An antibacterial, multifunctional nanogel for efficient treatment of neutrophilic asthma.

Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro, suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.

Research progress on antibacterial applications of metal-organic frameworks and their biomacromolecule composites.

With the extensive use of antibiotics, resulting in increasingly serious problems of bacterial resistance, antimicrobial therapy has become a global concern. Metal-organic frameworks (MOFs) are low-density porous coordination materials composed of metal ions and organic ligands, which can form composite materials with biomacromolecules such as proteins and polysaccharides. In recent years, MOFs and their derivatives have been widely used in the antibacterial field as efficient antibacterial agents. This review offers a detailed summary of the antibacterial applications of MOFs and their composites, and the different synthesis methods and antibacterial mechanisms of MOFs and MOF-based composites are briefly introduced. Finally, the challenges and prospects of MOFs-based antibacterial materials in the rapidly developing medical field were briefly discussed. We hope this review will provide new strategies for the medical application of MOFs-based antibacterial materials.

Preparation of Budesonide-Loaded Liposomal Nanoparticles for Pulmonary Delivery and Their Therapeutic Effect in OVA-Induced Asthma in Mice.

Purpose: Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment. Methods: BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed. Results: The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD. Conclusion: BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.

Research progress of polyphenols in nanoformulations for antibacterial application.

Infectious disease is one of the top 10 causes of death worldwide, especially in low-income countries. The extensive use of antibiotics has led to an increase in antibiotic resistance, which poses a critical threat to human health globally. Natural products such as polyphenolic compounds and their derivatives have been shown the positive therapeutic effects in antibacterial therapy. However, the inherent physicochemical properties of polyphenolic compounds and their derivatives limit their pharmaceutical effects, such as short half-lives, chemical instability, low bioavailability, and poor water solubility. Nanoformulations have shown promising advantages in improving antibacterial activity by controlling the release of drugs and enhancing the bioavailability of polyphenols. In this review, we listed the classification and antibacterial mechanisms of the polyphenolic compounds. More importantly, the nanoformulations for the delivery of polyphenols as the antibacterial agent were summarized, including different types of nanoparticles (NPs) such as polymer-based NPs, metal-based NPs, lipid-based NPs, and nanoscaffolds such as nanogels, nanofibers, and nanoemulsions. At the same time, we also presented the potential biological applications of the nano-system to enhance the antibacterial ability of polyphenols, aiming to provide a new therapeutic perspective for the antibiotic-free treatment of infectious diseases.

Advances in preparation and application of antibacterial hydrogels.

Bacterial infections, especially those caused by drug-resistant bacteria, have seriously threatened human life and health. There is urgent to develop new antibacterial agents to reduce the problem of antibiotics. Biomedical materials with good antimicrobial properties have been widely used in antibacterial applications. Among them, hydrogels have become the focus of research in the field of biomedical materials due to their unique three-dimensional network structure, high hydrophilicity, and good biocompatibility. In this review, the latest research progresses about hydrogels in recent years were summarized, mainly including the preparation methods of hydrogels and their antibacterial applications. According to their different antibacterial mechanisms, several representative antibacterial hydrogels were introduced, such as antibiotics loaded hydrogels, antibiotic-free hydrogels including metal-based hydrogels, antibacterial peptide and antibacterial polymers, stimuli-responsive smart hydrogels, and light-mediated hydrogels. In addition, we also discussed the applications and challenges of antibacterial hydrogels in biomedicine, which are expected to provide new directions and ideas for the application of hydrogels in clinical antibacterial therapy.

PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases.

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are critical areas of medical research, as millions of people are affected worldwide. In fact, more than 9 million deaths worldwide were associated with respiratory diseases in 2016, equivalent to 15% of global deaths, and the prevalence is increasing every year as the population ages. Due to inadequate treatment options, the treatments for many respiratory diseases are limited to relieving symptoms rather than curing the disease. Therefore, new therapeutic strategies for respiratory diseases are urgently needed. Poly (lactic-co-glycolic acid) micro/nanoparticles (PLGA M/NPs) have good biocompatibility, biodegradability and unique physical and chemical properties, making them one of the most popular and effective drug delivery polymers. In this review, we summarized the synthesis and modification methods of PLGA M/NPs and their applications in the treatment of respiratory diseases (asthma, COPD, cystic fibrosis (CF), etc.) and also discussed the research progress and current research status of PLGA M/NPs in respiratory diseases. It was concluded that PLGA M/NPs are the promising drug delivery vehicles for the treatment of respiratory diseases due to their advantages of low toxicity, high bioavailability, high drug loading capacity, plasticity and modifiability. And at the end, we presented an outlook on future research directions, aiming to provide some new ideas for future research directions and hopefully to promote their widespread application in clinical treatment.

Optimized DOX Drug Deliveries via Chitosan-Mediated Nanoparticles and Stimuli Responses in Cancer Chemotherapy: A Review.

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan-DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy.

Recent Advances in Nanomaterials for Asthma Treatment.

Asthma is a chronic airway inflammatory disease with complex mechanisms, and these patients often encounter difficulties in their treatment course due to the heterogeneity of the disease. Currently, clinical treatments for asthma are mainly based on glucocorticoid-based combination drug therapy; however, glucocorticoid resistance and multiple side effects, as well as the occurrence of poor drug delivery, require the development of more promising treatments. Nanotechnology is an emerging technology that has been extensively researched in the medical field. Several studies have shown that drug delivery systems could significantly improve the targeting, reduce toxicity and improve the bioavailability of drugs. The use of multiple nanoparticle delivery strategies could improve the therapeutic efficacy of drugs compared to traditional delivery methods. Herein, the authors presented the mechanisms of asthma development and current therapeutic methods. Furthermore, the design and synthesis of different types of nanomaterials and micromaterials for asthma therapy are reviewed, including polymetric nanomaterials, solid lipid nanomaterials, cell membranes-based nanomaterials, and metal nanomaterials. Finally, the challenges and future perspectives of these nanomaterials are discussed to provide guidance for further research directions and hopefully promote the clinical application of nanotherapeutics in asthma treatment.

Biomineralized Two-Enzyme Nanoparticles Regulate Tumor Glycometabolism Inducing Tumor Cell Pyroptosis and Robust Antitumor Immunotherapy.

Currently, immune checkpoint therapy combined with chemotherapy and radiotherapy is a useful strategy for improving immunotherapy's therapeutic efficacy. However, chemotherapy and radiotherapy cause serious side effects, so finding safe and effective methods to combine with immunotherapy is critical. In this work, regulating tumor glycometabolism is found to induce tumor cell pyroptosis and regulate the degree of expression of programmed death-ligand 1 (PD-L1). Therefore, how to treat tumors by regulating tumor glycometabolism in combination with anti-PD-L1 therapy is investigated here. First, the biomineralization-like method is used to construct nanoparticles with two-enzymatic activity by hybridizing nanozymes and glucose oxidase (GOx). It has the ability to self-amplify regulation of the glycometabolism of tumor cells. It can also induce tumor cell pyroptosis and increase the expression of PD-L1 in tumor cells. To treat tumors, nanoparticles are further combined with anti-PD-L1, which substantially inhibits tumor development and significantly increases  the survival time of mice. Combination therapy also has a significant immunological memory effect, successfully preventing tumor recurrence and metastasis. This is thought to be the first study that combines tumor glycometabolism with immunocheckpoint blocking in cancer therapy. This innovative, safe, low-toxic, and highly effective anti-tumor strategy can have good prospects in clinical applications.

A generally minimalist strategy of constructing biomineralized high-efficiency personalized nanovaccine combined with immune checkpoint blockade for cancer immunotherapy.

As a representative of tumor immunotherapy, tumor vaccine can inhibit tumor growth by activating tumor-specific immune response, which has the advantages of relatively low toxicity and high efficiency, and has attracted much attention in recent years. However, there are still difficulties in how to effectively deliver tumor vaccines in vivo and make them work efficiently. It is a relatively mature method to load tumor specific antigens with suitable carriers to produce tumor vaccines. Here, a generally minimalist construction method of tumor nanovaccine was developed. A high-efficiency tumor nanovaccine (NV) was prepared in one step by a biomineralization-like method, which contained ovalbumin (OVA, model antigen), unmethylated cytosine-phosphate-guanine (CpG, adjuvant) and Mn-NP (carrier and adjuvant). NV not only showed good tumor preventive effect, but also could successfully inhibited tumor development and metastasis when combined with anti-PD-L1, and induced long-term immune memory effect. However, the method of screening tumor specific antigen to construct nanovaccine is cumbersome and tumors are heterogeneous. Therefore, surgically resected tumor tissue is the best source of antigens for preparing tumor vaccines. Next, based on the strong loading ability of the carrier, we designed a personalized tumor nanovaccine (PNV) using the supernatant of tumor abrasive fluid (STAF) as antigen based on the generally minimalist tumor nanovaccine construction strategy. PNV combined with anti-PD-L1 could successfully inhibit post-surgical tumor recurrence and induce strong and durable immune memory effects. This study presents a novel, general, and minimalist strategy to construct high-efficiency personalized nanovaccine, which has a wide range of potential applications in the field of tumor treatment.

Antibacterial activity of guanidinium-based ionic covalent organic framework anchoring Ag nanoparticles.

In this paper, the antibacterial 2D covalent organic framework (COFTGTp) containing guanidyl cation was synthesized and used as a carrier to deposit AgNPs on N and O groups to form nanocomposites to avoid AgNPs aggregation and achieve excellent antibacterial effect. The Ag content in Ag/COFTGTp was 10.3% determined by ICP. TEM can clearly observe that AgNPs were uniformly dispersed in COFTGTp. Ag/COFTGTp was stable after being evenly dispersed in water with low cytotoxicity and hemolysis rate to erythrocytes. In bacteriostatic study, the minimum inhibitory concentration of Ag/COFTGTp for E. coli and S. aureus were 100 µg/mL and 50 µg/mL, respectively. Finally, the morphology of the bacteria was observed by SEM, confirmed the main sterilization by Ag/COFTGTp was destroying the cell wall of the bacteria.

The Value of High-Resolution Ultrasound Combined with Shear-Wave Elastography under Artificial Intelligence Algorithm in Quantitative Evaluation of Skin Thickness in Localized Scleroderma.

The aim of this study was to explore the value of high-resolution ultrasound combined with shear-wave elastography (SWE) in measuring skin thickness in patients with localized scleroderma (LS). Fifty patients with LS diagnosed by pathology in the hospital were selected as the research object, with a total of 96 lesions. Healthy people (50 cases) in the same period were selected as the control group. The skin thickness of the abdomen, chest, and left finger of the two groups was compared. The traditional nonlocal means (NLM) algorithm was improved by changing the Euclidean distance and introducing a cosine function, which was applied to the ultrasonic imaging intelligent diagnosis of patients with localized scleroderma. SWE imaging was evaluated, and the results demonstrated that LS lesion edema stage accounted for 7.29%, hardening stage occupied 43.75%, and the proportion of atrophy stage reached 48.96%. When the size of shell was 1 mm, maximum elastic modulus (E max) was 0.984, mean of elastic modulus (Emean) was 0.926, and electro-static discharge (Esd) was 0.965. When the size of shell was 2 mm, the elastic moduli around lesions were as follows: Emax was 0.998, Emean was 0.968, and Esd was 0.997. By comparing the skin thickness of the abdomen, chest, and left finger, it was found that there was a significant difference between the LS group and the control group (P < 0.05). When the shell was 2 mm, the effect of sensitivity specificity on SWE imaging was better than that when the shell was 1 mm. In summary, the improved NLM algorithm showed excellent denoising effects on the ultrasonic images of LS patients. Besides, it could assist clinicians in ultrasonic imaging diagnosis for LS patients and effectively improve the diagnostic accuracy of diseases.

Metal-organic framework-mediated multifunctional nanoparticles for combined chemo-photothermal therapy and enhanced immunotherapy against colorectal cancer.

Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.

Ultrasonographic features of eccrine spiradenoma: A case report.

RATIONALE: Eccrine spiradenoma (ES) is a rare benign skin adnexal tumor originating from eccrine sweat glands. The features of ES on ultrasonography (US) have received little attention. Therefore, we report the sonographic findings in a case of an ES that originated from the abdominal wall and discuss the previously reported cases. PATIENT CONCERNS: A 53-year-old woman was admitted to our hospital with a complaint of a painful nodule on the right side of her abdominal wall of 1-year duration. DIAGNOSES: The mass on the right side of abdominal wall was diagnosed as ES by histopathological examination. INTERVENTIONS: The patient subsequently underwent total excision of the mass. OUTCOMES: The patient recovered well and had no complications during the 1-year follow-up. LESSONS: As eccrine spiradenoma (ES) is rare and most of the tumors are excised without prior imaging studies. Little is known regarding the features of ES on ultrasonography (US). Familiarizing with the clinical and US features of this rare tumor may increase awareness of the disease among sonographers and clinicians.

Poly(L-Glutamic Acid)-Drug Conjugates for Chemo- and Photodynamic Combination Therapy.

Despite the polymeric vascular disrupting agent (poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles can efficiently inhibit cancer growth, their further application is still a challenge owing to the tumor recurrence and metastasis after treatment. In this study, two poly(L -glutamic acid)-drug conjugates for chemo-and photodynamic combination therapy are fabricated. PLG-g-mPEG-CA4 nanoparticles are prepared by combretastatin A4 (CA4) and poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) using the Yamaguchi esterification reaction. PLG-g-mPEG-TPP (TPP: 5, 10, 15, 20-tetraphenylporphyrin) nanoparticles are constructed using PLG-g-mPEG and amine porphyrin through condensation reaction between carboxyl group of PLG-g-mPEG and amino group of porphyrin. The results showed that PLG-g-mPEG-CA4 nanoparticles have good antitumor ability. PLG-g-mPEG-TPP nanoparticles can produce singlet oxygen under the laser irradiation. Moreover, the combined therapy of PLG-g-mPEG-CA4 and PLG-g-mPEG-TPP nanoparticles has higher antitumor effect than the single chemotherapy or the single photodynamic therapy in vitro. The combination of CA4 nondrug and photodynamic therapy provides a new insight for enhancing the tumor therapeutic effect with vascular disrupting agents and other therapy.

Polymerization and coordination synergistically constructed photothermal agents for macrophages-mediated tumor targeting diagnosis and therapy.

Developing an ideal photothermal agent is one of the challenges for effective photothermal therapy (PTT). Herein, a green and simple yet versatile method is developed to construct a novel poly-(iron-dopamine coordination complexes) nanoparticles (P[Fe-DA]-NPs) based on polymerization and coordination synergistically by using Fe3+ ions and dopamine (DA) in aqueous solution, and simultaneously poly(vinylpyrrolidone) (PVP) is applied to improve dispersion stability. P[Fe-DA]-NPs can be laden into macrophages directly with no further purification required to target tumor tissue to perform cell-mediated strategy. P[Fe-DA]-laden macrophages as an ideal photothermal agent has the advantages of good biocompatibility, simple preparation process, high photothermal performance, and effective tumor targeting. Furthermore, the P[Fe-DA]-laden macrophages possess excellent photoacoustic imaging (PAI) capacity for guiding the precise PTT. The results show that the tumors are significantly suppressed after PTT with the help of the accurate PAI diagnosis. This cell-mediated strategy may be the most promising avenue for the future clinical cancer therapy.

Fe-TCPP@CS nanoparticles as photodynamic and photothermal agents for efficient antimicrobial therapy.

Traditional antimicrobial therapies always rely on antibiotics, which have led to the overuse of antibiotics and caused the emergence of multidrug-resistant (MDR) bacteria in recent years. In this study, an efficient and broad-spectrum antimicrobial system based on chitosan (CS)-encapsulated multifunctional metal-organic nanoparticles (Fe-TCPP@CS NPs) was constructed to integrate the electrostatic targeting property and photodynamic and photothermal antimicrobial therapies. Tetrakis (4-carboxyphenyl) porphyrin (TCPP) coordinated with Fe3O clusters to form nanoparticles, Fe3O clusters enabled low-temperature photothermal therapy as well as avoiding the porphyrins self-aggregation to ensure the singlet oxygen yield under irradiation, and CS as the outer layer covered on Fe-TCPP nanoparticles could improve the dispersibility in aqueous solution and enhance the electrostatic binding with bacterial cell membranes to improve the antibacterial activities. After simple synthesis, we successfully obtained ideal and biocompatible multifunctional nanoparticles and verified their antimicrobial properties. Under light irradiation, Fe-TCPP@CS NPs could produce enough ROS and heat to kill S. aureus, E. coli and methicillin-resistant S. aureus with a synergistic effect. Therefore, Fe-TCPP@CS NPs would be an efficient and broad-spectrum antimicrobial agent, providing a novel approach to bacterial infection therapy.

An immune cocktail therapy to realize multiple boosting of the cancer-immunity cycle by combination of drug/gene delivery nanoparticles.

Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.

Nanozyme-mediated cascade reaction based on metal-organic framework for synergetic chemo-photodynamic tumor therapy.

Numerous biological enzymes are considered promising for tumor therapy. However, the remote control of enzymatic activity in vivo to achieve a satisfactory therapeutic effect remains challenge. Herein, we loaded chlorin e6 (Ce6) to the peroxidase-mimic metal-organic framework (MOF) MIL-100 (Ce6@MIL-100) to develop cascade-reaction nanoparticles shielded with hyaluronic acid (CMH NPs). CMH NPs and the highly expressed H2O2 in the tumor site underwent Fenton reaction to generate hydroxyl radical (·OH) and O2. The produced ·OH and O2 were used for chemodynamic therapy and alleviating hypoxia, respectively. Under near-infrared light irradiation, the Ce6-mediated photochemical effect not only generated cytotoxic singlet oxygen (1O2) for enhanced photodynamic therapy with additional oxygen supply, but also produced H2O2 to amplify the Fenton reaction. Therefore, the CMH NPs exhibited a virtuous cycle of cascade reactions. Furthermore, comprehensive experiments demonstrated that combined therapy could effectively ablate tumors. Thus, the nanozyme based on MOF realized potent chemo-photodynamic therapeutic efficacy. Overall, the nanoplatform displayed an exciting biomedical application of MOF-derived nanozyme as a versatile therapeutic agent.

Poly(l-glutamic acid)-Based Zwitterionic Polymer in a Charge Conversional Shielding System for Gene Therapy of Malignant Tumors.

Recently, pH-sensitive polymers have received extensive attention in tumor therapy. However, the rapid response to pH changes is the key to achieving efficient treatment. Here, a novel shielding system with a rapidly pH-responsive polymer (PAMT) is synthesized by click reaction between poly(γ-allyl-l-glutamate) and thioglycolic acid or 2-(Boc-amino)ethanethiol. The zwitterionic biodegradable polymer PAMT, which is negatively charged at physiological pH, can be used to shield positively charged nanoparticles. PAMT is electrostatically attached to the surface of the positively charged PEI/pDNA complex to form a ternary complex. The zwitterionic PAMT-shielded complex exhibits rapid charge conversion when the pH decreases from 7.4 to 6.8. For the in vivo tumor inhibition experiment, PAMT/PEI/shVEGF injected intravenously shows a more significant inhibitory effect on tumor growth. The excellent results are mainly attributed to introduction of the zwitterionic copolymer PAMT, which can shield the positively charged PEI/shVEGF complex in physiological conditions, while the surface potential of the shielded complexes changes to a positive charge in the acidic tumor environment.