A new study reported on a novel method of increasing the concentration of anticancer drugs at the site of the tumor, exploring a two-step nanoparticle delivery system for mesothelioma and other similar cancers in mice.
When a drug is given systemically by entering the blood stream, only a fraction of the drug reaches the target tissue. This is particularly true for mesothelioma and certain abdominal cancers where frequent intravenous or intraperitoneal injections of chemotherapy drugs need to be given to achieve sufficient concentrations at the site of the tumor.
The technique employs a two-step sequential approach. In the first step, a nanoparticle that can recognize the tumor is administered. These particles are taken up into tumor cells by being engulfed by part of the cell membrane that becomes internalized. Once inside, the particles expand tenfold, forming a gel particle made up of crosslinked polymers.
The expansion of the particles is pH-dependent; the membrane-enclosed sphere holding the particles has a lower pH than the rest of the cell, hence triggering the expansion. In the second step, the drug is administered and accumulates in the gel particles inside the cells.
Using both cultured mesothelioma cells and a mouse model of human mesothelioma, the researchers could show that the process worked in both model systems. The team used the mesothelioma drug paclitaxel – a chemotherapeutic agent that is very quickly removed from the body – to study the delivery system.
By labeling both the nanoparticle and the drug with fluorescent molecules of different colors, the team could follow the movements of the delivery system in both cultured cells and in living mice, confirming that both particles and drug ended up in the desired location.
The results showed that the concentration of paclitaxel in the cell-located gel particles were four times higher than in the surrounding aqueous environment. Following a single injection of paclitaxel, the drug remained in the tumor for up to three days – a time long enough to clear 99.9 percent of paclitaxel from the body without the delivery system.
The new method, which also differs from earlier nanoparticle-based methods by its two-step mechanism, has the potential to significantly improve mesothelioma treatment, and to ease the burden of frequent dosing for the patients.
The article, “Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles,“ by Aaron H. Colby and colleagues, was published in the journal Scientific Reports.