Preferentially Delivering Cytotoxic Drugs to Cancer Cells
Our platform technology enables preferential delivery of cytotoxic drugs to cancer cells while sparing normal, healthy cells and tissues. At the same time, the technology delivers a lower systemic cytotoxic dose, minimizing both initial and long-term morbidity. Improving on the high tumor specificities already seen with ADCs, our novel format nano-ADCs like Targeted Nanospheres (nADC/TNS), provide a significantly greater on-target drug-to-antibody ratio (DAR) than ADCs.
Furthermore, the polyvalency of multiple antibodies attached to a single nADC/TNS enhances the overall avidity of the nanoparticles for targeting tumor cells compared to a single antibody-drug conjugate (ADC). Finally, the cytotoxic agents inside the hollow-shell nanoparticle are not chemically conjugated to the carrier. Once released from the carrier, no in situ chemical decoupling is required for the drug to become fully bioavailable.
Although nADC/TNPs were initially formulated for their stable drug loading characteristics, they also proved to be more therapeutically potent than their conventional liposome analogs. Once inside the target tumor cell, the cytotoxic drug in the nADC/TNP is released in the lysosome and diffuses to the nucleus, causing irreparable DNA damage and tumor cell death. [1]
nADC/TNSs provide a greater on-target drug-to-antibody ratio (DAR) than a traditional ADC: 1,000s of drug molecules per nanoparticle-conjugated antibody versus only 2 to 8 drug molecules per ADC antibody [2]. In addition, the polyvalency of many antibodies attached to a single nanoparticle enhances the nanoparticle’s overall avidity for targeting tumor cells compared to a single ADC molecule. Furthermore, encapsulation limits plasma concentrations of free drug and exposure to normal, healthy tissues.[1]
Reference
[1] Hyung-Gyoo Kang, Bryon Upton, Ryan W. Holly, Racheal Upton, Sheetal Mitra, Jean-Hugues Parmentier, Ann F. Mohrbacher, Yong-Mi Kim, Timothy J. Triche, Jon O. Nagy. Targeted Nanoparticles: an Innovative Modality in the Treatment of Cancer. (InPress/Prepress) bioRxiv 2025.12.01.691687; doi: https://doi.org/10.64898/2025.12.01.691687
[2] Maecker H, Jonnalagadda V, Bhakta S, Jammalamadaka V, Junutula JR. Exploration of the antibody-drug conjugate clinical landscape. MAbs. 2023 Jan-Dec;15(1):2229101. doi: 10.1080/19420862.2023.2229101. PMID: 37639687; PMCID: PMC10464553.
- Encapsulated payload options include small molecules, cytotoxics, therapeutics, and nucleic acids. (~ 60,000 drug molecules per nADC/TNS).
- Highly flexible targeting: conjugated agents can include human and mouse monoclonal antibodies (mAbs), peptides, and other targeting agents (~20 IgGs per nADC/TNS).
- Robust, nanoscale lipid particle shells serve as the base structure of an nADC/TNS. Adjusting cross-linking and polymer content provides favorable drug release (DMET and PK/PD).
- A proprietary lipo-polymer hybrid coat with two types of cores (aqueous and lipid) enables two classes of payloads: small molecules (aqueous) or nucleic acids (cationic lipids).
