Nature-Inspired Nanoparticles for Therapeutics and Vaccine Delivery

Recent advances in nanotechnology have greatly boosted the development of novel delivery systems for therapeutic and vaccine applications, in particular highlighting the great success of lipid nanoparticle-based mRNA vaccines fast responding to the COVID-19 outbreak. To lead a successful nanomedicine technology, the key lies in the rational design and fabrication of safe and efficient nano-carries, while the delivery performance could be maximized by custom-designed nanoparticles considering the unique bio-interface configurations towards both cargo biomolecules and cell/tissue surfaces.
Mimicking the spiky morphology of pollen and virus, which allowed enhanced interactions at bio-interfaces, here, we showcase our recent progress in the development of spiky nanoparticle-based smart theranostics.^[1-4] Through a simple sol-gel synthesis approach, colloidal nanoparticles with an intrinsic spiky surface are fabricated and characterized by the advanced microscopy techniques of electron tomography.^[5] We demonstrated the precise control over the delicate nanotopography of spiky nanoparticles, engineering the surface chemistry,^[6] hollow interior,^[7] and asymmetry of the particles.^[8] We explored the interactions of these nature-inspired unique spiky nano-features towards both biomolecules and cells, gaining new understandings of the bio-nano-interfaces. Our findings underpinned the development of 1) a bacterial-adhesive antimicrobial nano-agent,^{[1, 9-11]} featuring an antibiotic-free approach to address the drug-resistance issue of infections; 2) a nano-burr hooking the rope-like DNA/mRNA molecules for efficient intracellular delivery,^[12] which allowed sufficient enzymatic protection of gene molecules and enabled of upregulated translation^[2]; 3) a pathogen mimetic adjuvant that boosts the vaccine delivery performance, ^[3] including our most recent study in developing DNA and subunit (RBD) spiky nano-vaccines for SARS-Cov-2.
From bench to market, this spiky nanoparticle-based delivery platform is on the translation collaborated with industrial partners toward novel nanomedicine. Our journey from fundamental research to the launching of ‘NUVEC^®’ will also be shared in this talk.


[1] H. Song, Y. A. Nor, M. H. Yu, Y. N. Yang, J. Zhang, H. W. Zhang, C. Xu, N. Mitter, C. Z. Yu*. J Am Chem Soc 2016, 138, 6455.
[2] H. Song, M. H. Yu, Y. Lu, Z. Y. Gu, Y. N. Yang, M. Zhang, J. Y. Fu, C. Z. Yu*. J Am Chem Soc 2017, 139, 18247.
[3] H. Song, Y. Yang,* J. Tang, Z. Gu, M. Zhang, C. Yu*. Adv Therapeutics 2020, 3, 1900154.
[4] D. Cheng, J. Zhang, J. Fu, H. Song*, C. Yu*. Sci Adv 2023, 9, eadi7502
[5] H. Song, Y. Yang, J. Geng, Z. Gu, J. Zou,* C. Yu*. Adv Mater 2019, 38, 1801564.
[6] J. Geng, H. Song,* F. Gao, Y. Kong, J. Fu, J. Luo, Y. Yang,*C. Yu. J Mater Chem B 2020, 8, 4593.
[7] E. Hines, D. Cheng, W. Wu, M. Yu, C. Xu, H. Song,* C. Yu.* J Mater Sci 2021, 56: 5830.
[8] X. Lin, W. Wu, J. Fu, Y. Yang, B. Guo, C. Yu,* H. Song*. ACS Appl Mater Interfaces 2021, 13: 50695.
[9] B. Li, Y. Liao, X. Su, S. Chen, X. Wang, B. Shen, H. Song*, P. Yue*. J Nanobiotech 2023, 21: 325.
[10] M. Zhang, J. Feng, Y. Zhong, J. Luo, Y. Zhao, Y. Yang, Y. Song, X. Lin, Y. Yang,* H. Song,* C. Yu.* Chem Eng J 2022, 440: 125837.
[11] Y. Wang, Y. Yang, Y. Shi, H. Song,* C. Yu* Adv Mater 2020, 32: 1904106.
[12] B. Sun, W. Wu, E. Narasipura, Y. Ma, O. Fenton,* H. Song.* Adv Drug Del Rev 2023, 200: 115042.