Advanced Therapeutics最新文献

Traditional approaches for treating wound infections often involve the use of chitosan or hyaluronic acid as carriers for antibacterial agents. In contrast, an innovative method is devised for wound infection management that synergizes photodynamic therapy (PDT) with novel functional matrix materials. This new strategy offers multiple benefits, such as reduced secondary damage to the wound area, a multifaceted antibacterial mechanism, and enhanced moisturization and biocompatibility. The method employs a novel organic semiconductor nanoparticle (OSN) capable of mediating PDT, which is integrated with silk fibroin (SF), perfluorosulfonic acid (PFSA), and agar. Silk fibroin is demonstrated to effectively induce macrophage aggregation, while PDT can further activate these immune cells. The inclusion of PFSA bestows the hydrogel with moisturizing and porous characteristics. Both in vivo and in vitro antibacterial assays confirm the efficacy of PDT in eliminating bacteria, and mouse wound infection model studies show that the hydrogels significantly enhance wound healing and hair follicle regeneration. This novel hydrogel dressing holds promise as an advanced wound care solution, with substantial potential for promoting hair follicle regeneration and providing effective sterilization.

Improving the prognosis for patients diagnosed with aggressive tumors remains a critical challenge in clinical oncology. One crucial aspect of addressing this challenge involves the development of preclinical models that can accurately predict the effectiveness of potential therapies for clinical application. A pivotal element in enhancing these models lies in their ability to accurately recapitulate the tumor microenvironment. In this review, the authors focus on investigating the tumor microenvironment in the context of ex vivo glioma modelling, with a specific emphasis on the extracellular matrix. The review discusses the changes that occur within the extracellular matrix of pediatric and adult gliomas. Furthermore, it explores the potential of advanced cellular models, particularly those employing bioprinting technologies, to replicate the extracellular matrix ex vivo.

Alginate-coated silicone implants containing anti-solvent crystallized paclitaxel aim to prevent breast cancer recurrence and mitigate fibrosis around the implant. This approach represents a significant advance in breast reconstruction by utilizing 3D printed molds tailored to the shape of the implant for precise and uniform gel mixture coating. This is reported by Hyun-Wook Kang and co-workers in article number 2300358.

The glymphatic system within the central nervous system (CNS) facilitates the exchange and elimination of cerebrospinal fluid (CSF) and interstitial fluid (ISF), aiding in the removal of potentially poisonous metabolic wastes to maintain brain stability. Sleep and Aquaporin-4 (AQP-4) expression positively regulate the glymphatic system. When sleep is disturbed and AQP-4 polarization is inhibited, the glymphatic system is impaired, leading to the inability to effectively eliminate soluble wastes from the brain. This disruption can potentially contribute to, or accelerate, the progression of various CNS diseases, such as Alzheimer's disease and Parkinson's disease, as well as non-CNS diseases, like diabetes mellitus and hypertension. Therefore, the normal functioning of the glymphatic system is essential for the recovery from both CNS diseases and non-CNS diseases. In this review, an overview of the constituents and functions of the glymphatic system in the brain, specifically highlighting the glymphatic system lesions in different diseases is provided. Additionally, currently unresolved questions pertaining to this topic are summarized. Ultimately, the cerebral glymphatic system is expected to be a novel and promising target for the diagnosis and treatment of multiple diseases.

Intravesical instillation-based immunotherapy for bladder-preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano-formulations of immunological adjuvant-fluorinated chitosan (FCS) and therapeutic antibody-FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)-flubendazole (FBZ) complex and anti-PD-1 (αPD-1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ-BSA and αPD-1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment-responsive charge reversal and BSA carrier-broken effects to drive tumor-targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL-12/IFN-γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD-1/FCS nano-formulations can significantly activate the tumor immune microenvironment, especially CD8⁺ T cell infiltration and αPD-1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder-preserving treatment against BCa.

Phototherapy has emerged as a promising technique for cancer treatment, offering high efficiency and minimal side effects. Nevertheless, conventional phototherapy agents suffer from low targetability and inefficient delivery. Here, a novel approach is proposed using helical hydrogel motors fabricated by combining polyvinyl alcohol, melamine, water, and Fe₃O₄ nanoparticles. These magnetic motors are capable of precise therapy on tumor cells driven by an external magnetic field. By converting light into heat upon near-infrared illumination, the motors elevate the temperature of the targeted region, resulting in a significant therapeutic effect, with over 60% eradication of HeLa cells achieve under 808 nm near- infrared light (1.5 W cm⁻²). These helical micromotors exhibit excellent movement performance and biocompatibility, facilitating their in vivo applications and contributing to the advancement of biomedicine.

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice receiving the dual therapy than that of singly treated or untreated mice. It is found that in in vitro the dual therapy increased reactive oxygen stress in treated bacteria. Combination therapy impacted KLP catalase, but not superoxide dismutase (SOD) activity. Finally, alterations in KLP genes encoding 6-phosphogluconate phosphatase or cytochrome C assembly protein are found to be associated with increased resistance to combination gallium therapy, raising the MIC to both Ga(NO₃)₃ and GaPP by 4-fold. These cumulative data lend validation to the potential for the use of Ga(NO₃)₃ and GaPP combination therapy against KLP and suggest that increased oxidative stress is involved in the mechanism of action.

Breast cancer cells exposed to radiotherapy frequently develop radiation resistance through molecular and phenotypic changes. While there is evidences of pathways controlling radioresistance, the evolution of diverse cell phenotypes and transcriptional changes as mediators of radioresistance in breast cancer are restricted. Moreover, the effectiveness of the chemotherapy on radioresistant cells remains uncertain. In this work, an isogenic model of radioresistant breast cancer cells (RR cells) is used to study this phenotype. RR cells show high survival rates after radiation, moreover, RR cells of the triple negative breast cancer (TNBC) subtype show a significantly advanced invasiveness phenotype. Notably, RR cells are significantly sensitive to chemotherapy by inhibit cell survival and promote apoptosis. Transcriptomics and gene co-expression network analysis identify differentially expressed genes (DEGs) and hub genes related to survival and apoptosis pathways in the RR cells of luminal subtype, while in TNBC subtype, cell migration, cell differentiation, and immune pathways are enriched. Hub genes predict the failure of radiotherapy in breast cancer patients, but they are also related to pathological complete response after chemotherapy. Transcriptome changes during acquired radioresistance uncover genes and pathways associated to radio and chemotherapy response. These results demonstrate that radioresistant pathways may converge to develop collateral chemo-sensitivity.

The combination of photoacoustic imaging (PAI) and photothermal therapy (PTT) is an attractive approach in cancer management due to the non-invasive features combined with real-time imaging and selective tissue damage by non-ionizing radiation. This approach is especially appealing for Head and Neck Squamous Cell Carcinoma (HNSCC) management, where up to 40% of patients require modifications of the treatment regimen. On the other hand, most of the agents developed for PAI/PTT suffer from persistence or re-shaping issues. Here, a unique non-persistent plasmon nano-architecture (tNAs-IRDye) is presented that simultaneously acts as a contrast agent for PAI and as a photothermal transducer for PTT. The tNAs-IRDye are fully characterized and evaluated in vitro and ex vivo, and their performance as theranostic agents is assessed in HPV-negative HNSCC murine models. A significant modulation of tumor growth is obtained in vivo upon intratumoral injection of tNAs-IRDye and subsequent NIR irradiation compared to the solely irradiated control. The outcomes of this study exhibit a noteworthy potential to foster the development of innovative clinical strategies for the management of HPV-negative head and neck carcinoma.