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.

Synchronous detection of glutathione/hydrogen peroxide for monitoring redox status in vivo with a ratiometric upconverting nanoprobe

Cellular redox status presents broad implications with diverse physiological and pathological processes. Simultaneous detection of both the oxidative and reductive species of redox couples, especially the most representative pair glutathione/hydrogen peroxide (GSH/H2O2), is crucial to accurately map the cellular redox status. However, it still remains challenging to synchronously detect GSH/H2O2 in vivo due to lack of a reliable measuring tool. Herein, a ratiometric nanoprobe (UCNP-TB) possessing simultaneous delectability of GSH/H2O2 is established based on a multi-spectral upconverti ng nano phosphor (UCNP-OA) as the lumin esce nee res onance energy tran sfer (LRET) donor and two dye molecules as the acceptors, including a GSH-sensitive dye (TCG) and a H2O2-sensitive dye (BCH). With the as-prepared UCNP-TB, real-time and synchronous monitoring the variation of GSH and H2O2 in vitro and in living mice can be achieved using the ratio of the upcon versi on lumin esce nee (UCL) at 540 and 650 nm to that at 800 nm as the detecti on sign al, respectively, providi ng highly inhere nt reliability of the sensing results by self-calibrati on. Moreover, the nan oprobe is capable of mappi ng the redox status within the drug-resista nt tumor and the drug-induced hepatotoxic liver via ratiometric UCL imaging. Thus, this nan oprobe would provide a reliable tool to elucidate the redox state in vivo.

Light-responsive charge-reversal nanovector for high-efficiency in vivo CRISPR/Cas9 gene editing with controllable location and time

Controllably and efficaciously localized CRISPR/Cas9 plasmids transfection plays an essential role in genetic editing associated with various key human diseases.We employed near-infrared(NIR)light-responsive CRISPR/Cas9 plasmids delivery via a charge-reversal nanovector to achieve highly efficient and site-specific gene editing.The nanovector with abundant positive charges was fabricated on the basis of an ultraviolet-sensitive conjugated polyelectrolyte coated on an upconversion nanomaterial(UCNP-UVP-P),which can convert into negative charges upon 980 nm light irradiation.Using the as-prepared nanovector,we demonstrated the plasmids could be efficiency transfected into tumor cells(~63%±4%)in a time-contolled manner,and that functional CRISPR/Cas9 proteins could be successfully expressed in a selected NIR-irradiated region.Particularly,this strategy was successfully applied to the delivery of CRISPR/Cas9 gene to tumor cells in vivo,inducing high efficiency editing of the target gene PLK-1 under photolrradiation.Therefore,this precisely controlled gene regulation strategy has the potential to serve as a new paradigm for gene engineering in complex biological systems.