Bottlebrush Nanoparticles Deliver High-Dose Chemotherapy Directly to Tumors

Chemotherapy is a powerful tool in the fight against cancer, but its systemic delivery often causes severe side effects. Researchers at MIT have developed a new type of nanoparticle that may solve this problem by delivering large doses of chemotherapy drugs directly to tumor cells while sparing healthy tissue.

These particles are shaped like bottlebrushes and are engineered to carry hundreds of drug molecules. Each particle is tethered to an antibody that targets specific proteins found on cancer cells, such as HER2 in breast cancer or MUC1 in ovarian and lung cancers. This design allows the particles to home in on tumors and release their payload precisely where it is needed.

Traditional antibody-drug conjugates (ADCs) can only carry a few drug molecules per antibody, limiting their effectiveness to highly potent drugs. MIT’s bottlebrush particles, known as antibody-bottlebrush conjugates (ABCs), overcome this limitation by attaching dozens or even hundreds of prodrug molecules to each antibody. These prodrugs are inactive until they reach the tumor site, where they are activated by cleavable linkers.

In mouse models of breast and ovarian cancer, the ABCs were able to eliminate most tumors using doses nearly 100 times lower than conventional chemotherapy. The treatment also outperformed two FDA-approved ADCs, T-DXd and TDM-1, which are currently used to target HER2-positive cancers.

The researchers tested a variety of drugs with the ABC system, including microtubule inhibitors, DNA-damaging agents, and experimental compounds known as PROTACs. They also demonstrated the ability to combine multiple drugs within a single particle, opening the door to personalized combination therapies.

Looking ahead, the team plans to explore additional antibody targets and drug combinations, including immunotherapy agents. With more than 100 antibodies already approved for clinical use, the potential for customizing this platform is vast.