RESEARCH

Nanoparticle-mediated delivery of nucleic acid therapeutics

Nanoparticles remain the most versatile delivery vehicle for gene medicine. We have developed important strategies to improve nanoparticle engineering and delivery efficiency, and contributed to better understandings of the delivery barriers for non-viral gene delivery.  Our first set of papers on this topic have established the methods on preparing DNA nanoparticles based on complex coacervation using natural polymers including chitosan (Roy, et al. 1999; Mao, et al., 2001) and gelatin (Truong-Le, et al, 1999), and tailor-designed biodegradable polyphosphoesters (Wang, et al, 2001).  We have first demonstrated the efficacy of chitosan-DNA nanoparticles as a carrier for genetic immunization through oral immunization (Roy, et al. 2009).  This study also provided the momentum for developing gene therapy strategies for mucosal gene delivery and genetic immunization (Chew, et al, 2003).  In addition, we have demonstrated retrograde intrabiliary infusion (RII) method as an effective administration route for liver-targeted gene delivery of DNA nanoparticles (Dai, et al, 2006; 2011).  This approach takes advantage of the unique biliary architecture leading to direct access of nanoparticles to the liver parenchymal cells.  Using SPECT/CT imaging method, we characterized DNA transport kinetics following intrabiliary infusion as compared with intravenous injection (Patil, et al, 2011).  This study provided key insight into the mechanism by which DNA nanoparticles transfect liver parenchymal cells and other cells and tissue, and confirmed that RII is the most efficient route for liver-targeted gene delivery, comparing with intravenous injection and portal vein infusion.  This method can be easily adopted in clinical settings via endoscopic retrograde cholangiopan-creatography (ERCP), a routine bile duct canulation procedure.

Publications

  1. Mao HQ, Roy K, Troung-Le VL, Janes KA, Lin KY, Wang Y, August JT, Leong KW. (2001). Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J. Control. Release. 70(3): 399-421. PMID: 11182210.
  2. Roy K, Mao HQ, Huang SK, Leong KW. (1999). Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat. Med. 5(4): 387-391. PMID: 10202926.
  3. Patil RR, Yu J, Banerjee SR, Ren Y, Leong D, Jiang X, Pomper M, Tsui B, Kraitchman DL, Mao HQ. (2011). Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging. Mol. Ther. 19(9): 1626-1635. PMID: 21750533; PMCID: PMC3182352.
  4. Williford JM, Archang MM, Minn I, Ren Y, Wo M, Vandermark J, Fisher PB, Pomper MG, Mao HQ. (2016). Critical length of PEG grafts on lPEI/DNA nanoparticles for efficient in vivo delivery. ACS Biomater. Sci. Eng. 2(4): 567–578. PMID: 27088129.