Dual-Targeting Liposome-Based Drug Delivery System
It can be used as a novel, highly precise and effective TNBC therapy and as a platform to develop targeted therapeutics for other cancers
Background
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.
Technology Overview
Researchers at Boston Children’s Hospital 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.
Further Detail
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
Benefits
- 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
Applications
- Novel TNBC therapy that is highly precise and effective
- Platform to develop targeted therapeutics for other cancers
IP Status
- Patent application submitted
