Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Advances of Amifostine in Radiation Protection: Administration and Delivery.

Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.

A Facile Way To Improve the Bioavailability of Nanomedicine Based on the Threshold Theory.

One of the most significant barriers to the clinical transformation of nanomedicines is low drug distribution in solid tumors due to quick clearance of nanomedicine after injection. Studies have revealed that the distribution of nanomedicine in tumor sites can be considerably improved when the number of nanoparticles supplied in a short period surpasses the threshold. Most routinely employed nanomaterials have dose-related safety concerns. To resolve this problem, we use highly biocompatible albumin to construct blank nanoparticles and doxorubicin loading nanoparticles. Under the guidance of the threshold theory, when the quantity of drug loading nanoparticles is constant, the drug delivery effectiveness improves with the addition of blank nanoparticles. This enhanced impact was verified both in vitro and in vivo. The area under the curve of the high dose group (19.5 × 1011) is 2.5 times higher than that of the low dose group (6.5 × 1011). In addition, the drug distribution of the high dose group at the tumor site was also improved by 1.5 times compared with the low dose group. The results of histopathological sections also showed that the administration of excess blank nanoparticles within 24 h has no damage to the animals. This study contributes to the clinical transition of nanomedicine by providing fresh ideas for anticancer nanomedicine research.

Mild Hyperthermia Induced by Hollow Mesoporous Prussian Blue Nanoparticles in Alliance with a Low Concentration of Hydrogen Peroxide Shows Powerful Antibacterial Effect.

The emergence of superbacteria as well as the drug resistance of the current bacteria gives rise to worry regarding a bacterial pandemic and also calls for the development of novel ways to combat the bacteria. Here in this article, we demonstrate that mild hyperthermia induced by hollow mesoporous Prussian blue nanoparticles (HMPBNPs) in alliance with a low concentration of hydrogen peroxide (H2O2) shows a powerful inhibition effect on bacteria. Our results demonstrate that this therapeutic regime could realize almost full growth inhibition of both Gram-positive (Staphylococcus aureus, S. aureus) and -negative bacteria (Escherichia coli, E. coli), as well as potent inhibition/elimination of the S. aureus biofilm. The wound healing results indicate that combination regime of the antibacterial system could be conveniently used for wound disinfection in vivo and could promote wound healing. To our limited knowledge, this is one of the few pioneer works to apply mild hyperthermia for the combat of bacteria, which provides a novel strategy to inspire future studies.

Progress in Intradermal and Transdermal Gene Therapy with Microneedles.

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.

Capillary electrophoretic method for Staphylococcus aureus detection by using a novel antimicrobial peptide.

A novel peptide containing antimicrobial sequence and gelatinase cleavage sites was designed for Staphylococcus aureus detection. Since Staphylococcus aureus could secrete gelatinase, the fluorescein labeled peptide GKRWWKWWRRPLGVRGC could be recognized and cleaved. The obtained products were able to be analyzed by capillary electrophoresis with fluorescence detection. To explore the effect of Staphylococcus aureus concentration on enzyme digestion ability of peptide, Staphylococcus aureus with different concentrations were incubated with the peptide. Results indicated that capillary electrophoretic method was efficient for determining Staphylococcus aureus content. Compared with traditional approaches for Staphylococcus aureus detection, capillary electrophoresis possessed higher efficiency, enhanced sensitivity, and low sample consumption. Moreover, the proposed peptide also presented desirable antimicrobial activity. It suggested that the novel antimicrobial peptide used in this research opens a new path of detecting Staphylococcus aureus by capillary electrophoretic method.

How does DNA 'meet' capillary-based microsystems?

DNA possesses various chemical and physical properties which make it important in biological analysis. The opportunity for DNA to 'meet' capillary-based microsystems is rapidly increasing owing to the expanding development of miniaturization. Novel capillary-based methods can provide favourable platforms for DNA-ligand interaction assay, DNA translocation study, DNA separation, DNA aptamer selection, DNA amplification assay, and DNA digestion. Meanwhile, DNA exhibits great potential in the fabrication of new capillary-based biosensors and enzymatic bioreactors. Moreover, DNA has received significant research interest in improving capillary electrophoresis (CE) performance. We focus on highlighting the advantages of combining DNA and capillary-based microsystems. The general trend presented in this review suggests that the 'meeting' has offered a stepping stone for the application of DNA and capillary-based microsystems in the field of analytical chemistry.

Modulation of Aggregation-Caused Quenching to Aggregation-Induced Emission: Finding a Biocompatible Polymeric Theranostics Platform for Cancer Therapy.

Dual intramolecular FRET polymers are synthesized via Suzuki coupling and their luminescence characteristics from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) is modulated conveniently by adjusting the charged ratios. The finally obtained AIE polymer is further employed to construct doxorubicin loaded nanoparticles as a promising theranostics platform for cancer therapy.

Multienzyme detection and in-situ monitoring of enzyme activity by bending CE using quantum dots-based polypeptide substrate.

Multienzyme detection and monitoring enzyme activity in situ are significant for the disease to diagnose. This study aims to develop a quantum dots (QDs)-based nanoprobe Cyanine5-DDDLEVLFQFPGLVPRGSGGHHHHHH-QDs (Cy5-LEVLVP-QD), which is able to detect two enzymes inside a bent capillary using CE. Cy5-LEVLVP and QDs were allowed to bind with each other through metal affinity interaction and then injected the Cy5-LEVLVP-QD complex into a capillary with different bends, followed by related enzyme that can cleave the Cy5-LEVLVP peptide. The fluorescence of Cy5 was excited by QDs due to Förster resonance energy transfer. By monitoring the peaks produced by the original Cy5-LEVLVP-QD complex and a significant fluorescence change, sensitive analysis of two different enzymes was conducted. Therefore, the novel approach of using capillaries with semicircular bends could prove particularly useful for enzyme investigating in disease.

Carbon dots encapsulated zeolitic imidazolate framework-8 as an enhanced multi-antioxidant for efficient cytoprotection to HK-2 cells.

Excessive reactive oxygen species (ROS) can lead to the imbalance of antioxidant system in the body and cause oxidative damage to cells. It is imperative to rationally design nanomaterials with high catalytic activity and multiple antioxidant activities. Here, line peppers-derived carbon dots (CDs) is encapsulated into zeolitic imidazolate framework-8 (CDs@ZIF-8) to achieve enhanced antioxidant activities for improved protective effect on cells. This nanosystem has a broad spectrum of antioxidant properties, which can effectively remove a variety of intracellular ROS and protect cells from ROS-induced death and cytoskeleton damage. In addition, CDs@ZIF-8 can reduce malondialdehyde (MDA) level and increase the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the level of glutathione (GSH) in human kidney proximal tubular epithelial cells (HK-2) cells. Mechanism studies demonstrated that CDs@ZIF-8 can up-regulate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), allowing the regulation of antioxidant enzymes to further achieve antioxidant effect. Besides, CDs@ZIF-8 inhibited the secretion of proinflammatory cytokines. This work demonstrates that the constructed CDs@ZIF-8 with multi-antioxidant activity can act as a highly efficient intracellular ROS scavenger and provide potential for the application in related oxidative stress-induced diseases.

Green synthesis of epigallocatechin gallate-ferric complex nanoparticles for photothermal enhanced antibacterial and wound healing.

Bacterial infections are a significant global health concern, particularly in the context of skin infections and chronic wounds, which was further exacerbated by the emerging of antibiotic resistance. Therefore, there are urgent needs to develop alternative antibacterial strategies without inducing significant resistance. Photothermal therapy (PTT) is a promising alternative approach but usually faces limitations such as the need for stable and environmental-friendly PTT agents and ensuring biocompatibility with living tissues, necessitating ongoing research for its clinical advancement. Herein, in this study, with the aim to develop a green synthesized PTT agent for photothermal enhanced antibacterial and wound healing, we proposed a facile one-pot method to prepare epigallocatechin gallate-ferric (EGCG-Fe) complex nanoparticles. The obtained nanoparticles showed improved good size distribution and stability with high reproducibility. More importantly, EGCG-Fe complex nanoparticles have additional photothermal conversion ability which can give photothermal enhanced antibacterial effect on various pathogens, including Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) strains. EGCG-Fe complex nanoparticles also showed powerful biofilm prevention and destruction effects with promoted antibacterial and wound healing on mice model. In conclusion, EGCG-Fe complex nanoparticles can be a robust green material with effective and novel light controllable antibacterial properties for photothermal enhanced antibacterial and wound healing applications.

Application of f-FeNC@GOx cascade enzyme nanomaterials in the healing of infected wounds.

AIMS: Bacterial infection is a significant factor contributing to the deterioration of wounds, and the misuse of antibiotics has exacerbated bacterial resistance. Therefore, there is an urgent need to develop a novel antibacterial strategy to replace conventional therapies. This study aims to construct a self-activated cascade reaction nanozyme, f-FeNC@GOx, which triggers a cascade reaction in the presence of glucose. This cascade reaction generates highly toxic hydroxyl radicals (OH), thereby achieving the goal of eliminating bacteria and promoting wound healing. MATERIAL AND METHODS: In vitro antibacterial experiments, bacterial spread plate method, Live/Dead staining, and crystal violet staining were conducted to analyze the antibacterial ability and mechanism of f-FeNC@GOx. In vivo experiments, a mouse wound model was established, and H&E and Masson staining of wound tissues were performed to assess the antibacterial activity of the f-FeNC@GOx in vivo. KEY FINDINGS: The in vivo and in vitro experiments confirmed that f-FeNC@GOx exhibited significant antibacterial effect against both Staphylococcus aureus and Escherichia coli in the presence of glucose. Furthermore, it showed optimal wound healing performance in the wound models. SIGNIFICANCE: These findings suggested that f-FeNC@GOx was a novel and effective antibacterial nanomaterial, which provided a promising antibacterial strategy using nanoenzyme based cascade reaction.

Hydrogels for Antitumor and Antibacterial Therapy.

As a highly absorbent and hydrophobic material with a three-dimensional network structure, hydrogels are widely used in biomedical fields for their excellent biocompatibility, low immunogenicity, adjustable physicochemical properties, ability to encapsulate a variety of drugs, controllability, and degradability. Hydrogels can be used not only for wound dressings and tissue repair, but also as drug carriers for the treatment of tumors. As multifunctional hydrogels are the focus for many researchers, this review focuses on hydrogels for antitumor therapy, hydrogels for antibacterial therapy, and hydrogels for co-use in tumor therapy and bacterial infection. We highlighted the advantages and representative applications of hydrogels in these fields and also outlined the shortages and future orientations of this useful tool, which might give inspirations for future studies.

A novel assay for the determination of PreScission protease by capillary electrophoresis.

The detection of protease activity in the body plays a significant role in the early diagnosis of diseases. However, enzymes inevitably come into contact with various complex biological fluids in the body during the flow, which greatly increases the detection difficulty. Therefore, protease detection in vivo has great challenges. Herein, we report a new assay for detecting protease using capillary electrophoresis inside a capillary with semicircular bends. We first designed a peptide substrate, and then the peptide was self-assembled with quantum dots to form a QDs-peptide substrate. The capillary was bent to semicircular-shaped turns and served as a micro-reactor to allow protease and substrate react in it. Due to the different electrophoretic velocity, the protease and the substrate were mixed inside the bent capillary with sequential injections and the cleavage of the substrate can be detected using capillary electrophoresis combined with Förster resonance energy transfer technology. This novel assay will greatly expand the detection of enzyme activity in vivo.

Liposome Loaded Ion/Temperature Dual Responsive Gellan Gum Hydrogel as Potential Nasal-To-Brain Delivery System.

Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.

Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer.

Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K's indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

Temperature-Ion-pH Triple Responsive Gellan Gum as In Situ Hydrogel for Long-Acting Cancer Treatment.

BACKGROUND: Promising cancer chemotherapy requires the development of suitable drug delivery systems (DDSs). Previous research has indicated that a hydrogel is a powerful DDS for tumor therapy and holds great potential to offer a feasible method for cancer management. METHODS: In this study, glutathione-gellan gum conjugate (GSH-GG) was synthesized through chemical reaction. Doxorubicin hydrochloride (DOX) was loaded into GSH-GG to accomplish DOX-loaded GSH-GG. The properties, injectability, drug release, and in vitro and in vivo anticancer effects of DOX-loaded GSH-GG were tested. RESULTS: DOX-loaded GSH-GG showed a temperature-ion dual responsive gelling property with good viscosity, strength, and injectability at an optimized gel concentration of 1.5%. In addition, lower drug release was found under acidic conditions, offering beneficial long-acting drug release in the tumor microenvironment. DOX-loaded GSH-GG presented selective action by exerting substantially higher cytotoxicity on cancer cells (4T1) than on normal epithelial cells (L929), signifying the potential of complete inhibition of tumor progression, without affecting the health quality of the subjects. CONCLUSIONS: GSH-GG can be applied as a responsive gelling material for delivering DOX for promising cancer therapy.

Polymerized Tannic Acid Offers a Nanosized Platform to Combat Bacterial Infection.

Worldwide antibiotic abuse accelerates the evolution of drug-resistant super bacteria, which goes against the war toward bacterial infection. Antibiotic-loaded nanoparticles as a typical form of nanomedicine hold great promise in combating bacterial infection, which requires the development of a suitable carrier. Tannic acid (TA) showed an inhibition effect on both Gram-positive and -negative strains; however, there are no reports on the development of antibacterial nanoformulations based on TA itself. We could get PTA NPs using a one-pot method, and their size and ζ-potential were characterized. Herein, we carefully tuned the polymerization of TA to give well-dispersed polytannic acid nanoparticles (PTA NPs) with a size of 100 nm. Moreover, our results demonstrated that PTA NPs showed enhanced antibacterial effects on both Gram-positive and -negative strains as compared to free TA. Especially, PTA NPs can preferably accelerate the healing of Staphylococcus-infected wounds. Based on its structure, we suggested that PTA NPs may have a similar property to polydopamine nanoparticles to offer high drug loading for potential combination therapy for extended application in bacterial infection management.

Degradable microneedle patches loaded with antibacterial gelatin nanoparticles to treat staphylococcal infection-induced chronic wounds.

Infection-induced chronic wounds cause prolonged pains, a high risk of amputation, and even increased mortality in immunocompromised patients. Here we report an antibacterial microneedle (MN) patch, which features high degradability in biological fluids and gelatinase-responsive release of an antibacterial photothermal peptide AMP-Cypate. We first synthesize gelatin nanoparticles (GNPs) and then conjugate the AMP-Cypate to afford composite AMP-Cypate@GNPs. The proteinaceous nanoparticles can responsively release AMP-Cypate in the presence of gelatinase, an enzyme secreted specifically by Staphylococcus aureus (S. aureus). AMP-Cypate@GNPs were then deposited in the tips of MNs fabricated by PVP and recombinant human type III collagen (Col III) to devise the antibacterial MN/AMP-Cypate@GNP patches. When applied to the infection site, MNs break through the epidermis and the stratum corneum, dissolve in the infected dermis, reach the bacterial colony or biofilm, release AMP-Cypate@GNPs, and exert a gelatinase-responsive photothermal therapy under near-infrared (NIR) irradiation to kill the pathogen S. aureus. In a rat model of staphylococcal infection-induced chronic wounds mimicking the condition of diabetic foot ulcer, the antibacterial MN/AMP-Cypate@GNP patches eradiated the bacterial infection and resulted in complete healing of the wounds, proving its potential application in the treatment of chronic wound infections and diabetic foot ulcers.

Nanodot-doped peptide hydrogels for antibacterial phototherapy and wound healing.

Bacterial infection of wounds delays the healing process, increases the risk of chronic trauma associated with pain and complications, and offers a breeding ground for drug-resistant bacteria. A rapid and effective eradication of the bacterial species in the wound area is thus important. Herein, we designed a phototherapeutic antibacterial platform based on peptides and copper sulfide nanodots (CuS NDs) for multi-mechanistic eradication of bacteria colonized on the wound surface. The antimicrobial peptide weaves into a network in the form of a hydrogel, which supports CuS NDs to generate heat and produce reactive oxygen species (ROS) under the irradiation of near-infrared light (NIR). The heat and ROS generated in situ act as non-contact-based antibacterial factors and together with contact-based antimicrobial peptides cause irreversible membrane destruction, cell content damage, and thermal ablation of the bacteria. Lastly, nanodot-doped peptide hydrogels combined with collagen showed complete bacterial elimination and significantly accelerated wound healing in a splint-fixed mouse infection model.