Three Research Teams Advance Nanoparticle Platforms for Targeted Cancer Therapy
Scientists at three institutions have developed distinct nanoparticle-based drug delivery systems designed to target cancer tumors more precisely while reducing side effects, with approaches ranging from DNA nanomachines to transformable nanofibers.
Three separate research teams have developed novel nanoparticle-based strategies aimed at delivering cancer treatments more precisely to tumors while minimizing damage to healthy tissue.
A team at Zhujiang Hospital, Southern Medical University, led by Professor Chao Zhang, has developed a DNA nanomachine-based drug delivery system to overcome chemoresistance in small cell lung cancer (SCLC). The team identified the PRMT1/SOX2 signaling axis as a key driver of chemotherapy resistance in SCLC and designed a DNA nanomachine capable of temporally programmed drug release. The system simultaneously loads the PRMT1 inhibitor DCLX069 and cisplatin, enabling a programmed therapeutic sequence within tumor cells: rapid release of DCLX069 to suppress tumor stemness, followed by gradual release of cisplatin to maximize cytotoxic efficacy.
The findings showed that PRMT1 is markedly upregulated in chemoresistant SCLC cells and closely correlated with poor patient prognosis. Mechanistic studies revealed that PRMT1 promotes chemoresistance by activating SOX2-mediated tumor stemness. Inhibition of PRMT1 significantly reduced stemness and enhanced sensitivity to cisplatin. The DNA nanomachine demonstrated excellent tumor-targeting capability both in vitro and in vivo. In cellular and animal models, the nanotherapeutic system effectively reversed chemoresistance in SCLC and significantly inhibited tumor growth. Compared with conventional intravenous cisplatin administration, the DNA nanomachine markedly reduced cisplatin-associated hematological and renal toxicity and did not induce obvious immunogenic responses. The research was published in the journal Research.
Scientists at McGill University and the Rosalind and Morris Goodman Cancer Institute have developed a different approach to deliver cancer immunotherapy designed to treat cancer that has spread to the lymph nodes. Researchers packaged an existing immunotherapy drug into engineered nanoparticles that travel through the bloodstream and release and activate the drug when they reach lymph nodes affected by cancer. The nanoparticles can sense a molecule that's abundant in cancerous lymph nodes and activate the drug exactly where it's needed, while in healthy tissues, the drug remains inactivated and eventually degraded, according to the Canada Research Chair in Biomaterials and Biomacromolecule Delivery.
Published in the Proceedings of the National Academy of Sciences (PNAS), results from mouse models demonstrate the nanoparticles reduced harmful side effects and improved effectiveness compared with standard IV immunotherapy. The experimental approach is designed to address a key challenge: lymph nodes affected by cancer are often surgically removed, a step that can weaken the immune system. The team is now evaluating safety in other preclinical studies before initiating any clinical trials.
UC Davis Comprehensive Cancer Center scientists are testing transformable nanoparticles that travel through the body as tiny particles and then reshape into nanofiber networks when reaching cancer sites. These fibers cling to tumors but naturally fade away much more quickly in healthy organs, creating a built-in targeting system. The work is being led by Distinguished Professor Kit S. Lam with the UC Davis Health Department of Biochemistry and Molecular Medicine and the Division of Hematology and Oncology. The research recently received a $3.1 million National Institutes of Health (NIH) R01 research project grant.
Once the nanoparticles form a web of tiny fibers around a tumor, researchers can deliver therapeutic molecules using a highly specific "click chemistry" reaction. This second step allows clinicians to add medicines on demand — including small-molecule drugs, toxins, and immune-boosting molecules or proteins — that can augment the anti-tumor effects of the immune system. The nanoparticles can stay in tumor areas for up to a week but fade from healthy organs like the liver and lungs within just two days.
The UC Davis team refers to this as a two-component, two-step strategy: the nanoparticles locate the tumor and transform into a long-lasting molecular framework, then doctors administer therapeutic agents that lock onto the drug delivery system and begin working within the tumor microenvironment. The project includes three major goals: design and refine nanoparticles that target receptors found in cancers such as non-small cell lung cancer; use advanced imaging to understand how the nanoparticles behave in living systems; and test the safety and effectiveness of this approach in preclinical cancer models.