Search

PurposeThere is a growing interest in extracellular vesicles (EVs) for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactor cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs.MethodsThe morphology and nanomechanical properties of retinal organoid EVs were assessed using Nanoparticle tracking analysis (NTA) and Atomic force microscopy (AFM). Gene expression analysis of exosome biogenesis of early and late retinal organoids were compared using qPCR. The protein profile of the EVs were analyzed with proteomic tools.ResultsNTA indicated the average size of EV as 100-250 nm. A high expression of exosome biogenesis genes was observed in late retinal organoids EVs. Immunoblot analysis showed highly expressed exosomal markers in late retinal organoids EVs compared to early retinal organoids EVs. Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders.ConclusionThis study provides supplementary knowledge on the properties of retinal organoid EVs and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.

Dicarboxylate metallosurfactants (AASM), synthesized by mixing N‐dodecyl aminomalonate, ‐aspartate and ‐glutamate with CaCl2, MnCl2 and CdCl2, were characterized by XRD, FTIR, and NMR spectroscopy. Layered structures, formed by metallosurfactants, were evidenced from differential scanning calorimetry and thermogravimetric analyses. Solvent‐spread monolayer of AASM in combination with soyphosphatidylcholine (SPC) and cholesterol (CHOL) were studied using Langmuir surface balance. With increasing mole fraction of AASM mean molecular area increased and passed through maxima at ~60 mol% of AASMs, indicating molecular packing reorganization. Systems with 20 and 60 mol% AASM exhibited positive deviations from ideal behavior signifying repulsive interaction between the AASM and SPC, while synergistic interactions were established from the negative deviation at other combinations. Dynamic surface elasticity increased with increasing surface pressure signifying formation of rigid monolayer. Transition of monolayer from gaseous to liquid expanded to liquid condensed state was established by Brewster angle microscopic studies. Stability of the hybrid vesicles, formed by AASM+SPC+CHOL, were established by monitoring their size, zeta potential and polydispersity index values over 100 days. Size and spherical morphology of hybrid vesicles were confirmed by transmission electron microscopic studies. Biocompatibility of the hybrid vesicles were established by cytotoxicity studies revealing their possible applications in drug delivery and imaging. [ABSTRACT FROM AUTHOR]

Herein, we report the metal ion sensing property of two 2,2'‐bis (pyridylmethyl) amine‐based chromogenic probes at physiological pH in buffered media. The binding of metal ions to the bispicolyl site alters its electronic property, which subsequently influences the optical property of the covalently‐linked signaling unit. The compound experienced a change in the solution color from red to deep and light yellow respectively upon the addition of Cu2+ and Ni2+ ions. Further, it is observed that by modifying the signaling unit, one can tune the mode of metal ion binding and sensitivity. The compound with an electron‐deficient quinolinium unit as the signaling moiety, showed 2 : 1 stoichiometry of binding with metal ions, while the compound functionalized with a pyrene unit formed complexes with 1 : 1 stoichiometry. It was conferred that changes in the signaling moiety not only alter the basicity/nucleophilicity of the pyridine nitrogen ends but also influence their aggregation properties. Such kind of studies will be beneficial for engineering new optical probes with tuneable sensitivity. [ABSTRACT FROM AUTHOR]

The human world has been plagued with different kinds of bacterial infections from time immemorial. The increased development of resistance towards commercial antibiotics has made these bacterial infections an even more critical challenge. Bacteria have modified their mode of interactions with different types of commercial drugs by bringing changes to the receptor proteins or by other resisting mechanisms like drug efflux. Various chemical approaches have been made to date to fight against these smart adapting species. Towards this, we hypothesize chemically modifying the commercial antibacterial drugs in order to deceive the bacteria and destroy the bacterial biomass. In this study, different molecular weight polyethyleneimines are taken and conjugated with some well-known commercial drugs like penicillin and chloramphenicol to explore their antibacterial properties against some of the laboratory and uro-pathogenic strains of Gram-positive and Gram-negative bacteria. A detailed structure–activity relationship of these polymeric prodrug-like materials has been evaluated to determine the optimum formulation. The standardized system not only shows significant ∼90% bacterial killing in liquid broth culture, but also demonstrates promising bacterial inhibition towards biofilm formation for the pathogenic strains on inanimate surfaces like urinary catheters and on an in vivo mouse skin abrasion model. The reported bioactive polymeric materials can be successfully used for widespread therapeutic applications with promising medical relevance. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in the fundamental scientific understanding of GBM is swiftly translated into more advanced stages of therapeutic studies. Despite extensive efforts to identify new therapeutic approaches, GBM exhibits a high mortality rate. The current efficacy of treatments for GBM patients is insufficient due to factors such as tumor heterogeneity, the blood–brain barrier, glioma stem cells, drug efflux pumps, and DNA damage repair mechanisms. Considering this, pharmacological cocktail therapy has demonstrated a growing efficacy in addressing these challenges. Towards this, various forms of immunotherapy, including the immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have emerged as potential strategies for enhancing the prognosis of GBM. Current investigations are focused on exploring combination therapies to mitigate undesirable side effects and enhance immune responses against tumors. Furthermore, clinical trials are underway to evaluate the efficacy of several strategies to circumvent the blood–brain barrier (BBB) to achieve targeted delivery in patients suffering from recurrent GBM. In this review, we have described the biological and molecular targets for GBM therapy, pharmacologic therapy status, prominent resistance mechanisms, and new treatment approaches. We also discuss these promising therapeutic approaches to assess prospective innovative therapeutic agents and evaluated the present state of preclinical and clinical studies in GBM treatment. Overall, this review attempts to provide comprehensive information on the current status of GBM therapy. [ABSTRACT FROM AUTHOR]