Cucumber‐Derived Extracellular Vesicle‐Functionalized Metal‐Organic Frameworks for Enhanced Photodynamic Therapy of Hypertrophic Scars

Abstract

Photodynamic therapy (PDT) with noninvasiveness and high safety has emerged as a promising therapeutic approach for the management of hypertrophic scars (HS). However, the low transdermal delivery and overexpressed levels of intracellular glutathione (GSH) severely hinder its therapeutic effectiveness. Herein, a multifunctional biomimetic nanoplatform (NDs@EV‐RGD) composed of arginine‐glycine‐aspartic acid (RGD)‐modified cucumber‐derived extracellular vesicles (EVs) and copper‐based metal‐organic framework nanodots (Cu‐MOF NDs) is designed for PDT‐mediated HS treatment. The EVs with low Young's modulus exhibit excellent deformability which endow NDs@EV‐RGD with the capacity to overcome the compact stratum corneum barrier, thereby significantly improving their transdermal delivery efficiency. Notably, the RGD targeting peptide displays specific binding to α1β1 integrin on the fibroblast membranes within HS, leading to the high accumulation efficiency of NDs@EV‐RGD at the HS site. Under near‐infrared laser irradiation, NDs@EV‐RGD efficiently generates abundant reactive oxygen species, inducing the apoptosis of excessively proliferated fibroblasts. Moreover, Cu‐MOF NDs interact with the local GSH, leading to GSH depletion and a significant enhancement in PDT efficacy. Furthermore, NDs@EV‐RGD demonstrates a remarkable therapeutic effect in improving the appearance of HS in a rabbit ear HS model, promoting the apoptosis and remodeling of collagen fibers. Therefore, this work provides a promising biomimetic platform for HS treatment.

Fluorinated Titanium Oxide (TiO2–xFx) Nanospindles as Ultrasound-Triggered Pyroptosis Inducers to Boost Sonodynamic Immunotherapy

“…Light and US, as indispensable energy sources in minimally invasive surgery, have provided a firm basis for their clinical application. Photodynamic therapy (PDT) and SDT are therapeutic modalities that necessitate the use of photosensitizers and sonosensitizers, which was stimulated by light and US, respectively. , However, the depth of tissue penetration by light or US is deemed as a pivotal determinant in attaining favorable therapeutic results. Since TiO 2 is also an excellent photocatalytic material that can be used in PDT, the potential of TiO 2– x F x as a photosensitizer and a sonosensitizer for PDT or SDT has been further evaluated .…”