A German research team have provided proof-of-concept evidence for site-selective release of medicines by nanocarriers at lung tumor sites in mouse and human tissues. The study, published recently in the journal ACS Nano, reports how the approach promoted notable increases in the efficacy of current cancer medicines in lung tumor tissue.
The scientists modified the nanocarriers to release their drug cargo (cisplatin) in the presence of matrix metalloproteinase 9, a protease overexpressed in tumors. In healthy tissues, matrix metalloproteinase 9 levels are too low to stimulate the release of the drugs, affording spatiotemporal control of drug release and potentially bypassing systemic side effects. The success of this technique in the ex vivo 3D lung tissue cultures of the present study has raised hopes that the same principles can be applied to other disease-specific enzymes.
Importantly, the joint project in association with the Nanosystems Initiative Munich Excellence Cluster has verified the application of selective drug transport in human tissue for the first time. Additionally, the research team were able to synergistically increase the therapeutic efficiency of the nanoparticles through the combinatorial drug delivery of cisplatin and the proteasome inhibitor bortezomib.
Silke Meiners (University of Munich, Germany) emphasized the significance of the work: “Using these nanocarriers we can very selectively release a drug such as a chemotherapeutic agent specifically at the lung tumor. We observed that the drug’s effectiveness in the tumor tissue was 10–25 times greater compared to when the drugs were used on their own. At the same time, this approach also makes it possible to decrease the total dose of medicines and consequently to reduce undesirable effects.”
Subsequent investigations are planned to substantiate the clinical efficacy of the nanocarriers in advanced lung tumor mouse models and to explore their safety in vivo.
Sources: van Rijt SH, Bölükbas DA, Argyo C et al. Protease-Mediated Release of Chemotherapeutics from Mesoporous Silica Nanoparticles to ex Vivo Human and Mouse Lung Tumors. ACS Nano doi:10.1021/nn5070343 (2015) [Epub ahead of print]; Helmholtz Zentrum München press release