Vesicle-Mediated Delivery of Carbon Dots: Synthesis, Properties, and Biomedical Applications

Carbon dots (CDs), as an emerging class of carbon nanomaterials, exhibit exceptional optical properties, biocompatibility, and functional tunability, rendering them highly promising for applications in biosensing, bioimaging, antibacterial therapy, and phototherapy. However, their small size leads to a poor enhanced-permeation-and-retention (EPR) effect and inadequate targeting capability, which hinders their further translation into biomedical applications. Vesicles, including natural extracellular vesicles (EVs), liposomes, and synthetic vesicles, serve as ideal nanocarriers due to their unique bilayer structure, excellent biocompatibility, and intrinsic targeting properties. The integration of CDs with vesicles forms a novel multifunctional hybrid system, which can effectively address the delivery limitations of CDs while endowing vesicles with additional functionalities such as fluorescence tracing and phototherapeutic effects. This review systematically summarizes the synthesis methods (top-down and bottom-up) and key physicochemical (structural and optical) properties of CDs, as well as the classification and characteristics of various vesicles. Furthermore, it focuses on the construction strategies, interaction mechanisms, and loading methods of CD-vesicle hybrids, and comprehensively elaborates on their applications in targeted drug delivery, bioimaging, tumor therapy, antibacterial treatment, and wound healing. In addition, we critically discuss the key bottlenecks currently limiting the clinical translation of CD-vesicle hybrid therapeutics, including the thermodynamic limitations of drug/CD loading efficiency, burst release of payloads, in vivo pharmacokinetic behavior, and the effects of CDs on vesicle interfacial stability and leakage kinetics. Finally, the current challenges (e.g. unclear interaction mechanisms, limited scalable production, and narrow application scope) and future development directions (e.g. expanding antimicrobial applications, promoting clinical translation, and exploring CD self-assembled vesicles) of CD-vesicle hybrid systems are discussed, aiming to provide a comprehensive reference for the rational design and biomedical application of CD-vesicle hybrid nanomaterials.