Functionalized Blood Small Extracellular Vesicles with Polydopamine Nanoparticles for Chemo-Thermal Therapy.

Small extracellular vesicles (sEVs) hold considerable promise for drug delivery due to their natural origin and inherent qualities. However, their clinical application is impeded by two main challenges: low yield and potential side effects. Therefore, it is crucial to obtain substantial quantities of sEVs that adhere to rigorous biosafety standards to ensure successful translation into clinical practice. To address this need, we propose exploring optimized methods for sourcing and separating sEVs, taking inspiration from clinical blood transfusion. In particular, we have identified blood sEVs as a viable alternative and developed a novel separation technique for their isolation. Our approach involves incubating dopamine solution with serum, resulting in the formation of polydopamine (PDA) nanoparticles on the surface of blood sEVs. These nanoparticles have minimal impact on blood sEVs, facilitating their easy separation under standard centrifugal conditions with high purity. This innovative technique enables the development of nanocarriers using blood sEVs with efficient drug-loading capabilities and enhanced pharmacokinetics. Additionally, the incorporation of PDA nanoparticles imparts a photothermal effect to the nanomedicines, enabling the integration of chemotherapy and photothermal therapy. Moreover, the photothermal effect holds the potential to facilitate the membrane fusion of sEVs and cells. In summary, our straightforward surface functionalization technique utilizing PDA effectively isolates blood sEVs and enables chemo-thermal tumor therapy. This approach significantly enhances the feasibility of translating sEV-based nanomedicines into clinical applications.