Antibody-drug conjugates (ADCs) have very clear advantages in targeted administration, but they are not sufficient to overcome the dosing limitations of tumor heterogeneity.
Recently, a joint team from Cornell University, the Sloan Kettering Cancer Institute and a tumor drug company took a molecular engineering path to develop a conjugate (NDC) composed of ultra-small (less than 10 nanometers) nanoparticles-drugs, which have many similarities with ADCs and have significant advantages in overcoming tumor heterogeneity. The results were published online on April 22 in Materials Chemistry.
The research team said the key challenges of NDC development include the chemical design of the connection between nanoparticle carriers and cytotoxic drugs, as well as meeting stringent standards for manufacturing control, stability and drug release. Only by solving these key links can the clinical translation of NDCs be successfully realized.
In this study, the research team used relevant chemical methods and molecular engineering methods to covalently connect chemotherapeutic drugs and targeted parts to a polyethylene glycol (PEG) coating-coated ultra-small silica nanoparticle platform to form conjugates by precisely adjusting the particle surface chemistry. This method utilizes the gap between PEG strands on the surface of the particles to load the drug, and this conjugate significantly enhances the drug loading capacity compared to ADCs while maintaining good biological distribution and pharmacokinetic characteristics.
In order to achieve high plasma stability and effective drug release in cancer treatment, the scientific team conducted relevant tests, inserting cyclopentadiene silane molecules into the PEG layer of the particles and condensing with the silanol groups on the surface of the silicon core. By further reaction, the cyclopentadiene group is then functionalized, thus achieving click chemistry, and the cytotoxic payload is finally clicked onto the particle by a cleavable linker, achieving the release of the drug within the cancerous tissue.
Nanoparticles – drug-composed conjugates can be used for tumor-targeted therapy. Image from the paper
The research team said that the NDC-targeted drug produced by the study has recently entered phase I and II human clinical trials. (Source: China Science Daily Zheng Jinwu)
Related paper information:https://doi.org/10.1021/acs.chemmater.1c04447