Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.

Biomaterials-assisted cancer vaccine delivery: preclinical landscape, challenges, and opportunities.

INTRODUCTION: Cancer vaccines (protein and peptide, DNA, mRNA, and tumor cell) have achieved remarkable success in the treatment of cancer. In particular, advances in the design and manufacture of biomaterials have made it possible to control the presentation and delivery of vaccine components to immune cells. AREAS COVERED: This review summarizes findings from major databases, including PubMed, Scopus, and Web of Science, focusing on articles published between 2005 and 2024 that discuss biomaterials in cancer vaccine delivery. EXPERT OPINION: The development of cancer vaccines is hindered by several bottlenecks, including low immunogenicity, instability of vaccine components, and challenges in evaluating their clinical efficacy. To transform preclinical successes into viable treatments, it is essential to pursue continued innovation, collaborative research, and address issues related to scalability, regulatory pathways, and clinical validation, ultimately improving outcomes against cancer.

Antibacterial Agents and Adjuvants against Pseudomonas Aeruginosa Infections.

The development of narrow-spectrum antimicrobial agents is paramount for swiftly eradicating pathogenic bacteria, mitigating the onset of drug resistance, and preserving the homeostasis of bacterial microbiota in tissues. Owing to the limited affinity between the hydrophobic lipid bilayer interior of bacterial cells and most hydrophilic, polar peptides, the construction of a distinctive class of four-armed host-defense peptides/peptidomimetics (HDPs) is proposed with enhanced specificity and membrane perturbation capability against Pseudomonas aeruginosa by incorporating imidazole groups. These groups demonstrate substantial affinity for unsaturated phospholipids, which are predominantly expressed in the cell membrane of P. aeruginosa, thereby enabling HDPs to exhibit narrow-spectrum activity against this bacterium. Computational simulations and experimental investigations have corroborated that the imidazole-rich, four-armed peptidomimetics exhibit notable selectivity toward bacteria over mammalian cells. Among them, 4H10, characterized by its abundant and densely distributed imidazole groups, exhibits impressive activity against various clinically isolated P. aeruginosa strains. Moreover, 4H10 has demonstrated potential as an antibiotic adjuvant, enhancing doxycycline accumulation and exerting effects on intracellular targets by efficiently disrupting bacterial cell membranes. Consequently, the hydrogel composed of 4H10 and doxycycline emerged as a promising topical agent, significantly diminishing the skin P. aeruginosa burden by 97.1% within 2 days while inducing minimal local and systemic toxicity.

Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate.

OBJECTIVE: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems. METHODS: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure. RESULTS: P4 SLNs achieved a deeper diffusion depth of 180 µm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 µm). The in vivo experiments demonstrated that P4 SLNs had a T1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T1/2 of 13.12 h. CONCLUSIONS: This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies.

Photodynamic therapy (PDT) is a temporally and spatially precisely controllable, noninvasive, and potentially highly efficient method of phototherapy. The three components of PDT primarily include photosensitizers, oxygen, and light. PDT employs specific wavelengths of light to active photosensitizers at the tumor site, generating reactive oxygen species that are fatal to tumor cells. Nevertheless, traditional photosensitizers have disadvantages such as poor water solubility, severe oxygen-dependency, and low targetability, and the light is difficult to penetrate the deep tumor tissue, which remains the toughest task in the application of PDT in the clinic. Here, we systematically summarize the development and the molecular mechanisms of photosensitizers, and the challenges of PDT in tumor management, highlighting the advantages of nanocarriers-based PDT against cancer. The development of third generation photosensitizers has opened up new horizons in PDT, and the cooperation between nanocarriers and PDT has attained satisfactory achievements. Finally, the clinical studies of PDT are discussed. Overall, we present an overview and our perspective of PDT in the field of tumor management, and we believe this work will provide a new insight into tumor-based PDT.

Looking back, moving forward: protein corona of lipid nanoparticles.

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles.

Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate. Among various types of microneedles, nanoparticle-loaded dissolving microneedles (DMNs) present a unique combination of advantages, leveraging the strengths of DMNs (high payload, good mechanical properties, and easy fabrication) and nanocarriers (satisfactory solubilization capacity and a controlled release profile). Consequently, they hold considerable clinical application potential in the precision medicine era. Despite this promise, no nanoparticle-loaded DMN products have been approved thus far. The lack of understanding regarding their in vivo fate represents a critical bottleneck impeding the clinical translation of relevant products. This review aims to elucidate the current research status of the in vivo fate of nanoparticle-loaded DMNs and elaborate the necessity to investigate the in vivo fate of nanoparticle-loaded DMNs from diverse aspects. Furthermore, it offers insights into potential entry points for research into the in vivo fate of nanoparticle-loaded DMNs, aiming to foster further advancements in this field.

ATP-adenosine axis regulation combined with microneedle assisted photoimmunotherapy to boost the immunotherapy efficiency.

Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy.

Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer.

Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T2) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T2 relaxivity value 5.5 times higher than that of Resovist®. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.

Microneedle-assisted vaccination combined with autophagy regulation for antitumor immunotherapy.

Despite vaccination having the potency to revolutionize disease treatments, some critical issues including lack of safe and effective delivery system, insufficient internalization and ineffective antigen cross-presentation by dendritic cells (DCs) severely hamper its extensive clinical applications. Herein, we developed a whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs) potentiated with transdermal co-delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) and autophagy promoter (Tat-beclin 1). After transdermal vaccination with TCV-DMNs, GM-CSF released from DMNs serves as a potent adjuvant to recruit and promote the phagocytosis of antigens by DCs. Subsequently, Tat-beclin 1 promoted DCs maturation and MHC-I-mediated cross-presentation via up-regulated autophagy of DCs. We found that vaccination with TCV-DMNs could not only effectively suppress melanoma challenge, but also lead to regression of established malignancies, followed by a relapse-free survival of >40 days. Collectively, whole cell-encapsulated microneedle-assisted transdermal vaccination TCV-DMNs in combination with autophagy regulation could induce a robust antitumor immune response via enhancing transdermal delivery efficiency, promoting antigen internalization and cross-presentation, together with boosting T cell activities.

Demonstrating Biological Fate of Nanoparticle-Loaded Dissolving Microneedles with Aggregation-Caused Quenching Probes: Influence of Application Sites.

Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs. The aggregation-caused quenching (ACQ) probes P4 emitted intense fluorescence signals in intact NC while quenched after the degradation of NC, had been demonstrated the feasibility of label intact NC. In this study, P4 was loaded in solid lipid nanoparticles (SLNs), and further encapsulated into DMNs, to track the transdermal diffusion of SLNs delivered at different skin sites. The results showed that SLNs had excellent stability after being loaded into DMNs with no significant changes in morphology and fluorescence properties. The in vivo live and ex vivo imaging showed that the transdermal diffusion rate of NC-loaded DMNs was positively correlated with skin thickness, with the order ear > abdomen > back. In conclusion, this study confirmed the site-dependency of transdermal diffusion in NC-loaded DMNs.

A spark to the powder keg: Microneedle-based antitumor nanomedicine targeting reactive oxygen species accumulation for chemodynamic/photothermal/chemotherapy.

HYPOTHESIS: Chemodynamic therapy (CDT) can efficiently kill cancer cells by producing hydroxyl radical (•OH), a kind of high-toxic reactive oxygen species (ROS), via Fenton or Fenton-like reactions. This study involved a versatile nanomedicine, MSN@DOX/GA-Fe/PDA (M@DGP), delivered via microneedles, which was expected to combine chemodynamic/photothermal/chemotherapy and efficiently increase ROS accumulation to achieve significant therapeutic efficacy against melanoma. EXPERIMENTS: The composition of the synthesized nanoparticles was confirmed by a series of characterizations including transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential. The photothermal properties of the nanomedicine was evaluated via infrared imaging, and •OH-producing ability was evaluated by UV-Vis and electron spin resonance. The mechanisms of ROS accumulation were studied in B16 cells by detecting intracellular •OH, glutathione, and ROS levels. The drug-loaded microneedles (M@DGP-MNs) were prepared, and their morphology and mechanical strength were characterized. The in vivo antimelanoma effect and biosafety evaluation of the nanomedicine were investigated in tumor-bearing C57 mice. FINDINGS: M@DGP was successfully prepared and could achieve ROS accumulation through a photothermal-enhanced Fenton reaction, polydopamine-induced glutathione consumption, and doxorubicin-mediated mitochondrial dysfunction which induced oxidative stress and apoptosis of tumor cells. M@DGP-MNs showed superior antitumor efficacy and good biosafety, providing a promising strategy for melanoma treatment.

"Pincer movement": Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles.

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of "pincer movement" based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.

Guanidinium-rich lipopeptide functionalized bacteria-absorbing sponge as an effective trap-and-kill system for the elimination of focal bacterial infection.

Focal bacterial infections are often difficult to treat due to the rapid emergence of antibiotic-resistant bacteria, high risk of relapse, and severe inflammation at local lesions. To address multidrug-resistant skin and soft tissue infections, a bacteria-absorbing sponge was prepared to involve a "trap-and-kill" mechanism. The system describes a guanidinium-rich lipopeptide functionalized lyotropic liquid-crystalline hydrogel with bicontinuous cubic networks. Amphiphilic lipopeptides can be spontaneously anchored to the lipid-water interface, exposing their bacterial targeting sequences to enhance antibacterial trapping/killing activity. Computational simulations supported our structural predictions, and the sponge was confirmed to successfully remove ∼98.8% of the bacteria in the medium. Release and degradation behavior studies indicated that the bacteria-absorbing sponge could degrade, mediate enzyme-responsive lipopeptide release, or generate ∼200 nm lipopeptide nanoparticles with environmental erosion. This implies that the sponge can effectively capture and isolate high concentrations of bacteria at the infected site and then sustainably release antimicrobial lipopeptides into deep tissues for the eradication of residual bacteria. In the animal experiment, we found that the antibacterial performance of the bacterial-absorbing sponge was significant, which demonstrated not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also a unique advantage to protect tissue from bacterial attack. STATEMENT OF SIGNIFICANCE: Host defense peptides/peptidomimetics (HDPs) have shown potential for the elimination of focal bacterial infections, but the application of their topical formulations suffers from time-consuming preparation processes, indistinctive toxicity reduction effects, and inefficient bacterial capture ability. To explore new avenues for the development of easily prepared, low-toxicity and high-efficiency topical antimicrobials, a guanidinium-rich lipopeptide was encapsulated in a lyotropic liquid-crystalline hydrogel (denoted as "bacteria-absorbing sponge") to achieve complementary superiorities. The superior characteristic of the bacteria-absorbing sponge involves a "trap-and-kill" mechanism, which undergoes not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also effective bacterial capture and isolating action to confine bacterial diffusion and protect tissues from bacterial attack.

A Perfect Pair: Stabilized Black Phosphorous Nanosheets Engineering with Antimicrobial Peptides for Robust Multidrug Resistant Bacteria Eradication.

Black phosphorus (BP) nanosheets emerged as promising 2D nanomaterial that have been applied to eradicate antibiotic-resistant bacteria. However, their applications are limited by intrinsic ambient instability. Here, the ε-poly-l-lysine (ε-PL)-engineered BP nanosheets are constructed via simple electrostatic interaction to cater the demand for passivating BP with amplified antibacterial activity. The dual drug-delivery complex named BP@ε-PL can closely anchor onto the surface of bacteria, leading to membrane disintegration. Subsequently, in situ hyperthermia generated by BP under near-infrared (NIR) irradiation can precisely eradicate pathogenic bacteria. In vitro antibacterial studies verify the rapid disinfection ability of BP@ε-PL against Methicillin-resistant Staphylococcus aureus (MRSA) within 15 min. Moreover, ε-PL can serve as an effective protector to avoid chemical degradation of bare BP. The in vivo antibacterial study shows that a 99.4% antibacterial rate in a MRSA skin infection model is achieved, which is accompanied by negligible toxicity. In conclusion, this work not merely provides a new conjecture for protecting the BP, but also opens a novel window for synergistic antibiotic-resistant bacteria therapy based on antimicrobial peptides and 2D photothermal nanomaterial.

Inhalable cryptotanshinone spray-dried swellable microparticles for pulmonary fibrosis therapy by regulating TGF-ß1/Smad3, STAT3 and SIRT3 pathways.

Cryptotanshinone (CTS) is a promising therapeutic option for pulmonary fibrosis (PF). However, clinical applications of CTS are limited owing to high photosensitivity and poor oral bioavailability. Pulmonary drug delivery, especially sustained pulmonary drug delivery, is promising for local treatment of chronic lung diseases. In this study, CTS was encapsulated in an optimized chitosan/L-leucine-based swellable microparticles (SMs) system, which exhibited an appropriate aerosolization performance, sustained release and storage stability. SMs enhanced the in vitro anti-fibrosis efficacy of CTS as shown by the improved cellular uptake. The effect of PF status on in vivo fate of the pulmonary delivered drug was also assessed. Pharmacokinetics and tissue distribution of oral and pulmonary delivery CTS in bleomycin-induced PF rats were compared. Pulmonary delivery exhibited high drug concentrations in pulmonary lesion areas, with reduced exposure to blood and non-targeted tissues after administration at a significantly lower dose compared with oral delivery. Moreover, PF pathological status enhanced activity of SMs, implying that pulmonary delivery was highly effective for PF treatment. Compared to oral delivery, Inhaled SMs showed comparable or even better efficacies at approximately 60-fold low dose compared with oral delivery. A sustained efficacy was observed under a prolonged administration interval (corresponding to half the total dose). Inhalation safety of SMs was established, and important mechanism-related signaling pathways against PF were investigated in vitro and in vivo. In summary, the findings showed that the developed CTS-loaded sustained pulmonary delivery system is a safe and effective strategy for chronic PF treatment.

Titanium carbide MXene-based hybrid hydrogel for chemo-photothermal combinational treatment of localized bacterial infection.

With the increased emergence and threat of multi-drug resistant microorganisms, MXenes have become not only an emerging class of two-dimensional functional nanomaterials, but also potential nanomedicines (i.e., antimicrobial agents) that deserve further exploration. Very recently, Ti3C2 MXene was observed to offer a unique membrane-disruption effect and superior light-to-heat conversion efficiency, but its antibacterial property remains unsatisfactory due to poor MXene-bacteria interactions, low photothermal therapy efficiency, and occurrence of bacterial rebound in vivo. Herein, the cationic antibiotic ciprofloxacin (Cip) is combined with Ti3C2 MXene, and a hybrid hydrogel was constructed by incorporating Cip-Ti3C2 nanocomposites into the network structure of a Cip-loaded hydrogels to effectively trap and kill bacteria. We found that the Cip-Ti3C2 nanocomposites achieved an impressive in vitro bactericidal efficiency of >99.99999% (7.03 log10) for the inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by combining chemotherapy with photothermal therapy. In an MRSA-induced murine abscess model, the hybrid hydrogel simultaneously achieved high-efficiency sterilization and long-term inhibition effects, avoiding the rebound of bacteria after photothermal therapy, and thus maximized the in vivo therapeutic efficacy of Ti3C2 MXene-based systems. Overall, this work provides a strategy for efficiently combating localized bacterial infection by rationally designing MXene-based hybrid hydrogels. STATEMENT OF SIGNIFICANCE: Two-dimensional Ti3C2 MXene was recently regarded as a promising functional nanomaterial, however, its antibacterial applications are limited by the poor MXene-bacteria interactions, low photothermal therapy efficiency, and the occurrence of bacterial rebound in vivo. This work aims to construct a Ti3C2 MXene-based hybrid hydrogel for chemo-photothermal therapy and enhance the antimicrobial performance via a combination of the high-efficiency sterilization of ciprofloxacin-Ti3C2 nanocomposites with the long-term inhibition effect of ciprofloxacin hydrogel. The present study provides an example of efficient MXene-based antimicrobials to treat localized bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA)-induced skin abscess.

Cellular defense system-destroying nanoparticles as a platform for enhanced chemotherapy against drug-resistant cancer.

Cellular defense system represented by glutathione (GSH) greatly weakens the outcomes of cancer therapy by antioxidation and detoxification. GSH depletion has been proved to be an effective way to enhance the efficacy of reactive oxygen species (ROS)-based therapies and chemotherapy. However, the existing strategies of GSH depletion still face the problems of unclear biosafety and high complexity of multicomponent co-delivery. In this study, we developed a GSH-depleting carrier platform based on disulfide-bridged mesoporous organosilica nanoparticles (MONs) to destroy the cellular defense system for cancer therapy. Responding to the high level of GSH in cancer cells, the disulfide bonds in the framework of MONs could be broken and consumed substantial GSH at the same time. Moreover, this process also promoted the degradation of MONs. In order to evaluate the effect of this platform in cancer therapy, chemotherapeutic drug cisplatin was loaded into MONs (Pt@MONs) to treat drug-resistant non-small cell lung cancer. In vitro and in vivo results indicated that Pt@MONs efficiently triggered GSH depletion, promoted platinum-DNA adduct formation, and induced cell apoptosis, resulting in significant tumor growth inhibition without marked toxicity. Taken together, the cellular defense system-destroying nanoparticles provide a promising platform for enhanced cancer therapy.

Correction: Microneedle-mediated delivery of MIL-100(Fe) as a tumor microenvironment-responsive biodegradable nanoplatform for O2-evolving chemophototherapy.

Correction for 'Microneedle-mediated delivery of MIL-100(Fe) as a tumor microenvironment-responsive biodegradable nanoplatform for O2-evolving chemophototherapy' by Sulan Luo et al., Biomater. Sci., 2021, DOI: 10.1039/d1bm00888a.