Development of surface engineered polymeric nanocarriers to mediate the extended delivery of transferrin-methotrexate for treating brain cancer.Treating brain cancers is difficult because of the blood-brain barrier (BBB), which protects the body’s most vital organ. This security system of blood vessels lined with tightly packed endothelial cells lets in essential nutrients, but keeps out foreign substances so effectively that the delivery of life-saving drugs is also blocked. But in a step towards overcoming the BBB, researchers from India and the USA have engineered the surface of nanosized polymeric drug carriers to bind onto cancer cells [Jain et al., Acta Biomaterialia (2015), http://dx.doi.org/10.1016/j.actbio.2015.06.027].
While the BBB is very good at blocking large molecules from entering, much smaller and/or fat-soluble molecules are able to slip past the endothelial cell barrier. So the researchers, led by Vandana Soni at Dr Hari Singh Gour University in India and Thomas J. Webster at Northeastern University, designed a nanocarrier system based on poly (D,L-lactide-co-glycolide) (PGLA) nanoparticles coated with a water-soluble surfactant, polysorbate 80, and loaded with a protein (transferrin, Tf) that binds onto cancer cells and an anticancer drug (methotrexate, Mtx). The other authors of the study are Neeraj K. Garg, Rajeev K. Tyagi, Atul Jain, Ashay Jain, Bhupinder Singh, and O.P. Katare.
“To be an efficient delivery vehicle, polymeric nanocarriers must encompass multifunctional properties like biocompatibility, bio-distribution, non-toxicity, and be capable of overcoming biological barriers,” explains Tyagi. “[Our] nanoparticles are nanometric in range (~200 nm) and lipophilic in nature, which helps them cross the BBB.”
The protective polysorbate 80 coating helps the nanoparticles cross the BBB, while the addition of transferrin enables them to targets tumor cells and penetrate the cell membrane. Once in the brain, the combination also regulates the release of methotrexate, leading to long-lasting drug delivery. Importantly, the better targeting of cancer cells reduces the dose of methotrexate received by other healthy cells.
“Selective and targeted delivery of cytotoxic drugs towards malignant tumors might overcome loopholes with the existing therapeutic system when talking about brain cancer,” says Tyagi. “Polysorbate-80 coated polymeric nanoparticles conjugated with Tf-Mtx not only provide specific targeting across the BBB, but also suppress possible adverse effects in peripheral normal tissues/cells.”
In tests with rats, the surface-engineered nanoparticles led to higher cellular uptake of the methotrexate and greater cytotoxicity of tumor cells compared with simply administering the drug alone.
“This therapeutic approach needs to be further explored,” Tyagi told Materials Today, “but we believe our delivery system will open new avenues and come up with innovations in brain cancer and its treatment.”