Gaeun Kim, Runyao Zhu, Sihan Yu, Bowen Fan, Hyunsu Jeon, Jennifer Leon, Matthew J Webber, Yichun Wang
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引用次数: 0
Abstract
Small extracellular vesicles (sEVs) are promising nanocarriers for drug delivery to treat a wide range of diseases due to their natural origin and innate homing properties. However, suboptimal therapeutic effects, attributed to ineffective targeting, limited lysosomal escape, and insufficient delivery, remain challenges in effectively delivering therapeutic cargo. Despite advances in sEV-based drug delivery systems, conventional approaches need improvement to address low drug-loading efficiency and to develop surface functionalization techniques for precise targeting of cells of interest, all while preserving the membrane integrity of sEVs. We report an enhanced gene delivery system using multifunctional sEVs for highly efficient siRNA loading and delivery. The integration of chiral graphene quantum dots enhanced the loading capacity while preserving the structural integrity of the sEVs. Additionally, lysosomal escape is facilitated by functionalizing sEVs with pH-responsive peptides, fully harnessing the inherent homing effect of sEVs for targeted and precise delivery. These sEVs achieved a 1.74-fold increase in cytosolic cargo delivery compared to unmodified sEVs, resulting in substantial gene silencing of around 73%. Our approach has significant potential to advance sEV-based gene delivery in order to accelerate clinical progress.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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