Combination of small drugs and nucleic acid-based therapeutics, including genes and siRNA, represents an attractive approach for treatment of many diseases. Increasing evidence shows that the combination of therapeutic genes along with drugs can synergistically induce the apoptosis of cancer cells. However, the simultaneous delivery of small molecule drugs and genes into targeted cells has proved a significant challenge due to the differences in physicochemical properties of the two types of agents. There is an urgent need to develop a specific delivery system capable of co-delivering chemotherapeutic drugs and genes simultaneously with high efficiency for cancer therapy.
Technology Description
The present invention is a novel micellar system composed of cationic amphiphilic polymers for co-delivery of small molecule chemotherapy drugs and therapeutic genes. Researchers at the University of Pittsburgh have developed novel polymeric carriers composed of PEG hydrophilic segments and cationic moieties. These polymers have the ability to form micelles, which can effectively load hydrophobic drugs while simultaneously forming complexes with nucleic acids. When co-loaded with a drug and plasmid DNA, these micelles are observed to be significantly smaller and more stable than particles loaded with the drug alone. In this system, the multivalent charge–charge interactions between the cationic polymer and plasmid DNA serve as a simple approach to cross-link the micelles, thus making these micelles more stable than free micelles or micelles loaded with small molecule alone. As a working example, investigators developed a polymer for co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The use of this polymer resulted in significantly higher gene transfection in both lungs and tumors compared to control and, in addition to this improved anti-metastatic effect, synergistically enhanced the type I immune response and decreased immunosuppressive cells in the lung.
Advantages
* Ability to deliver therapeutic drugs simultaneously with drugs
* Produces a synergistic relationship to amplify effects
* Smaller and more stable than micelles loaded with drug alone
Applications
* Co-treatment of cancer via both chemical and genetic therapeutics
Stage of Development
In vivo, mice
IP Status
WO 2019/204799Relevant publications
Chen, Y et al (2019).
Targeted co-delivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis. Nanomedicine: Nanotechnology, Biology, and Medicine, 15, 129-141.
Xu, Jieni et al (2019).
Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis. Biomaterials, 25-40.
Song Li, MD, PhD
Professor, Pharmaceutical Sciences
Director, Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy
Dr. Li is a Professor at Department of Pharmaceutical Sciences the Director of the Center for Pharmacogenetics at the University of Pittsburgh School of Pharmacy. His research focuses on drug and gene delivery as well as gene regulation. He is an Associate Editor for the Journal of Gene Medicine and also serves on the editorial boards of several other journals. Research for Dr. Li’s lab has been supported by the NIH, DOD, and the American Heart Association (AHA).
Education
Postdoctoral, University of North Carolina at Chapel Hill
PhD, Fourth Military Medical University, Xi’An, China
MD, Fourth Military Medical University, Xi’An, China
Publications
* Chen, Y., Xia, R., Huang, Y., Zhao, W., Li, J., Zhang, X., Wang, P., Venkataramanan, R., Fan, J., Xie, W., Ma, X., Lu, B., and Li. S. An immunostimulatory nanocarrier that improves cancer immunochemotherapy. Nature Communication 7: 13443, 2016. (PMID: 27819653).
* Zhao, M., Huang, Y., Chen, Y., Xu, J., *Li, S., and *Guo, X. PEG-Fmoc-ibuprofen conjugate as a dual functional nanomicellar carrier for paclitaxel. Bioconjugate Chemistry 27: 2198-2205, 2016. (PMID: 27532881).
* Sun, J., Chen, Y., Li, K., Huang, Y., Zhang, X., Fu, X., Zhao, W., Wei, Y., Xu, L., Zhang, P., Venkataramanan, R., and Li, S. A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel. Acta Biomaterialia 43: 282-291, 2016 (PMID: 27422196).
* Zhang, P., Li, J., Ghazwani, M., Zhao, W., Huang, Y., Zhang, X., Venkataramanan, R., and Li, S. Effective co-delivery of doxorubicin and dasatinib using a PEG-Fmoc nanocarrier for combination cancer chemotherapy. Biomaterials 67: 104-114, 2015. (PMID: 26210177)
