[Application of two noninvasive scores in predicting the risk of respiratory failure in full-term neonates: a comparative analysis]. / ä¸¤ç§æ— åˆ›è¯„åˆ†æ³•åœ¨è¶³æœˆæ–°ç”Ÿå„¿å‘¼å¸è¡°ç«­é£Žé™©é¢„æµ‹ä¸­çš„åº”ç”¨æ¯”è¾ƒ.

OBJECTIVES: To study the value of Silverman-Anderson score versus Downes score in predicting respiratory failure in full-term neonates. METHODS: The convenience sampling method was used to select the full-term neonates with lung diseases who were hospitalized in the neonatal intensive care unit from July 2020 to July 2021. According to the diagnostic criteria for neonatal respiratory failure, they were divided into a respiratory failure group (65 neonates) and a non-respiratory failure group (363 neonates). Silverman-Anderson score and Downes score were used for evaluation. The receiver operating characteristic analysis was used to compare the value of the two noninvasive scores in predicting respiratory failure in full-term neonates. RESULTS: Among the 428 full-term neonates, 65 (15.2%) had respiratory failure. The Silverman-Anderson score had a significantly shorter average time spent on evaluation than the Downes score [(90±8) seconds vs (150±13) seconds; P<0.001]. The respiratory failure group had significantly higher points in both the Silverman-Anderson and Downes scores than the non-respiratory failure group (P<0.001). The Silverman-Anderson score had an AUC of 0.876 for predicting respiratory failure, with a sensitivity of 0.908, a specificity of 0.694, and a Youden index of 0.602 at the optimal cut-off value of 4.50 points. The Downes score had an AUC of 0.918 for predicting respiratory failure, with a sensitivity of 0.723, a specificity of 0.953, and a Youden index of 0.676 at the optimal cut-off value of 6.00 points. The Downes score had significantly higher AUC for predicting respiratory failure than the Silverman-Anderson score (P=0.026). CONCLUSIONS: Both Silverman-Anderson and Downes scores can predict the risk of respiratory failure in full-term neonates. The Silverman-Anderson score requires a shorter time for evaluation, while the Downes score has higher prediction efficiency. It is recommended to use Downes score with higher prediction efficiency in general evaluation, and the Silverman-Anderson score requiring a shorter time for evaluation can be used in emergency.

Versatile Nanoscale Metal-Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications.

For decades, nanoscale metal-organic frameworks (nMOFs) have attracted extensive interest in biomedicine due to their distinct characteristics, including facile synthesis, porous interior, and tunable biocompatibility. With high porosity, versatile nMOFs allow for the facile encapsulation of various therapeutic agents with exceptionally high payloads. Constructed from metal ions and organic linkers through coordination bonds, nMOFs with plentiful functional groups enable the surface modification for active targeting and enhanced biocompatibility. This review outlines the up-to-date progresses on the exploration of nMOFs in the field of biomedicine. First, the classification and synthesis of nMOFs are discussed, followed by the concrete introduction of drug loading strategies of nMOFs and mechanisms of stimulation-responsive drug release. Second, the smart designs of the nMOFs-based platforms for anticancer and antibacterial treatment are summarized. Finally, the basic challenges faced by nMOFs research and the great potential of biomimetic nMOFs are presented. This review article affords an inspiring insight into the interdisciplinary research of nMOFs and their biomedical applications, which holds great expectation for their further clinical translation.

"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.

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.

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.

The rough inhalable ciprofloxacin hydrochloride microparticles based on silk fibroin for non-cystic fibrosis bronchiectasis therapy with good biocompatibility.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease, and the thick and viscous mucus covering on respiratory epithelia can entrap the inhaled drugs, resulting in compromised therapeutic efficiency. In order to solve this problem, the inhalable ciprofloxacin hydrochloride microparticles (CMs) based on silk fibroin (SF) and mannitol (MAN) were designed and developed. SF was applied to increase the loading efficiency of ciprofloxacin hydrochloride by strong electrostatic interactions. MAN could facilitate the penetration of drugs through mucus, which ensured the drugs could reach their targets before clearance. Furthermore, the aerodynamic performance of the inhalable microparticles could be tuned by changing the surface roughness to achieve a high fine particle fraction value (45.04%). The antibacterial effects of CMs were also confirmed by measuring the minimum inhibitory concentration against four different bacteria strains. Moreover, a series of experiments both in vitro and in vivo showed that CMs would not affect the lung function and induce the secretion of inflammatory cytokines in lungs, demonstrating their excellent biocompatibility and biosafety. Therefore, CMs might be a promising pulmonary drug delivery system for the treatment of NCFB.

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.

Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy.

Glutathione (GSH) is an important member of cellular antioxidative system. In cancer cells, a high level of GSH is indispensable to scavenge excessive reactive oxygen species (ROS) and detoxify xenobiotics, which make it a potential target for cancer therapy. Plenty of studies have shown that loss of intracellular GSH makes cancer cells more susceptible to oxidative stress and chemotherapeutic agents. GSH depletion has been proved to improve the therapeutic efficacy of ROS-based therapy (photodynamic therapy, sonodynamic therapy, and chemodynamic therapy), ferroptosis, and chemotherapy. In this review, various strategies for GSH depletion used in cancer therapy are comprehensively summarized and discussed. First, the functions of GSH in cancer cells are analyzed to elucidate the necessity of GSH depletion in cancer therapy. Then, the synthesis and metabolism of GSH are briefly introduced to bring up some crucial targets for GSH modulation. Finally, different approaches to GSH depletion in the literature are classified and discussed in detail according to their mechanisms. Particularly, functional materials with GSH-consuming ability based on nanotechnology are elaborated due to their unique advantages and potentials. This review presents the ingenious application of GSH-depleting strategy in cancer therapy for improving the outcomes of various therapeutic regimens, which may provide useful guidance for designing intelligent drug delivery system.

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.

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

The low oxygen level in tumors significantly reduces the antitumor efficacy of photodynamic therapy (PDT). The provision of O2 and monomeric hydrophobic photosensitizers (PSs) under physiological conditions would greatly help to shrink malignant tumors. We take advantage of the high porosity and multifunctionality of metal-organic frameworks (MOFs) to fabricate a simple all-in-one nanoplatform mediated by microneedle delivery to achieve synergistic O2 evolution and chemophototherapy. An iron(III)-based MOF (MIL-100(Fe)) acted not only as a vehicle for the concurrent delivery of zinc phthalocyanine (ZnPc) and doxorubicin hydrochloride (Dox), but also to supply O2 by decomposing hydrogen peroxide (H2O2) in the tumor microenvironment via a Fenton-like reaction. In vitro and in vivo experiments indicated that the nanoplatform had excellent biocompatibility and exerted enhanced anticancer effects. The encapsulated drug was sustainably released from the nanoplatform skeleton in response to acidic tumor microenvironments. Moreover, upon 660 nm light irradiation, ZnPc effectively produced reactive oxygen species (ROS) due to the reduction of hypoxia by MIL-100(Fe). A microneedle technique was adopted to directly deliver the nanoplatform into superficial tumors rather than via systemic circulation. Hence, this study provides a new strategy for more efficient chemophototherapy of hypoxic superficial tumors.

Multifunctional nanoreactors-integrated microneedles for cascade reaction-enhanced cancer therapy.

Starvation therapy based on glucose oxidase (GOx) has attracted considerable attention in tumor treatment. However, several shortcomings severely hinder its further applications, including limited therapeutic efficacy, poor enzyme stability, and potential side effects. Herein, a strategy of cascade reaction-enhanced combined therapy based on the oxygen-evolving multifunctional nanoreactors is proposed for tumor therapy. The GOx and catalase (CAT) are immobilized in metal-organic frameworks by biomimetic mineralization to improve their stability via spatial confinement. The GOx can consume glucose, reduce ATP levels, and down-regulate the expression of heat shock proteins, which consequently sensitize tumor cells to indocyanine green-based photothermal therapy. Furthermore, the hydrogen peroxide generated by GOx as well as overexpressed in tumor can be decomposed by CAT and continuously generate oxygen, which further enhance the efficacy of oxygen-dependent starvation therapy and photodynamic therapy. The nanoreactors are directly delivered to the superficial tumor by microneedles, achieving efficient tumor accumulation and dramatically strengthened antitumor efficacy without obvious side effects, which provides a valuable paradigm for the application of cascade reaction-based combined therapy.

Intelligent and spatiotemporal drug release based on multifunctional nanoparticle-integrated dissolving microneedle system for synergetic chemo-photothermal therapy to eradicate melanoma.

Cutaneous melanoma is one of the most common malignant skin cancer with high lethality. Chemotherapy and photothermal therapy are important and extensively studied treatment modalities for melanoma. However, these therapies still face some challenges, which severely restrict their further applications, such as unsatisfactory efficacy of monotherapy, nonspecific uptake and release during drug delivery, and unexpected adverse effects from system administration. Recently, the strategies of collaboration, functional modification, stimuli-responsive design, and topical administration all show great prospect for solving above problems. In this research, a multifunctional nanoparticle-integrated dissolving microneedle drug delivery system was constructed, in which the nanoparticles were prepared based on the framework with the incorporation of photothermal agent (CuS) into Zeolitic imidazolate framework-8 and functionalized by hyaluronic acid. This system can co-load multi-modal drugs, improve specific uptake and distribution of targeted tumor, deliver drug locally, and release drug intelligently and spatiotemporally, thereby promising a low-dose administration with high efficiency. The high inhibiting tumor performance and excellent systematic safety were verified both in vitro and in vivo. Together, this smart design overcame the drawbacks of monotherapy and conventional system administration. We believe the nanoparticle-integrated dissolving microneedles will be in prospect of clinical application for more superficial tumors with further delicate optimization. STATEMENT OF SIGNIFICANCE: Melanoma is one of the most common skin cancers with high lethality. Extensively studied chemotherapy and photothermal therapy still face some challenges, such as the limited therapeutic efficacy and the severe system adverse effects. In order to overcome these drawbacks, the multifunctional nanoparticle-integrated dissolving microneedles (DMNs) were designed. Especially, the nanoparticles could co-load multi-modal drugs, improve specific uptake, and release drug intelligently and spatiotemporally. The microneedles could increase the drug accumulation in tumor, thus achieving excellent therapeutic efficacy and reducing side effects. This system paved the way to a less invasive, more focused and efficient therapeutic strategy for melanoma therapy.

Bioresponsive Nanoarchitectonics-Integrated Microneedles for Amplified Chemo-Photodynamic Therapy against Acne Vulgaris.

The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.

Cyclodextrin-based metal-organic frameworks for pulmonary delivery of curcumin with improved solubility and fine aerodynamic performance.

Pulmonary drug delivery has attracted considerable attention in recent years. However, it is still a major challenge to deliver poorly water-soluble drugs to lungs with good solubility and fine aerodynamic performance. In this study, curcumin was loaded into cyclodextrin-based metal-organic frameworks (CD-MOFs) for pulmonary delivery. Compared with micronized curcumin prepared by jet milling, curcumin-loaded CD-MOFs (Cur-CD-MOFs) exhibited excellent aerodynamic performance, which was attributed to the unique porous structure and lower density of CD-MOFs. The dissolution test showed that the drug release rate of Cur-CD-MOFs was much faster than that of micronized curcumin. The all-atom molecular dynamic simulation showed that curcumin molecules were loaded into the hydrophobic cavities of CD-MOFs or entered into the large hydrophilic cavities to form nanoclusters. The elevated wettability of Cur-CD-MOFs and the unique spatial distribution feature of curcumin in porous interior of CD-MOFs might be favorable for the improved dissolution rate. The DPPH radical scavenging test showed that Cur-CD-MOFs had prominent antioxidant activities. Therefore, CD-MOFs were expected to be promising carriers for pulmonary delivery of poorly water-soluble drugs.

A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility.

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation, in vivo lung injury markers measurement, and histological analysis. The results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in lungs. Therefore, all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery. This study may throw light on the nanoporous particles for effective pulmonary administration.

Tailored core‒shell dual metal-organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy.

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles, with a significantly higher inhibition rate. It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.

Erratum: Wu, B.; et al. Metal-Organic Framework-Based Chemo-Photothermal Combinational System for Precise, Rapid, and Efficient Antibacterial Therapeutics. Pharmaceutics 2019, 11, 463.

The authors wish to make the following corrections to this paper [1]: the hematoxylin and eosin-stained images of kidney in the group of healthy tissue in Figure 8 of this work [1] inadvertently duplicated the kidney results of the PBS group.[...].

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism.

BACKGROUND: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. OBJECTIVE: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. METHODS: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. RESULTS: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). CONCLUSION: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

Metal-Organic Framework-Based Chemo-Photothermal Combinational System for Precise, Rapid, and Efficient Antibacterial Therapeutics.

Rapid increase of antimicrobial resistance has become an urgent threat to global public health. In this research, since photothermal therapy is a potential antibacterial strategy, which is less likely to cause resistance, a metal-organic framework-based chemo-photothermal combinational system was constructed. Zeolitic imidazolate frameworks-8 (ZIF-8), a porous carrier with unique features such as high loading and pH-sensitive degradation, was synthesized, and then encapsulated photothermal agent indocyanine green (ICG). First, ICG with improved stability in ZIF-8 (ZIF-8-ICG) can effectively produce heat in response to NIR laser irradiation for precise, rapid, and efficient photothermal bacterial ablation. Meanwhile, Zn2+ ions released from ZIF-8 can inhibit bacterial growth by increasing the permeability of bacterial cell membrane and further strengthen photothermal therapy efficacy by reducing the heat resistance of bacteria. Study showed that bacteria suffered from significant changes in morphology after treatment with ZIF-8-ICG under laser irradiation. The combinational chemo-hyperthermia therapy of ZIF-8-ICG could thoroughly ablate murine subcutaneous abscess induced by methicillin-resistant Staphylococcus aureus (MRSA), exhibiting a nearly 100% bactericidal ratio. Both in vitro and in vivo safety evaluation confirmed that ZIF-8-ICG was low toxic. Overall, our researches demonstrated that ZIF-8-ICG has great potential to be served as an alternative to antibiotics in combating multidrug-resistant bacterial pathogens.

Ultramild One-Step Encapsulating Method as a Modular Strategy for Protecting Humidity-Susceptible Metal-Organic Frameworks Achieving Tunable Drug Release Profiles.

Metal-organic frameworks (MOFs), composed of metal ions or clusters and organic ligands, have emerged as a new class of porous materials. However, water instability of many MOFs has impeded their further applications. Herein, an ultramild one-step encapsulating method has been developed by incorporating γ-cyclodextrin-based MOFs (CD-MOFs) into hydrophobic ethylcellulose to fabricate composite microparticles for ideal hydrolytic stability. The whole process can be completed at ambient temperature by the novel ultrafine particle processing system in several minutes without any purification or drying steps. The composite microparticles well retained their morphology and crystal structure of CD-MOFs even after being exposed to extreme humid environment for 30 d. The composite microparticles were further exploited for drug delivery. The composite microparticles not only exhibited sustained and tunable pH-dependent drug release profiles in simulated physiological conditions but also reduced cell toxicity compared with drug-loaded CD-MOFs, which demonstrated that the composite microparticles were promising as drug carriers. In summary, this study developed a modular strategy for protecting humidity-susceptible MOFs with controlled release profiles, which is expected to open up a new avenue to expand their applications in the biomedical field.