Novel active-targeting nano-therapeutic, Temozolomide-loaded magnetosomes conjugate has been developed to address the challenges of high metastatic rates and recurrence of tumors due to tumor circulating cells. Temozolomide-loaded magnetosomes as drug conjugate were characterized through a scanning electron microscope, Zeta-sizer, and UV-visible spectroscopy. The anti-tumor activity was studied in vitro (Cell viability, Cell proliferation, and flow cytometry) and in vivo (Xenograft tumor model). The particle size of temozolomide-coated magnetosomes is larger than that of uncoated magnetosomes. The zeta potential decreased to -11.2 from -21.6 mV for Temozolomide- magnetosomes conjugates. The drug-coated magnetosomes can sustain drug release, reducing the frequency of administration and enhancing their therapeutic effect. The study found that Temozolomide-loaded magnetosomes conjugate showed enhanced tumor cytotoxicity and apoptosis than free Temozolomide or magnetosomes. In vivo, the treatment of mice with Temozolomide-loaded magnetosomes inhibited tumor growth to 405.25 mm and reduced tumor weight (0.60 g), with fewer juvenile cells and increased necrotic area. These results suggest Bacterial magnetosomes as an appropriate choice for cancer therapy since they may be superior drug carriers with increased therapeutic efficacy and no undesirable side effects to the brain.

Photothermal therapy (PTT) is an emerging cancer therapeutic modality displaying the great potential to clinical patients. However, the conventional PTT is suffering from restrictions of heat resistance of tumor cells (e.g. the overexpression of heat shock proteins, HSPs) and adverse effects to normal cells. To break the shackles, herein, a hypoxia-responsive theranostic nanoplatform (GA/BN LIP) was designed for achieving synergistic chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT) through overcoming heat-shock response, while enabling fluorescence tracing. The GA/BN LIP consisted of a hypoxia-responsive liposomal material (DSPE-AZO-PEG) as the shell, surface-functionalized with cRGD peptides targeted binding to integrin αβ receptor expressed in tumors. The GA/BN LIP co-delivered gambogic acid (GA) as HSP90 inhibitor and hypoxia-responsive photosensitizer Bcy-NO. After GA/BN LIP entering tumor cells by integrin αβ receptor-mediated endocytosis, drugs were specifically released in response to hypoxic conditions due to lysis of liposomes. GA not only directly killed tumor cells to realize chemotherapy, but also sensitized tumor cells to PTT by downregulating HSP90 protein expression, meantime Bcy-NO targeted mitochondria for combined PTT and PDT. Intriguingly, the reduction of Bcy-NO by nitroreductase (NTR) resulted in the restoration of fluorescence, achieving real-time monitoring of the theranostic process in live cells. In conclusion, this theranostic system, designed to target the hypoxic tumor microenvironment, utilized a sensitization mechanism to enhance the synergistic effects of chemo/PTT/PDT therapy, resulting in improved antitumor efficacy in both in vitro and in vivo studies.

The effective measure to promoting endothelial repair is to construct a surface similar to that of normal vascular on blood contact materials. The construction of cell culture platform regulating platelets, endothelial cells (ECs) and Smooth muscle cells (SMCs) may provide more help to promote endothelial repair. In this work, a novel versatile cell research platform UV-P-PDA@TiO was constructed by magnetron sputtering and photoetching. The surface of UV-P-PDA@TiO was evaluated by materials science methods such as FTIR, Raman, Micro BCA and WCA, and cell culture was performed on the surface. These results indicated that UV-P-PDA@TiO platform regulated the cellular behavior of platelets, ECs, and SMCs, achieved selective adhesion, and exhibited orientation. The advantage of histocompatibility was demonstrated by in vivo tests that UV-P-PDA@TiO had pattern stability and inhibited tissue proliferation. Conceivably, the regulating the multicellular UV-P-PDA @ TiO culture platform may provide a versatile surface engineering strategy for biomaterials.

Mitigation of adriamycin (ADR)-induced nephropathy remains a significant challenge in clinical management. Brain-targeted administration of losartan demonstrates comparable nephroprotective effects at a 1:500 concentration relative to gavage administration. This study established an exosome-based nano-delivery platform (ExoACP) to reduce drug dosage for alleviating ADR-induced nephropathy. The platform was rigorously tested for toxicity and blood-brain barrier penetration. Additionally, the role and possible mechanism of ExoACP-Los in alleviating ADR-induced nephropathy in mice were investigated. ExoACP showed enhanced penetration in brain microvascular endothelial cells, with a 7.20-fold increase in uptake. In the ADR model, ExoACP-Los exhibited anti-inflammatory and anti-fibrotic effects by downregulating the renin-angiotensin system, reducing extracellular matrix deposition by nearly half. These findings suggest ExoACP-Los can alleviate ADR-induced nephropathy by enhancing targeted drug delivery to the brain while reducing losartan. Overall, ExoACP holds significant potential for future clinical applications in chronic nephropathy.

Exploiting the unique physiological and biochemical characteristics of the tumor microenvironment, the development of a polypeptide nanogel capable of responding to these specific properties holds great promise as an effective antitumor strategy. In this study, we synthesized a glutathione-responsive (GSH-responsive) methylated poly (ethylene glycol)-poly (phenylalanine)-poly (cystine) block copolymer (mPPC) through one-step ring-opening polymerization. Shikonin (SHK) was encapsulated within nanogel, designated as mPPC/SHK. The biocompatible and safe nature of mPPC facilitated its accumulation at the tumor site through enhanced permeability and retention effect, leading to efficient release of SHK upon stimulation by high concentrations of GSH. As anticipated, the group of mPPC/SHK displayed enhanced efficacy against tumors, resulting in a tumor inhibition rate of 69.97 % in the 4T1 breast cancer model. Overall, this GSH-responsive polypeptide nanogel encapsulating SHK has tremendous potential as a promising biomedical agent for effective tumor nanotherapy.

Diabetes mellitus is a chronic metabolic disease that increasingly affects people every year. It is known that with its progression and poor management, metabolic changes can lead to organ dysfunctions, including kidneys. The study aimed to combine Raman spectroscopy and biochemical lipid profiling, complemented by machine learning (ML) techniques to evaluate chemical composition changes in kidneys induced by Type 2 Diabetes mellitus (T2DM). Raman spectroscopy identified significant differences in lipid content and specific molecular vibrations, with the 1777 cm band emerging as a potential spectroscopic marker for diabetic kidney damage. The integration of ML algorithms improved the analysis, providing high accuracy, selectivity, and specificity in detecting these changes. Moreover, lipids metabolic profiling revealed distinct variations in the concentration of 11 phosphatydylocholines and 9 acyl-alkylphosphatidylcholines glycerophospholipids. Importantly, the correlation between Raman data and lipids metabolic profiling differed for control and T2DM groups. This study underscores the combined power of Raman spectroscopy and ML in offering a low-cost, fast, precise, and comprehensive approach to diagnosing and monitoring diabetic nephropathy, paving the way for improved clinical interventions. However, taking into account small number of data related to ethical committee approvals, the study should be verified on a larger number of cases.

Bee venom acupuncture (BVA) offers therapeutic potential for rheumatoid arthritis (RA) but faces challenges from pain and allergies linked to live bee stings. A key hurdle is melittin (Mel), bee venom's main anti-inflammatory component, which degrades rapidly when orally ingested, leading to decreased efficacy and increased toxicity. This study proposes a solution by encapsulating melittin in liposomes to enhance stability and lessen side effects, expanding its clinical applicability. Additionally, the advancement of microneedle technology, which bypasses gastrointestinal issues by targeting the stratum corneum, opens a novel pathway for RA treatment. Employing soluble microneedles loaded with melittin-encapsulated liposomes (Mel-Lip) enables effective transdermal delivery. Results from an adjuvant-induced RA animal model show that Mel-Lip microneedles improve foot health, repair cartilage, and lower inflammatory markers, highlighting microneedling with transdermal nanocarriers as a promising, patient-friendly approach for RA management.

More effective drug formulations are needed to increase the selectivity and efficacy of available chemotherapeutics. We have previously shown that nanoparticles decorated with the tumour homing peptide CGKRK can selectively deliver payloads to the placenta. In this study, we investigated whether two novel placental homing peptides NKGLRNK (NKG) and RSGVAKS (RSG) can be utilized to selectively deliver doxorubicin (DOX) to breast cancer cells. Fluorescence microscopy and flow cytometry showed that NKG and RSG bind to and accumulate in MDA-MB-231 and MCF-7 cells in a time-dependent manner, to a similar extent as CGKRK, but accumulate in healthy MCF-10A cells to a much lesser degree. NKG- and RSG-decorated liposomes facilitated equivalent delivery of DOX to MDA-MB-231 and MCF-7 cells, with a comparable efficacy to CGKRK-decorated liposomes. These findings suggest that NKG and RSG represent novel breast tumour-binding sequences that could be utilized to develop more efficacious targeted breast cancer therapies.

Nucleic acid drug delivery remains a key challenge in the development of nucleic acid therapy. How to improve the efficiency of nucleic acid delivery is still an important strategy for Lipofectamine 3000 and LNP development. Here, we screened 248 inhibitors or agonists related to immune modulation and identified three small molecules (BP-1-102, SCH58261, and Bropirimine) that could enhance the transfection efficiency to 2-fold to 5-fold of Lipofectamine 3000 and LNP, all of which are currently approved for clinical use in the treatment of the most common malignant tumors. In addition, we used high-throughput RNA sequencing technology to analyze the mechanisms and found that they were mainly associated with the receptor-mediated endocytosis pathway. Our findings have yielded novel insights that can contribute to the advancement of nucleic acid drugs, enhancing both their efficacy and precision in targeting cancer therapy.

Nanoemulsions are nanostructured material and stabilized colloidal in nature evolved as a highly desirable mechanism for the delivery of drugs. Our objective of the study deals with a successful Rivastigmine (RSG) loaded nanoemulsion which can effectively progress the treatment of AD patients. We developed nanoemulsion containing RSG by combining pyridoxine, an essential vitamin supplement for central nervous system development, with linseed oil, which functioned as the lipophilic phase in the nanoemulsion formulation. The optimal formulation having globular size of 202.3 nm was further evaluated by various analytical techniques, including zeta potential analysis, ATR, DSC, and XRD study. The study utilized the Morris Water Maze (MWM) model to assess the cognitive abilities of Long-Evans rats. The current investigation establishes that the utilization of RSG nanoemulsion incorporating blend of linseed oil and pyridoxine which reduced travel distance in animal mode and can be successfully contribute to therapeutic advancements in patients with AD.

Among hospital-acquired infections, Pseudomonas aeruginosa-associated urinary tract infections (UTIs) are mainly caused by indwelling urethral catheters (catheter-associated UTIs or CAUTIs) and are difficult to treat, resulting in high rates of morbidity among hospitalized patients. While antibiotics can successfully treat bacteria in the bladder lumen, they are inefficient at crossing stratified urothelium plasma membranes to kill persistent intracellular bacterial communities (IBCs). Herein, we introduce an approach to target UTI IBCs by locally delivering the antibiotic gentamicin via polymeric nanogels conjugated with a cell-penetrating peptide Cys-Gly-Lys-Arg-Lys. This novel approach delivered ~36 % more intracellular gentamicin compared to drug delivered in solution in vitro. In an acute UTI murine model, the nanogel cell-penetrating peptide drug delivery system facilitated the transport of gentamicin into the urothelium and resulted in >90 % clearance of a uropathogenic P. aeruginosa clinical strain in vivo.

Iron oxide nanoparticles are a promising candidate for the dual-mode MRI contrast agent, however most of them have limited circulation time and predominant negative contrast. We developed citric acid stabilized superparamagnetic maghemite nanoparticles (CA-SPMNs) with size 3.2 ± 0.7 nm with intense positive contrast. Co-precipitation reactions under well-controlled conditions in the automatic chemical reactor have carried out the synthesis. We found an encouraging correlation between aggregate formation kinetics in biological media and in vitro cytotoxicity results and in vivo circulation time. A cytotoxicity test showed the mouse fibroblast viability over 80 % for iron doses exceeding 1 mg/mL. CA-SPMNs have a low r/r ratio, exhibiting positive contrast. Using in vivo MRI we demonstrated that CA-SPMNs circulate in the blood for 12-24 h, enabling blood vessel and tumor visualization, and partial renal clearance. Finally, CA-SPMNs show promise as effective MRI contrast agents, enabling differentiation between normal and pathological tissues.

Growing interest in cancer radiotherapy has led to the application of nanoparticles as radiosensitizers. Here, we, for the first time, present the results of the radiosensitizing properties of silver nanoparticles (AgNPs) (possessing low toxicity towards human body) against cancer cells under neutron irradiation. Five standard cancer cultures (including glioblastoma, known for its resistance to conventional photon radiation) were used to evaluate the radiosensitizing properties of AgNPs suing MTT test, flow cytometry, and optical fluorescence microscopy. Neutron irradiation was applied in the absorbed dose of 0.5-1.5 Gy with an average neutron energy of 7.5 MeV. AgNPs increased the irradiation efficiency with the radiosensitivity enhancement ratios 1.02-2.32, for glioblastoma with ratios 1.22-1.47. It was revealed that at 1.5 Gy, AgNP-induced cytotoxicity made a significant contribution to the total observed radiosensitizer effect: on average, for five cell types, 29.8 and 96.2 % at the AgNP concentration of 0.2 and 1.6 μg/mL, respectively.

The tear fluids from three healthy individuals and three patients with diabetes mellitus were examined using atomic force microscopy-infrared spectroscopy (AFM-IR) and Fourier transform infrared spectroscopy (FTIR). The dried tear samples showed different surface morphologies: the control sample had a dense network of heart-shaped dendrites, while the diabetic sample had fern-shaped dendrites. By using the AFM-IR technique we identified spatial distribution of constituents, indicating how diabetes affects the structural characteristics of dried tears. FTIR showed that the dendritic structures gradually disappeared over time due to glucose-induced lysozyme damage. The tear fluid from diabetes mellitus patients has a higher concentration of glucose, which accelerates the breakdown of lysozyme and, as a result, the quick loss of the dendritic structure. Our study shows that analysis of dry tear fluid can be promising technique for the detection of glycated proteins that reveal long lasting hyperglycemia and diabetes mellitus.

Disulfiram (DSF), as a sixpenny drug for the treatment of alcohol dependence, has demonstrated copper-dependent chemotherapy (CT) effects in recent years. However, as the most common modality in clinical treatment, prolonged use of CT will lead to multidrug resistance (MDR). In this work, a versatile and ingenious nanoparticle Cu/ZIF-8@DSF@GOx/HA (CZDGH) was constructed to deliver DSF, Cu and GOx to tumor cells. Once internalized by tumor cells, GOx depletes glucose blocking the energy supply leading to ST. Then DSF chelates with Cu in situ to generate CuETs, achieving toxicity-intensified CT, the reduced ATP in this process also inhibits the efflux function of P-gp. In the meantime, Cu consumes glutathione (GSH) to enhance oxidative stress, and the converted Cu catalyzes internal and external sources of HO into •OH, heightening chemodynamic therapy (CDT). The experimental results demonstrate remarkable multimodal synergistic anticancer effects that overcome MDR.

Thanatin, a potent cationic antimicrobial peptide, has demonstrated remarkable efficacy against new NDM-1 producing bacteria. However, its clinical application is hampered by suboptimal stability in circulation and limited bioavailability in the human body. To overcome these challenges, a novel thanatin nanomedicine has been developed, which encapsulated thanatin in nanoparticles formed by electrostatic interactions between negatively charged HA and PLGA. The obtained ThaNPs demonstrated good stability, low cytotoxicity, and good metabolic ratio. ThaNPs significantly improve the stability of thanatin in the circulation, increasing its half-life in 50 % serum from 0.6 h to 3.2 h. Notably, the protective effect of ThaNPs against sepsis induced by NDM-1-producing Escherichia coli. was 10-fold higher than that of unencapsulated thanatin. These findings suggest that hyaluronic acid-based nanoparticles have the potentiality to overcome the clinical limitations associated with cationic antimicrobial peptides, thereby providing a novel and effective strategy for treating severe infections caused by antibiotic-resistant bacteria.

Neutrophils are essential for innate immunity, using mechanisms like Neutrophil Extracellular Trap (NET) formation to fight pathogens. Aggregated NETs (aggNETs) help resolve inflammation by cleaving pro-inflammatory cytokines, while scattered NETs can exacerbate inflammation, leading to tissue damage. Co-injection of 10 nm nanodiamonds (ND10) with peptide antigens boosts immune responses, including anti-SARS-CoV-2 immunity, due to transient immune responses induced by aggNETs around ND10 particles. Diamond nanoparticles in adjuvant mixtures enhance vaccines, though the optimal dose is uncertain. Our study aimed to find the minimal ND10 amount needed for effective aggNETs formation and a robust immune response with minimal long-term tissue damage. In vivo experiments revealed 1 mg of ND10 per injection significantly enhances immune responses, forming granulomas rich in neutrophil elastase. Lower doses left scattered nanoparticles, insufficient for aggNETs formation. The effective ND10 dose for mice, 1 mg per injection, can be extrapolated to other organisms.

Photothermal therapy is a novel and promising method for cancer treatment due to its controllable property, noninvasive nature, and high selectivity. Nevertheless, tumor recurrence of inflammatory response and tumor tolerance of heat shock protein over-expression remain serious challenges in current photothermal therapy. Additionally, the high dosage requirement of nanomaterial for optimal imaging and therapeutic effect would result in various side effects, organ excretion burdens, and long-term accumulation in the body. In this work, RD/Qu nanoplatform is designed and prepared with near-infrared (NIR) absorbance, high photothermal conversion efficiency, and great chemotherapy effect for synergetic cancer chemo/photothermal therapy at an ultralow-dose. More importantly, both in vitro and in vivo studies demonstrate that it could decrease the expression of HSP70 to fight hyperthermia tumor tolerance and inhibit inflammatory factor COX-2 to suppress tumor recurrence. Therefore, the RD/Qu nanoparticles show excellent outcome in tumor ablation at a quite low dosage, providing a promising avenue for cancer treatment.