This technology utilizes a DNA-templated micelle platform to selectively target the delivery of therapeutic drugs and genes to a wide range of cells.
Unmet Need: Consistent and efficient delivery of multiple therapeutic agents
As nanomedicine emerges as a solution in cancer treatment, the development of safe and consistent delivery platforms has become a prominent challenge. Nanoparticles can be formed into nanocarriers or conjugated to ligands for the delivery of chemotherapeutic agents. However, the use of nanocarriers brings a threat of nanotoxicity, in addition to resulting in inconsistent batch effects. Furthermore, concerns over loss of drug efficacy during encapsulation and delivery limit the scalability of the technology. As a result, there is continued demand for methods to effectively co-deliver multiple therapeutic cargoes.
The Technology: Nanoparticle micelle platform for efficient co-delivery of therapeutic agents
This platform implements DNA templates ligated to amine-functionalized polyethylene glycol (PEG) segments in order to form nanoparticle-sized micelles capable of efficiently delivering small nucleic acids and therapeutic drugs to target cells. The DNA bridge serves as modifiable template that can load siRNA, gRNA, mRNA, or drugs of interest, while the micelles can be conjugated with a customizable targeting peptide. Furthermore, this technology can be integrated into mesenchymal stem cell (MSC) spheroids for the direct delivery of cargo to tumors. The use of the DNA template allows not only heterogeneity within the micelle to carry multiple delivery agents, but also permits enhanced control over micelle formation, reducing the polydispersity and inconsistent batch effects.
This technology has been validated in vitro in cell lines and tumors.
Applications:
- Transfection method for in vitro cell lines
- Delivery platform for CRISPR/Cas9 system
- Delivery platform for therapeutic drugs and small nucleic acids
- Treatment method for cancer and heterogeneous tumors
- Research tool for targeting specific cell types
- Immunosuppressant therapy for autoimmune disorders
- Regenerative stem cell therapy after chemotherapy and relapse prevention
Advantages:
- Allows co-delivery of multiple therapeutic agents
- Compatible with multiple cargoes including mRNA, gRNA, siRNA, miRNA, PNA, DNAzyme, antisense nucleotides, and therapeutic drugs
- Increases efficiency of delivery of cargo directly to tumors
- Enhances control over nanoparticle micelle formation reducing polydispersity
- Enhances consistency between batches
- Easily customizable
- Enhances efficacy
- Reduces unwanted cytotoxicity
Lead Inventor:
Kam W. Leong, Ph.D.
Patent Information:
Patent Status
Related Publications:
Lao YH, Li M, Gao MA, Shao D, Chi CW, Huang D, Chakraborty S, Ho TC, Jiang W, Wang HX, Wang S, Leong KW. “HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute” Adv Sci. 2018 May 18; 5(7).
Zhang J, Li J, Shi Z, Yang Y, Xie X, Lee SM, Wang Y, Leong KW, Chen M. “pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities” Acta Biomaterialia. 2017 Aug; 58: 349-364.
Sun TM, Du JZ, Yao YD, Mao CQ, Dou S, Huang SY, Zhang PZ, Leong KW, Song EW, Wang J. “Simultaneous Delivery of siRNA and Paclitaxel via a ‘Two-in-One’ Micelleplex Promotes Synergistic Tumor Suppression” ACS Nano. 2011 Jan 4; 5(2): 1483-1494.
Leong KW, Mao HQ, Truong-Le VL, Roy K, Walsh SM, August JT. “DNA-polycation nanospheres as non-viral gene delivery vehicles” J Control Release. 1998 Apr 30; 53(1-3): 183-193.
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