Kinetically controlled assembly and scalable production of nanoparticles for delivery of biologic therapeutics

We have invented a new flash nanocomplexation (FNC) process for scalable production of polyelectrolyte complex nanoparticles (US patent issued in 2019); and applied this method to kinetically control the packaging of various type of nucleic acids (Santos, et al, 2016), protein therapeutics (He, et al, 2017, 2018, Nie, et al, 2019, Hanwright et al, 2022), small molecular weight drugs (Li, et al, 2022), and vaccines (Qiao, et al, 2018). Recently, we have extended this method to assemble uniform, stable, and off-the-shelf particles within the size range of 200 to 900 nm to enhance the co-delivery efficiency of different virus packaging plasmids, and improve the lentivirus production efficiency (Hu, et al, 2021).  


  1. Santos JL, Ren Y, Vandermark J, Archang MM, Williford JM, Liu H, Lee J, Wang TH, Mao HQ. Continuous production of discrete plasmid DNA-polycation nanoparticles using flash nanocomplexation. Small. 12(45): 6214–6222 (2016). PMCID: PMC5149445; PMID: 27717227.
  2. He Z, Santos JL, Tian H, Huang H, Hu Y, Liu L, Leong KW, Chen Y, Mao HQ. Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin. Biomaterials. 130: 28–41 (2017). PMID: 28359018.
  3. Hu Y, He Z, Hao Y, Gong L, Pang M, Howard GP, Ahn HH, Brummet M, Chen K, Liu HW, Ke X, Zhu J, Anderson CF, Cui H, Ullman CG, Carrington CA, Pomper MG, Seo JH, Mittal R, Minn I, Mao HQ. Kinetic control in assembly of plasmid DNA/polycation complex nanoparticles. ACS Nano. 13 (9): 10161–10178 (2019). PMCID: PMC7293580; PMID: 31503450.
  4. Hu Y, Zhu Y, Sutherland ND, Wilson DR, Pang M, Liu E, Staub JR, Berlinicke CA, Zack DJ, Green JJ, Reddy SK, Mao HQ. Size-controlled and shelf-stable DNA particles for production of lentiviral vectors. Nano Lett. 21(13): 5697–5705 (2021). PMCID: PMC8283758; PMID: 34228937.
  5. Hanwright PJ, Qiu C, Rath J, Zhou Y, von Guionneau N, Sarhane KA, Harris TGW, Howard GP, Malapati H, Lan MJ, Reddy S, Hoke A, Mao HQ, Tuffaha SH. Sustained IGF-1 delivery ameliorates effects of chronic denervation and improves functional recovery after peripheral nerve injury and repair. Biomaterials. 280: 121244 (2022). PMID: 34794826.
  6. Li S, Hu Y, Li A, Lin J, Hsieh K, Schneiderman Z, Zhang P, Zhu Y, Qiu C, Kokkoli E, Wang TH, Mao HQ. Payload distribution and capacity of mRNA lipid nanoparticles. Nature Communications. 13(1): 5561. doi: 10.1038/s41467-022-33157-4. PMID: 36151112; PMCID: PMC9508184 (2022).