intercellular communication, maintaining cellular and systematic homeostasis, and antigen-specific T-and B cell responses. This critical review summarizes the advancement of exosome based vaccine development and delivery, and this comprehensive review can be used as a valuable reference for the broader delivery science community.

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Excessive body fat and high cholesterol are one of the leading reasons for triggering cardiovascular risk factors, obesity, and type 2 diabetes. Beta-glucan (BG)-based dietary fibers are found to be effective for lowering fat digestion in the gastrointestinal tract. However, the fat capturing mechanism of BG in aqueous medium is still elusive. In this report, we studied the dietary effect of barley-extracted BG on docosahexaenoic acid (DHA, a model fat molecule) uptake and the impact of the aqueous medium on their interactions using computational modeling and experimental parameters. The possible microscale and macroscale molecular interactions between BG and DHA in an aqueous medium were analyzed through density functional theory (DFT), Monte-Carlo (MC), and molecular dynamics (MD) simulations. DFT analysis revealed that the BG polymer extends hydrogen bonding and nonbonding interactions with DHA. Bulk simulation with multiple DHA molecules on a long-chain BG showed that a viscous colloidal system is formed upon increasing DHA loading. Experimental size and zeta potential measurements also confirmed the electrostatic interaction between BG−DHA systems. Furthermore, simulated and experimental diffusion and viscosity measurements showed excellent agreement. These simulated and experimental results revealed the mechanistic pathway of how BG fibers form colloidal systems with fat molecules, which is probably responsible for BG-induced delayed fat digestion and further halting of fatty molecule absorption in the GI tract.

Chemotherapy-induced cardiac toxicity is an undesirable yet very common effect that increases the risk of death and reduce the quality of life of individuals undergoing chemotherapy. However, no feasible methods and techniques are available to monitor and detect the degree of cardiotoxicity at an early stage. Therefore, in this project, we aim to develop a fluorescent nanoprobe to image the toxicity within the cardiac tissue induced by an anticancer drug. We have observed that vascular cell adhesion molecule 1 (VCAM1) protein alone with collagen was overly expressed within the heart, when an animal was treated with doxorubicin (DOX), because of inflammation in the epithelial cells. We hypothesize that developing a VCAM1-targeted peptide-based (VHPKQHRGGSKGC) fluorescent nanoprobe can detect and visualize the affected heart. In this regard, we prepared a poly­(lactic-co-glycolic acid) (PLGA) nanoparticle linked with VCAM1 peptide and rhodamine B (PLGA–VCAM1–RhB). Selective binding and higher accumulation of the PLGA–VCAM1–RhB nanoprobes were detected in DOX-treated human cardiomyocyte cells (HCMs) compared to the untreated cells. For in vivo studies, DOX (5 mg/kg) was injected via the tail vein once in two weeks for 6 weeks (3 injection total). PLGA–VCAM1–RhB and PLGA–RhB were injected via the tail vein after 1 week of the last dose of DOX, and images were taken 4 h after administration. A higher fluorescent signal of PLGA–RhB–VCAM-1 (48.62% ± 12.79%) was observed in DOX-treated animals compared to the untreated control PLGA–RhB (10.61% ± 4.90) within the heart, indicating the specificity and targeting ability of PLGA–VCAM1–RhB to the inflamed tissues. The quantified fluorescence intensity of the homogenized cardiac tissue of PLGA–RhB–VCAM1 showed 156% higher intensity than the healthy control group. We conclude that PLGA–VCAM1–RhB has the potential to bind inflamed cardiac cells, thereby detecting DOX-induced cardiotoxicity and damaged heart at an early stage.

Pathological fibrosis is distinguished from physiological wound healing by persistent myofibroblast activation, suggesting that therapies that induce myofibroblast apoptosis selectively could prevent progression and potentially reverse the established fibrosis, such as for scleroderma (a heterogeneous autoimmune disease characterized by multiorgan fibrosis). Navitoclax (NAVI) is a BCL-2/BCL-xL inhibitor with antifibrotic properties and has been investigated as a potential therapeutic for fibrosis. NAVI makes myofibroblasts particularly vulnerable to apoptosis. However, despite NAVI's significant potency, clinical translation of BCL-2 inhibitors, NAVI in this case, is hindered due to the risk of thrombocytopenia. Therefore, in this work, we utilized a newly developed ionic liquid formulation of NAVI for direct topical application to the skin, thereby avoiding systemic circulation and off-targetmediated side effects. The ionic liquid composed of choline and octanoic acid (COA) at a 1:2 molar ionic ratio increases skin diffusion and transportation of NAVI and maintains their retention within the dermis for a prolonged duration. Topical administration of NAVI-mediated BCL-xL and BCL-2 inhibition results in the transition of myofibroblast to fibroblast and ameliorates pre-existing fibrosis, as demonstrated in a scleroderma mouse model. We have observed a significant reduction of α-SMA and collagen, which are known as fibrosis marker proteins, as a result of the inhibition of antiapoptotic proteins BCL-2/BCL-xL. Overall, our findings show that COA-assisted topical delivery of NAVI upregulates apoptosis specific to myofibroblasts, with minimal presence of the drug in the systemic circulation, resulting in an accelerated therapeutic effect with no discernible drug-associated toxicity.