Delivering chemotherapy with a lighter touch
Despite significant improvements in cancer diagnosis and treatment, cases are predicted to rise by around 70 % over the next two decades as a result of an ageing and growing population. Cancer treatment is often based on intravenous (IV) chemotherapy, which usually requires hospitalisation and can be very uncomfortable for patients. One promising alternative is subcutaneous (SC) chemotherapy, where drugs are inserted just below the skin. The THERMONANO project, which was funded by the European Research Council, developed new treatments based on drug-polymer conjugates, nanomedicines which can be delivered via a simple SC administration. “We sought to develop a chemotherapy strategy that is more comfortable and less dangerous for the patient, and also less costly, to significantly decrease the financial burden on patients and healthcare systems,” explains Julien Nicolas, French National Centre for Scientific Research (CNRS) research director at the Galien Paris-Saclay Institute in France and THERMONANO project coordinator.
Building sophisticated nanocarriers
While SC injectables are more comfortable for patients and allow them to self-administer at home, most of the anticancer nanocarriers currently developed are not suitable for SC administration, as early release of the anticancer drugs causes local toxicity at the injection site. Sophisticated nanocarriers are difficult and expensive to build, and despite encouraging results there are few examples of successful treatments. The THERMONANO team developed a scalable approach for the SC administration of anticancer drugs. The drug delivery system is made of one anticancer drug molecule attached at the extremity of a well-defined, water-soluble biocompatible polymer chain. Nicolas has been working on the design, synthesis and evaluation of polymeric prodrugs for the last 10 years, in particular on the approach of growing the polymer from the drug in a controlled manner. This approach – the ‘drug-initiated’ method – is flexible, easy to perform, requires only a few synthetic steps and gives high yields. “During this project, we have applied this approach to the synthesis of water-soluble polymer prodrugs and carried out their comprehensive preclinical evaluation,” adds Nicolas. Through the project, the new polymer prodrugs were evaluated for several properties, including their SC injectability, drug release abilities, toxicity on two different cancer cell lines, and anticancer efficacy. “We demonstrated that our polymer prodrugs could be safely injected subcutaneously without inducing local toxicity, while outperforming a commercial competitor version for IV administration. This opens the door to the safe transposition from IV to SC chemotherapy,” says Nicolas.
Founding a start-up
Owing to the promising results achieved during the project, the THERMONANO team, along with several colleagues, founded the start-up Imescia to advance the technology. The enterprise aims to find industrial partners who could use the technology to administer drug molecules in SC, and to bring a first treatment into clinical trials as early as 2024. Imescia is currently seeking funding. “The overall idea is to apply this strategy to a very wide range of anticancer drugs (not just small molecules) and thus safely and effectively transpose IV chemotherapies to SC chemotherapies,” says Nicolas. “We hope that this new administration platform will represent an important step towards simplified chemotherapy, enabling patients to be managed at home, or even to self-administer their treatments.”
Keywords
THERMONANO, cancer, subcutaneous, nanocarriers, nanomedicine, start-up, design, treatment, diagnosis