Nanomedicine : nanotechnology, biology, and medicine最新文献

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^-1 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-10 A 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.

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.

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.

Orthopaedic medicine often treats intervertebral disc degeneration (IVDD), which is caused by nucleus pulposus (NP) tissue damage and mechanical stress. Bioactive glasses (BGs), widely used for bone regeneration, can incorporate therapeutic ions into their network. Manganese (Mn) activates human osteoblast integrins, proliferation, and spreading. The CMnBGNPs-NPMSCs are carboxymethyl cellulose hydrogels functionalized with MnBGsNPs and NP-derived mesenchymal stem cells to treat IVDD. To ensure stability and biocompatibility of CMnBGNPs-NPMSCs were characterized for rheological properties like gelation time and swelling ratio. Gene expression analysis of PAX1, FOXF1, CA12, HBB, and OVOS2 via qRT-PCR further assessed the hydrogel's characteristics. Rat models with induced IVDD had hydrogel-MSC composite injected into their intervertebral discs for in vivo studies. Histological examination, immunohistochemical staining for inflammation and disc regeneration markers, and disc height assessments assessed therapeutic efficacy. CMnBGNPs-NPMSCs show promising results for IVDD treatment, offering a novel therapeutic strategy with clinical implications for degenerative disc diseases.

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, Cu²⁺ and GOx to tumor cells. Once internalized by tumor cells, GOx depletes glucose blocking the energy supply leading to ST. Then DSF chelates with Cu²⁺ 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, Cu²⁺ consumes glutathione (GSH) to enhance oxidative stress, and the converted Cu⁺ catalyzes internal and external sources of H₂O₂ into •OH, heightening chemodynamic therapy (CDT). The experimental results demonstrate remarkable multimodal synergistic anticancer effects that overcome MDR.

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.