Nanomedicine, driven by the success of lipid nanoparticle-based mRNA vaccines developed during the COVID-19 pandemic, which highlighted the huge clinical potential of nanoscale delivery systems and accelerated their translation, has gained remarkable attention worldwide. Within this rapidly evolving field, hybrid nanoparticles, combining the structural versatility of polymers with the biocompatibility and biomimetic properties of lipids, represent a promising platform to overcome the limitations of conventional nanocarriers [1,2].

The rational design and engineering of polymer–lipid hybrid nanoparticles (PLHNs), highlighting their unique physicochemical features, including tunable size, surface functionalization for targeting strategies, mechanical stability and controlled drug release profiles will be discussed [3]. A particular focus will be placed on the synergistic interplay between polymeric cores and lipid shells, which enables improved encapsulation efficiency of different payloads (such as small molecules, genetic materials, etc), enhanced circulation time and reduced immunogenicity. The emerging trends in the field will be also addressed, focusing the attention on the integration of stimuli-responsive polymers in PLHNs to improve the both the efficacy and the selectivity of the payloads, especially in the treatment of chronic disease such as cancer or neurodegenerative disorders [4]. Moreover, the recent advances in the formulation strategies of PLHNs, including the microfluidic-assisted techniques may further improve their clinical translation by offering a scalable and standardizable production. By bridging the gap between polymer chemistry and lipid nanotechnology, hybrid nanoparticles hold the potential to improve the landscape of precision medicine, providing tailored therapeutic solutions.

References

1- M. Alawi, A.R. Hilles, M. Kumar, M.D. Ansari, S. Mahmood Nanomedicine 2025, 20, 1775.

2- Q. Saiding, F. Xiao, M.M. Khan, N. Kong, X. Huang, W. Tao Acc Chem Res. 2026, 59, 762.

3- A. Rocchi, V. Sidorenko, N. d'Avanzo, L. Marchetti, J. Sethi, L. Ciriolo, A.M. Tolomeo, M.G. Cifone, P. Palumbo, M. Fresta, T. Teesalu, C. Celia ACS Pharmacol. Transl. Sci. 2025, 8, 3654.

4- H. Sarma, A. Dutta, A. Bharali, S.S. Rahman, S. Baruah, N. Biswas, B.P. Sahu Drug. Dev. Ind. Pharm. 2024, 50, 856.