Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

Aza-BODIPY-based phototheranostic nanoagent for tissue oxygen auto-adaptive photodynamic/photothermal complementary therapy

Tumor oxygen spatial heterogeneity is a critical challenge for the photodynamic inhibition of solid tumors.Development of an intelligent nanoagent to initiate optimal therapeutics according to the localized oxygen levels is an effective settlement.Herein,we report an activatable nanoagent(BDP-Oxide nanoparticles(NPs))to enable the oxygen auto-adaptive photodynamic/photothermal complementaly treatment.Upon the nanoagent accumulated in the tumor region,the low extracellular pH could trigger the disassociation of the nanoagent to release the phototheranostic agent,BDP-Oxide,which will subsequently afford the fluorescence imaging-guided photodynamic oxidation after it gets into the outer oxygen-rich tumors.Along with the penetration deepening in the solid tumor,furthermore,BDP-Oxide could be reduced into BDP by the cytochrome P450(CYP450)enzymes activated in the low oxygen tension regions of inner hypoxic tumors,which will switch on the photothermal and photoacoustic effects.Overall,the BDP-Oxide NPs-enabled photodynamic/photothermal complementary therapy significantly suppressed the solid tumor growth(inhibition rate of 94.8%).This work proposes an intelligent platform to address the oxygen partial pressure for the optimization of cancer phototherapeutics.