Advanced Therapeutics最新文献

Different nanosystems orbiting around the Brain representing future therapies for cerebrovascular and neurodegenerative diseases. Some of these nanosystems are represented in the image: mesoporous silica nanoparticles, liposomes and gold nanoparticles, all of them with encapsulated drugs, to be able to release them in specific regions and treat some brain diseases. More details can be found in article 2400239 by Manuel Desco, María Victoria Gómez-Gaviro, and co-workers. Illustration designed by Celia Martín-Morales.

This image represents a hybrid nanoparticle, dispersed in a thermos-responsive hydrogel, composed of mesoporous silica nanoparticles and liposome-like structure dual-loaded with curcumin and benzydamine hydrochloride for the treatment of vulvovaginal candidiasis. More details can be found in the article by Marlus Chorilli, Hélder A. Santos, and co-workers.

Lipophilic π-conjugated polymers (CPs) encapsulated within self-assembling diblock copolymer poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG–PLGA) nanoparticles, are interesting candidates for photodynamic and photothermal therapies. Upon irradiation, CPs generate reactive oxygen species (ROS), which may either cause local phototoxicity or could be exploited for photodynamic therapy. The propensity of the PEG–PLGA matrix to scavenge ROS has never been investigated. Here the ability of two PEG–PLGA structures (PEG_{2 kDa}–PLGA_{4.5 kDa} vs PEG_{5 kDa}–PLGA_{55 kDa}) to mitigate the release of ROS generated by four different CPs (PFO, F8BT, CN-PPV, and PCPDTBT) following irradiation (5 J cm⁻²) at 385, 455, and 656 nm is studied. The molar content of the PEG–PLGA matrix, rather than the molecular weight or composition, appeared to be the most influential factor, i.e., lower molar concentrations of the matrix polymer are associated with significant increases in phototoxicity. Multivariate analysis reveals that the combination of CP photophysical properties and nanoparticle matrix properties are important for understanding CP nanoparticle-induced phototoxicity.

Impaired bladder compliance secondary to congenital or acquired bladder dysfunction can lead to irreversible kidney damage. This is managed with surgical augmentation utilizing intestinal tissue, which can cause stone formation, infections, and malignant transformation. Co-seeded bone marrow mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSPC) scaffolds (PRS) have been successful in regenerating bladder tissue. However, the acquisition of viable cells is challenging in the clinical setting. Here, the regenerative capacity of human MSC/CD34+ co-cultured total condition media (TCM) is compared to media alone in immune-competent rats augmented with PRS following partial cystectomy. Augmented bladders are instilled with media (control, n = 4) or TCM (n = 5) twice a week for 4 weeks. Regenerated tissue is analyzed for smooth muscle, urothelium, vascular, and peripheral nerve regrowth. Urodynamic (UDS) measures are performed pre- and 4 weeks post-augmentation. The results demonstrate that TCM-instilled grafts have greater muscle content, larger average urothelial widths, higher percent vascularization, and more robust neural infiltration post-augmentation. UDS demonstrates greater percent bladder recovery in the TCM group, indicating functional improvement in bladder storage capacity. This study is the first to propose the use of cell-free TCM as an alternative to traditional cell-seeded scaffolds to promote bladder tissue regeneration.

Autophagy facilitates the degradation and recycling of nonfunctional proteins and organelles in autolysosome, which contributes to tumor maintenance. Antidepressant sertraline was found to induce AMPK-mTOR signaling mediated autophagosome accumulation, but block autophagic flux at the stage of autolysosomal degradation, thus suppressing the colorectal cancer survival. The study reports the repurposing of sertraline as an anticancer drug through the mechanism of inhibiting autophagic flux. More details can be found in article 2400199 by Jiaolin Bao, Ren-Bo Ding and co-workers.

Rheumatoid arthritis (RA) is a complex autoimmune disorder with poorly understood mechanisms. In the article 2400166, Alessandro Polini, Francesca Gervaso, and co-workers introduce a chitosan-based hydrogel for 3D culture of fibroblast-like synoviocytes, offering new insights into RA. The cover image highlights the hydrogel's cellular structure. Cover designed by: Francesco Bisconti, Jacopo Tarantino, Francesca Gervaso, Alessandro Polini.

Mycobacterium leprae infects macrophages and Schwann cells, causing leprosy. Current treatments, though effective, have many side effects. Developing safer therapies, such as drug delivery systems and advances in immunoprophylaxis, can improve efficacy and patient quality of life. More details can be found in article 2400249 by José Lamartine Soares-Sobrinho and co-workers.

Oncolytic viral-delivered chemotherapeutics have exciting potential for metastatic cancer therapies, including colorectal cancer, but require advanced screening systems for better patient prediction. We optimized primary metastatic colorectal tumor processing and 3D (3-dimensional) bioprinted tumors to prove efficacy as long-term screening systems. Normally, this time period would use animals, but we show it is possible to gain useful data in vitro before preclinical stages, to reduce animal modeling and give better clinical trial predictions. Liver tumors were collected from 12 colorectal cancer patients, evaluated for expansion, 3D bioprinted, and tested for ability to create long-term organoid models with screening of oncolytic viral-loaded FCU1 enzyme conversion of 5-fluorocytosine (5-FC) into the highly toxic 5-fluorouracil (5-FU). Donated tumor size was the limiting factor. 75% of patients could be used for screening of viral delivery. Response between patients was overall positive, with good secondary tumor development, outer active cellular content and inner necrotic core. Oncolytic challenge shows good screening potential and cellular targeting, demonstrating an added bystander effect, optimizing the low-dose. Stable long-term metastatic organoid models were made, lasting many months, with potential for retesting rather than one-off analysis. Oncolytic virus-delivered chemotherapy is promising and warrants further investigation for metastatic colorectal cancers.