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Journal of Biomedical Research May 2024Glioblastoma multiforme (GBM) presents significant challenges in treatment, with current standard-of-care approaches offering limited efficacy and survival benefits....
Glioblastoma multiforme (GBM) presents significant challenges in treatment, with current standard-of-care approaches offering limited efficacy and survival benefits. This necessitates the development of innovative therapeutic strategies to enhance treatment outcomes. Nanotechnology has emerged as a promising avenue in cancer therapy, offering targeted drug delivery and enhanced therapeutic efficacy. Polymeric nanoparticles, particularly those based on Poly (lactic-co-glycolic acid) (PLGA), have gained traction as drug carriers due to their biocompatibility and controlled release properties. However, their interception by macrophages poses challenges to effective drug delivery. Superparamagnetic iron oxide (SPIO) nanoparticles have shown promise as radiosensitizers, enhancing the efficacy of radiotherapy through the generation of reactive oxygen species (ROS). Moreover, cell membrane biomimetic drug delivery systems have garnered attention for their ability to improve biocompatibility and targeting capabilities. Leveraging these concepts, our study introduces a novel multifunctional platform, GM@P (T/S), comprising polymeric nanoparticles coated with cancer cell membrane. By encapsulating temozolomide (TMZ) and SPIO nanoparticles within GM@P (T/S), we aim to synergistically enhance the cytotoxic effects of chemotherapy and radiotherapy against GBM while overcoming limitations associated with conventional treatments. This innovative approach holds promise for addressing the unmet clinical needs in GBM therapy and advancing towards more effective and personalized treatment strategies.
PubMed: 38812286
DOI: 10.7555/JBR.38.20240100 -
Journal of Nanobiotechnology May 2024Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to...
BACKGROUND
Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor.
METHODS
A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining.
RESULTS
In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8 T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model.
CONCLUSION
MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.
Topics: Animals; Triple Negative Breast Neoplasms; Toll-Like Receptor 7; Toll-Like Receptor 8; Mice; Female; Humans; Cell Line, Tumor; Tumor Microenvironment; Nanoparticles; Transcription Factors; Mice, Inbred BALB C; Cell Cycle Proteins; Immunotherapy; Epigenesis, Genetic; Bromodomain Containing Proteins
PubMed: 38811964
DOI: 10.1186/s12951-024-02525-1 -
RSC Advances May 2024Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider... (Review)
Review
Chromones are well known as fundamental structural elements found in numerous natural compounds and medicinal substances. The Schiff bases of chromones have a much wider range of pharmacological applications such as antitumor, antioxidant, anti-HIV, antifungal, anti-inflammatory, and antimicrobial properties. A lot of research has been carried out on chromone-based copper(ii) Schiff-base complexes owing to their role in the organometallic domain and promise as potential bioactive cores. This review article is centered on copper(ii) Schiff-base complexes derived from chromones, highlighting their diverse range of pharmacological applications documented in the past decade, as well as the future research opportunities they offer.
PubMed: 38808245
DOI: 10.1039/d4ra00590b -
World Journal of Psychiatry May 2024Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum...
BACKGROUND
Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression.
AIM
To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women.
METHODS
Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared.
RESULTS
No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment ( > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S ( < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S ( < 0.05).
CONCLUSION
Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.
PubMed: 38808091
DOI: 10.5498/wjp.v14.i5.678 -
Journal of Nanobiotechnology May 2024Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4)...
BACKGROUND
Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC.
RESULTS
Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO were encapsulated in MVs (Rof&MnO@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia.
CONCLUSIONS
A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.
Topics: Animals; Aminopyridines; Mice; Cyclic AMP; Probiotics; Cyclopropanes; Manganese Compounds; Benzamides; Oxides; Macrophages; Phosphodiesterase 4 Inhibitors; Colitis; RAW 264.7 Cells; Escherichia coli; Tumor Necrosis Factor-alpha; Mice, Inbred C57BL; Male; Disease Models, Animal
PubMed: 38807127
DOI: 10.1186/s12951-024-02558-6 -
Matrix Biology Plus Jun 2024The pancreatic islet is surrounded by ECM that provides both biochemical and mechanical cues to the islet β-cell to regulate cell survival and insulin secretion....
The pancreatic islet is surrounded by ECM that provides both biochemical and mechanical cues to the islet β-cell to regulate cell survival and insulin secretion. Changes in ECM composition and mechanical properties drive β-cell dysfunction in many pancreatic diseases. While several studies have characterized changes in islet insulin secretion with changes in substrate stiffness, little is known about the mechanotransduction signaling driving altered islet function in response to mechanical cues. We hypothesized that increasing matrix stiffness will lead to insulin secretion dysfunction by opening the mechanosensitive ion channel Piezo1 and disrupting intracellular Ca dynamics in mouse and human islets. To test our hypothesis, mouse and human cadaveric islets were encapsulated in a biomimetic reverse thermal gel (RTG) scaffold with tailorable stiffness that allows formation of islet focal adhesions with the scaffold and activation of Piezo1 in 3D. Our results indicate that increased scaffold stiffness causes insulin secretion dysfunction mediated by increases in Ca influx and altered Ca dynamics via opening of the mechanosensitive Piezo1 channel. Additionally, inhibition of Piezo1 rescued glucose-stimulated insulin secretion (GSIS) in islets in stiff scaffolds. Overall, our results emphasize the role mechanical properties of the islet microenvironment plays in regulating function. It also supports further investigation into the modulation of Piezo1 channel activity to restore islet function in diseases like type 2 diabetes (T2D) and pancreatic cancer where fibrosis of the -islet ECM leads to increased tissue stiffness and islet dysfunction.
PubMed: 38803329
DOI: 10.1016/j.mbplus.2024.100148 -
Bioactive Materials Sep 2024Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or...
Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.
PubMed: 38800720
DOI: 10.1016/j.bioactmat.2024.05.019 -
National Science Review Jun 2024Vesicle, a microscopic unit that encloses a volume with an ultrathin wall, is ubiquitous in biomaterials. However, it remains a huge challenge to create its inorganic...
Vesicle, a microscopic unit that encloses a volume with an ultrathin wall, is ubiquitous in biomaterials. However, it remains a huge challenge to create its inorganic metal-based artificial counterparts. Here, inspired by the formation of biological vesicles, we proposed a novel biomimetic strategy of curling the ultrathin nanosheets into nanovesicles, which was driven by the interfacial strain. Trapped by the interfacial strain between the initially formed substrate Rh layer and subsequently formed RhRu overlayer, the nanosheet begins to deform in order to release a certain amount of strain. Density functional theory (DFT) calculations reveal that the Ru atoms make the curling of nanosheets more favorable in thermodynamics applications. Owing to the unique vesicular structure, the RhRu nanovesicles/C displays excellent hydrogen oxidation reaction (HOR) activity and stability, which has been proven by both experiments and DFT calculations. Specifically, the HOR mass activity of RhRu nanovesicles/C are 7.52 A mg at an overpotential of 50 mV at the rotating disk electrode (RDE) level; this is 24.19 times that of commercial Pt/C (0.31 mA mg). Moreover, the hydroxide exchange membrane fuel cell (HEMFC) with RhRu nanovesicles/C displays a peak power density of 1.62 W cm in the H-O condition, much better than that of commercial Pt/C (1.18 W cm). This work creates a new biomimetic strategy to synthesize inorganic nanomaterials, paving a pathway for designing catalytic reactors.
PubMed: 38800666
DOI: 10.1093/nsr/nwae153 -
Acta Pharmaceutica Sinica. B May 2024[This corrects the article DOI: 10.1016/j.apsb.2021.01.011.].
[This corrects the article DOI: 10.1016/j.apsb.2021.01.011.].
PubMed: 38799636
DOI: 10.1016/j.apsb.2024.02.013 -
Acta Pharmaceutica Sinica. B May 2024Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new...
Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the "self-guidance system", Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.
PubMed: 38799627
DOI: 10.1016/j.apsb.2023.11.019