Hyaluronic Acid-Based CuS Nanoenzyme Biodegradable Microneedles for Treating Deep Cutaneous Fungal Infection without Drug Resistance

Abstract

Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethyl­cellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.

Construction of Multi-Mode Photoelectrochemical Immunoassays for Accurate Detection of Cancer Markers: Assisted with MOF-Confined Plasmonic Nanozyme

“…Moreover, the Arduino microcontroller-based sensors could circumvent big RGB differences and large detection errors derived from the differences in camera algorithms from different mobile phone companies. As CuS is an excellent peroxidase-like nanozyme, , the integrated TiO 2 /ZIF-8/CuS could catalyze the TMB-H 2 O 2 and finally result in the change of color. First, from the results shown in Figure S14, the optimized detection pH was set at 4.…”

Photothermal and Acid-Responsive Fucoidan-CuS Bubble Pump Microneedles for Combined CDT/PTT/CT Treatment of Melanoma

“…Then, PBS (3150 μL, pH 8.0) solution and DTNB (100 mmol/L in DMSO, 10 μL) were added to the supernatant. The absorbance of the mixture was measured at 410 nm at different time points (5,10,20,30, and 60 min) by UV−vis spectroscopy.…”

“…9 Microneedles (MNs) with tip sizes ranging from 100 to 1000 μm can directly penetrate the stratum corneum to create micropores for drug delivery, providing a noninvasive, painless, and highly effective TDDS. 10 Particularly, stimuli-responsive MNs can enhance the effectiveness of transdermal therapy while minimizing the side effects related to off-target drug delivery, 5,11 which can release drugs in response to various physiological and physical signals. These signals can be internal, such as pH, 12 redox potential, 13 glucose levels, 14 and enzyme activity; 15 or external, including temperature, 16 electric field, 17 light, 18 and mechanical stress.…”

“…10.1021/acsami.3c08368. BPMNs quickly dissolved within 400 ms with clearly visible gas bubbles (MP4) Experimental details of more materials; characterization of Fuc-CuS NPs and BPMN-CuS/DOX; photothermal effect and biosafety in vivo; ROS generation and GSH depletion by the Fuc-CuS NPs; release profile of Cu ion from Fuc-CuS NPs; GSH depletion at cellular level; temperature curves of Fuc-CuS NPs under laser irradiation with the concentration of 800 μg/mL; cross-sectional fluorescence microscopy images BPMNs-FITC with 0, 10, and 25% of NaHCO 3 ; evaluation of the in vitro drug release performance of microneedles with different content of NaHCO 3 by fluorescence microscope; EDX profile of BPMN-CuS/ DOX; skin puncture marks at 0, 5, and 10 min by BPMN-CuS/DOX; IC 50 calculation of B16F10 cells after incubated with CuS at different concentrations (0, 12.5, 25, 50, 100, 200, 400, 800 μg/mL); live/dead cell staining assay; fluorescence intensity quantification of DCF; photothermal effects in vivo; and representative H&E staining images of major organs (PDF)…”

Multifunctional MXene-doped photothermal microneedles for drug-resistant bacteria-infected wound healing

“…Furthermore, multiple antibacterial active substances can be encapsulated inside the MN for treating bacterial infections. [18][19][20] However, traditional antibiotics pose a risk of inducing bacterial resistance like methicillin-resistant Staphylococcus aureus (MRSA) and even producing "super bacteria", which may cause side effects and damage the immune system. 21 Therefore, developing new antibacterial agents like nano-antibacterial materials and further constructing efficient combination strategies of MNs to improve antibacterial applications remain challenging.…”