Dual-targeting liposome-based drug delivery system
Inventors: Marsha Moses, Peng Guo
Invention Types: Therapeutics
Research Areas: Oncology/Hematology
Keywords: Animal Model (mouse), Drug Delivery, Gene expression, Receptor/Ligand, Cell Signaling, Drug Design, PlatformFor More Information Contact: Wong, Adrienne
A major challenge in cancer treatment is discriminating malignant cancer cells from normal cells. “Cancer-targeting” liposomes have been engineered to facilitate the specific recognition of cancer, but have had limited success due to “off-target” effects.
Dr. Marsha Moses and collaborators have developed a novel liposome delivery system that exploits the overexpression of cell surface proteins on cancer cells by recognizing and complementing their molecular density. These dual complementary liposomes (DCLs) have a double therapeutic effect on cancer cells: first, they facilitate targeted delivery of a drug to cancer cells; second, they neutralize the signaling cascades triggered by cell surface proteins to inhibit cell invasion and proliferation.
Proof-of-concept studies have been performed with triple negative breast cancer (TNBC) cells. Doxorubicin-loaded DCLs with conjugated ligands targeting ICAM1 and EGFR are more efficiently internalized by TNBC cells in vitro than single-target liposomes, efficiently and specifically kill the malignant cells, and reduce proliferation and invasion. Furthermore, the DCLs were pre-clinically validated in an orthotopic mouse model in which they inhibited tumor growth and metastasis while increasing survival.
The DCL platform can be customized to target other cancers and deliver a variety of payloads. Using a combination of proteomic and genetic screening, a truly personalized and cell-specific therapeutic could be created to improve outcomes for cancer patients.
• Novel TNBC therapy that is highly precise and effective
• Platform to develop targeted therapeutics for other cancers
• A customizable system based on proteomic and genetic screening to optimize target combinations for specific cancer sub-types
• DCL’s are engineered to provide specific and cooperative adhesion force that are not provided by existing methods
• Synergistic effect of drug cargo and cell signaling inhibition of DCLs
License, sponsored research, collaboration
Key Publications: Guo P†, Yang J†, Liu D, Huang L, Fell G, Huang J, Moses MA‡, Auguste DT‡. Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis. Sci Adv 2019;5:eaav5010. † Contributed equally. ‡ Contributed equally. https://doi.org/10.1126/sciadv.aav5010
IPStatus: Pat. Pend.