16 January 2019
Nanocarriers are a useful means for transporting exact doses of drugs to specific points in the body, for example to target tumours in cancer therapy. Now, researchers in China have developed a novel nanocarrier that can transport precise ratios of two drugs to treat nonsmall-cell lung cancer.
Non-small-cell lung cancer is the most common form of lung cancer, representing 85 per cent of cases, but it is relatively insensitive to chemotherapy. Surgery is often required, either preceded or followed by treatment with a combination of two anticancer drugs, gemcitabine and paclitaxel. A key goal in reﬁning the delivery of these two drugs to tumour sites is ensuring that precise ratios of the drugs are released to optimise their combined eﬀect.
The new nanocarrier, developed by a team led by Jingtian Han at Binzhou Medical University and Zimei Wu at Yantai University, diﬀers from more traditional nanoparticle designs because it contains both solid and liquid lipids. These ‘nanostructured lipid carriers’ (NLCs) have improved loading capacity and stability, and can carry two drugs that have diﬀering physical and chemical characteristics.
Gemcitabine and paclitaxel target diﬀerent elements of the cancer cell cycle, interfering with DNA synthesis and microtubule growth respectively. Varied ratios of the drugs used in combination have diﬀerent eﬀects, and the aim is to deliver the optimal amount of each drug to a tumour.
Han and Wu trialled the effects of various ratios of the two drugs by carefully placing different quantities of each on a macromolecule, which was joined to the inside of the NLC by breakable linker molecules. Upon reaching its target, the NLC opens as the linker molecules break, and the drugs are released. By creating multiple versions of their NLC, the researchers were able to select an optimised NLC that was more cytotoxic against non-small-cell lung cancer cells than any previous treatments.
Han and Wu included a glucose receptor-targeting molecule, N-acetyl-D-glucosamine, (NAG) within their NLC design. Tumours feed oﬀ glucose, and therefore express high levels of glucose transporters on their surfaces. The NAG-NLC prepared by the team used this mechanism to target non-small-cell lung cancer cells with high accuracy.
As the researchers state in their paper published in the International Journal of Nanomedicine (2017): “[The NAGNLCs] we designed can be beneficial to tumour therapy. Future research should be encouraged to investigate a dose-dependent response and optimal doses with maximal anticancer efficacy, but fewer side effects.”