Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

Over the past few decades, humankind has constantly encountered new viral species that create havoc in the socioeconomic balance worldwide. Among the method to combat these novel viral infections, fast and point-of-care diagnosis is of prime importance to contain the spreading of viral infections. However, most sensitive diagnostic systems for viral infections are time-consuming and require well-trained professionals, making it difficult for the patients. In recent years nanozymes emerged as promising therapeutic and fast diagnostic tools due to their multienzyme-like catalytic performance. Nanozymes can be designed using inorganic or organic components with tailorable physicochemical surface properties, enabling the attachment of various molecules and species on the surface of the nanozyme for specific recognition. In addition to the composition, the multienzyme-like catalytic performance can be modulated by the shape and size of the nanoparticles. Due to their multicatalytic abilities, nanozymes can be used for fast diagnosis and therapy for viral infections. Here we attempt to focus on the insights and recent explorations on the advances in designing various types of nanozymes as a theranostic tool for viral infections. Thus, this review intends to generate interest in the clinical translation of nanozymes as a theranostic tool for viral infections by providing knowledge about the multidisciplinary potential of nanozyme. SIGNIFICANCE STATEMENT: The multienzyme-like properties of nanozymes suggest their role in diagnosing and treating various diseases. Although the potential roles of nanozymes for various viral infections have been studied in the last few decades, no review provides recent explorations on designing various types of nanozymes for the detection and treatment of viral infections. This review provides insights into designing nanozymes to diagnose and treat viral infections, assisting future researchers in developing clinically translatable nanozymes to combat novel viral infections.

ABSTRACT This investigation aims to develop a stimuli‐responsive nanocarrier to enhance the therapeutic efficiency of siRNA. Poly(ethylene imine) (PEI) and 3‐[(4‐Methylphenyl)thio]propionic acid (MPPA) were used to develop ion pair self‐assembly (IPSAM). This ion pair exhibited an upper critical solution temperature (UCST) behavior, and the UCST decreased when the H 2 O 2 concentration increased. The FT‐IR spectrum and 1 H‐NMR were studied in this study to verify the interaction between PEI and MPPA. IPSAM was found to be circular in TEM images, and the zeta potential of all IPSAM ratios showed positive results because IPSAM was likely affected by PEI. Therefore, the negatively charged siRNA can be loaded into IPSAM through the electrostatic interaction. At a temperature above UCST, IPSAM could be disassembled and release siRNA. In the oxidation, the sulfide bond of MPPA could be oxidized by H 2 O 2 to sulfone and sulfoxide. The UCST of the ion pair decreased, and IPSAM broke down, resulting in the promoted release. Pt nanoparticles were synthesized using the in situ method and contained in IPSAM. Under NIR irradiation, IPSAM can release the payloads due to heat generation and disassemble IPSAM. Moreover, siRNA loaded into IPSAM exhibited excellent cellular uptake and low cytotoxicity to C2C12 cells in vitro.

Immune cells show enormous potential for targeted nanoparticle delivery due to their intrinsic tumor-homing skills. However, the immune cells can internalize the nanoparticles, leading to cellular functional impairments, degradation of the nanoparticles, and delayed release of drugs from the immune cells. To address these issues, this study introduces an approach for the synthesis of freshly derived neutrophils (NUs)-based nanocarriers system where the NUs are surfaced by dialdehyde alginate-coated self-assembled micelles loaded with mitoxantrone (MIT) and indocyanine green (ICG) (i.e., dA(MI@IPM)s) for stimuli-responsive tumor-targeted therapy. Here, the dA(MI@IPM)s are not internalized by the NUs, but they are anchored on the membrane of the NUs via distearoylphosphatidylethanolamine-polyethylene glycol-polyethylenimine anchors. Owing to the natural recruitment ability of NUs to the tumor microenvironment, NUs-anchored dA(MI@IPM)s accumulation is higher at the tumor site than free dA(MI@IPM)s, where the dA(MI@IPM)s can readily detach from the NUs to get internalized in the tumor cells. The stimuli-responsive dA(MI@IPM)s disassembles inside the cancer cells upon near-infrared irradiation due to the photosensitizing effect of the loaded ICG, releasing MIT and significantly inhibiting tumor growth. This approach is simple and fast to prepare, opening up exciting possibilities for personalized cancer treatment using patient's autologous NUs.

Nonthermal plasma (NTP) has garnered attention for its potential in various biological activities. Due to the interactions with proteins and other cellular components, NTPs might stimulate osteoblast activity, but the exact mechanisms are still unknown. This study used two kinds of NTP: dielectric barrier discharge (DBD) and jet NTP (JNTP) to treat serum-free cell culture media at different time intervals. The indirect (plasma-media interfaces of ion exchange) exposure to osteoblasts was analyzed to determine whether it could influence osteoblast behavior and stimulate their osteogenic activity. Among various NTP-ionized media, 25% to 100% of the JNTP medium (JNTPM, treated for 10 min) showed noticeable induction of ALP activity in osteoblasts. 25% JNTPM induced maximum ALP activity and also demonstrated enhanced mRNA expression of osteogenic markers like Runx-2, Osterix, collagen 1α, bone sialoprotein, and osteocalcin. In addition, JNTPM treatment to osteoblasts demonstrated enhanced collagen production and mineralization. The administration of JNTPM to SaOS-2 cells increased Axin-2 reporter activity, along with enhanced stabilization of β-catenin and phosphorylation of GSK3-β, indicating the stimulation of the WNT signaling pathway. Moreover, JNTPM treatment increased osteoblasts' intracellular reactive oxygen species (ROS) levels. Prior exposure of N-acetyl-l-cysteine (NAC) to JNTPM-treated osteoblasts diminished the phosphorylation of GSK3-β, Axin-2 reporter activity, and the stability of β-catenin, highlighting the importance of intracellular ROS in enhancing Wnt signaling and osteogenic activity in osteoblasts in response to JNTPM. Thus, JNTPM treatment induces osteogenic stimulatory properties in osteoblasts through cross-talk between ROS and the Wnt signaling axis, suggesting a potential therapeutic approach for bone formation.

Microneedles have emerged as an effective strategy to bypass the stratum corneum by creating microchannels in the skin, allowing for enhanced drug permeation with minimal invasiveness. Pectin, a natural polysaccharide, when modified with thiol (-SH) groups, exhibits redox-sensitive behavior, making it responsive to reducing agents such as glutathione and dithiothreitol (DTT). The objective of this study was to investigate the transdermal delivery efficacy of redox-responsive microneedle-containing thiolated pectin. Various molar ratios of thiolated pectin were synthesized through the ring-opening reaction followed by nucleophilic substitution of propylene sulfide with pectin. MN matrices were formulated with thiolated pectin at various molar ratios, hyaluronic acid, collagen, and trehalose. The stiffness and mechanical strength of the microneedles increased with higher thiol-containing pectin molecules. The in vitro skin permeation release showed a large amount of FITC release when no thiol group was conjugated to pectin. MN-thio: pectin (20:10) with H₂O₂ showed greater release at higher DTT concentrations, and in the absence of DTT, the release was 50 times less than without thiol. In summary, the redox-responsive microneedle containing thiolated pectin may be a promising vehicle for transdermal drug delivery by harvesting the reducing agents in the human body.

Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.