Cancer is often referred to as “smart,” and this term often refers to the ability of these cells to proliferate without purpose or restraint. The ability of cancer cells to develop multidrug resistance (MDR), a major problem that patients can face, making treatment against this disease even more elusive.
In an effort to combat both cancer cell proliferation and MDR, a recent study conducted by researchers from the National Health Research Institutes of Taiwan and the National Science Council of Taiwan have developed a nanosystem capable of addressing both challenges in the field of cancer therapy.
Drug Resistance and Cancer
Patients with several forms of blood cancer and solid tumors in the breast, ovaries, lungs and lower gastrointestinal tract can become untreatable as a result of multidrug resistance (MDR). In MDR, the cancer cells of these patients become resistant to commonly used therapeutic drugs as a result of an overexpression of ATP-binding cassette (ABC) transporters that effectively push out drug molecules following administration. P-glycoprotein and what is termed as the multidrug resistance-associated protein (MRP) are two of the most studied pumps present in cancer cells that are capable of rejecting chemotherapeutic drugs. By avoiding the toxic effects of these drugs, cancer cells are able to continue to proliferate and metastasize to other organs of the body.
Unfortunately, some of the most commonly used cancer therapeutic drugs such as colchicine, vinblastine, doxorubicin, etoposide, paclitaxel, certain vinca alkaloids and other small molecules have shown resistance in various cancer cells. Current research efforts in the field of anticancer drug discovery have looked towards the administration of combinatorial technology to be administered with cancer to effectively prevent cancer cells from physically removing therapeutic drugs when administered together.
While blocking the action of pumps like MRP and P-glycoprotein has shown some efficacy, transcription factors, such as c-Jun, which plays a role in cell, proliferation and MDR, can still potentiate metastasis. Therefore, there remains a need to develop cancer therapies that work against drug resistance and simultaneously prevent further metastasis.
The Efficacy of Administering Doxorubicin Mesoporous Silica Nanoparticles (MSNs)
Mesoporous silica nanoparticles (MSNs) are well-documented drug delivery vehicles that allow for a high drug loading capacity with minimal side effects upon administration. The tunable size properties, thermal stability, photostability and ease of functionalization to different applications make MSNs one of the most promising options for therapeutic delivery systems. In the recent study published in Nano Futures, the group of scientists led by Leu-Wei Lo covalently conjugated MSNs with doxorubicin and tested the ability of these nanosystems to be taken up by cancer cells in vitro.
The PC-3 cell line of metastatic human prostate carcinoma cells were treated with 100 μg/ml of either Dox-MSNs that were conjugated with DNAzyme, (Dox-MSN-Dz), Dox-MSNs or control MSNs for 24 hours to study the ability of these cells to survive following treatment. The researchers found the Dox-MSN-Dz reduced cell survival rates by over 80%, whereas the Dox-MSNs alone still reduced cell survival rates by 60%.
The results of this study confirm the therapeutic potential of the developed multifunctional nanosystem, which incorporates doxorubicin, a widely used chemotherapeutic drug, MSNs and DNAzyme. Not only did this nanosystem improve the cytotoxicity of doxorubicin to a resistance cancer cell line, but it also successfully reduced migration of cancer cells by inhibiting c-Jun.
While further in vivo studies need to be conducted to fully evaluate the ability of Dox-MSN-Dz to prevent metastasis and invade highly resistance cancer cells, the results of this study are promising. Future research initiatives that incorporate different chemotherapeutic drugs into a similar nanosystem design could also show similar bifunctional properties as presented here.
- “A co-delivery nanosystem of chemotherapeutics and DNAzyme overcomes cancer drug resistance and metastasis” S. Sun, C. Liu, et al. Nano Futures. (2017). DOI: 10.1088/2399-1984/aa996f.