Nanoengineering of Exosomal Surfaces for Precision Targeting and Payload Delivery at the Molecular Level

Area of Science:

• Biotechnology
• Nanomedicine
• Cell Biology

Background:

• Exosomes are nano-sized vesicles with therapeutic potential due to biocompatibility and low immunogenicity.
• Native exosomes exhibit heterogeneity and limited targeting specificity, hindering clinical translation.
• Advanced engineering is crucial to optimize exosome-based therapies.

Purpose of the Study:

• To review molecular-level nanoengineering strategies for exosome surface modification.
• To enhance exosome specificity, payload loading efficiency, and release control.
• To provide a framework for designing engineered exosomes for clinical success.

Main Methods:

• Genetic modification of parent cells.
• Covalent and non-covalent surface conjugation of targeting ligands (peptides, aptamers, nanobodies, glycans).
• Lipid insertion, click chemistry, and hybrid vesicle fusion for exosome engineering.

Main Results:

• Detailed quantitative performance of various targeting ligands and conjugation methods.
• Critical analysis of endogenous and exogenous payload loading techniques.
• Highlighting disease-specific applications in oncology, neurology, cardiology, and immunotherapy.

Conclusions:

• Molecularly engineered exosomes offer a promising platform for targeted drug delivery and therapy.
• Emerging technologies like AI and microfluidics will advance precision exosome development.
• Addressing challenges in scalability and standardization is key for clinical translation.