In a new study entitled “Protease Mediated Release of Chemotherapeutics From Mesoporous Silica Nanoparticles to Ex Vivo Human and Mouse Lung Tumors” researchers engineered nanoparticles loaded with chemotherapeutics that specifically target and deliver therapy into lung tumor cells. The study was published in the journal ACS Nano.
Tumor tissues often express cancer-specific proteins or proteins that are particularly overexpressed. Advanced lung tumors express high levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9), while in healthy tissue their expression is significantly lower. In fact, these proteases (enzymes that cut specific proteins) are associated with enhanced metastasis and tumor progression.
Since they have a specific enzymatic activity towards certain proteins, a research team at Comprehensive Pneumology Center (CPC) and colleagues from the Department of Chemistry and Center for NanoScience (CeNS), University of Munich, devised nanoparticles (mesoporous silica nanoparticles), carrying chemotherapy drugs, with a coat of proteins that can only be cleaved by MMP9 proteases. The strategy allowed the specific delivery of drug-loaded nanoparticles to lung tumors highly-expressing MMP9, leaving healthy tissues unharmed. The authors could successfully confirm the delivery of these nanoparticles to both human tumor cells and mouse/human lung tumors through ex vivo 3D technology in lung tissue cultures.
The team used the nanoparticles to deliver cisplatin, a chemotherapeutic drug, and observed the induction of specific cancer cell death in lung tumors of Kras mutant mice. The strategy also proved efficient in delivering both cisplatin and bortezomib, a proteasome inhibitor, enhancing the anti-tumor effect of the therapeutics. Notably, the MMP9-regulated drug release of both cisplatin (alone) or in combination with bortezomib did not affect tumor free areas or even healthy mice.
The team is now engaged in translating their findings to an in vivo setting and assessing the systems’ efficacy in mouse models of advanced lung cancers.
Silke Meiners, principal investigator of the research group and study lead author commented in a press release, “Using these nanocarriers we can very selectively release a drug such as a chemotherapeutic agent specifically at the lung tumour. We observed that the drug’s effectiveness in the tumour tissue was 10 to 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.”