targets P-glycoproteins (responsible for drug resistance in a tumour cell), and so effectively inhibit tumour growth (ACS Nano doi: 10.1021/nn3044066).

The MSNP platform developed by the UCLA team, which is described in detail in ACS Nano, was designed to target a tumour site following intravenous injection. The particle surface is functionalized with a phosphonate group that allows the cancer drug to electrostatically bind to the porous interior of the nanoparticles, from where the drug can be released inside cancer cells by a specific cell organelle. The phosphonate groups can also be coated with the cationic co-polymer PEI-PEG, which allows the nanoparticles to carry and then deliver a variety of siRNA molecules that target different multidrug resistant pathways in the cancer cells.

Slowing down tumour growth

"Our dual nano-delivery system results in more potent inhibition of tumour growth compared with the free drug or the carrier loaded with drug or siRNA alone," Meng said. "And, while our experiments provide proof-of-principle for the concept of dual drug and siRNA delivery in vivo, we believe that we can further improve this system," he told our sister site nanotechweb.org. "For one, we can design the nanoparticles to also enter blood vessels in which the tumour acts as a barrier to drug entry."

The researchers say that their MSNP platform is biocompatible. Encapsulating toxic cancer drugs in the MSNP also reduces their toxicity.

"Our results are encouraging in that we can now think about moving the platform into clinical trials as well as introducing additional design features for more efficient and safer drug and siRNA dual delivery at tumour sites," added Nel. "The technique could also potentially be used to develop treatments for individual patients by selecting specific drug/siRNA combinations."