Schematic showing the injection of paclitaxel-carrying chitosan-PEG fibers into a blood vessel, where they dissemble into tiny drug-carrying nanoparticles.A drug-carrying nanofiber that splits into tiny nanoparticles once inside the body could offer a new strategy for anticancer therapy, according to researchers at the University of Washington [Mu et al., Materials Today (2020), https://doi.org/10.1016/j.mattod.2020.03.005].
Nanoparticles can be loaded with therapeutic agents and injected into the body to deliver drugs safely and with greater efficacy, which is particularly desirable for cancer treatment, where side effects can be severe. An effective nanocarrier needs to be small – ideally less than 100 nm in diameter – even when loaded with its drug cargo to evade the immune system and must remain stable in the blood to allow it to circulate long enough to reach its target. Not only that, but the carrier must also be biocompatible.
Miqin Zhang and her team has come up with a clever to solution by creating a stable nanofiber with good drug loading capacity that splits into much smaller nanoparticles once inside the body. The nanofiber is synthesized from chitosan, a widely used biocompatible and biodegradable pharmaceutical ingredient, and polyethylene glycol (PEG) via a self-assembly process. In fiber form, the material is very stable and can be stored for months in the lab.
“We have introduced an innovative nanotherapeutic strategy by forming stable hydrophobic cancer drug (paclitaxel) conjugated nanofibers in solution. After entering the body, the drug-loaded nanofibers encounter serum proteins and rapidly fragment into ultrafine nanoparticles to deliver the drug,” explains first author of the study, Qingxin Mu. “The nanofibers fragment into near-spherical nanoparticles within a minute,” he adds.
Despite dissembling into smaller particles just 20 nm in diameter, the covalent bonds binding the drug to the chitosan-PEG fiber do not break in serum and the drug loading capacity is maintained.
“The nanoparticles travel through various biological barriers and release drug at the tumor site. Eventually, drug is metabolized by liver enzymes and cleared, with excipients degraded from the body,” says Mu.
The team demonstrates this using paclitaxel, a clinically approved anticancer drug used to treat a range of solid tumors. In mouse models of aggressive drug-resistant breast cancer and melanoma, the new delivery system shows improved circulation times in the blood, low systemic toxicity, better localization of nanoparticles at the tumor, and enhanced inhibition of tumor growth and metastasis. The nanoparticles outperform the clinically used form of the drug, say the researchers, in terms of minimizing toxicity and the effectiveness of the treatment.
“The good stability, small nanoparticles size, and good drug loading render the approach suitable for hydrophobic drug delivery,” says Mu.
The team now plans to explore whether the approach could work with other water-insoluble drugs and in different cancer models.