Bioengineering & Translational Medicine最新文献

Zhang C, Song J, Lou L, et al. Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma. Bioeng Transl Med 2020;6(3):e10203.

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Polymeric micro- and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine-delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin-12 (IL-12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic-aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL-12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL-12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL-12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL-12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL-12 and sufficient time is allowed for albumin-hIL-12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate-buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.

Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth. Currently, a considerable amount of research is focused on discovering new drug molecules to combat the existing research gap in epigenetic drug therapy. A novel and efficient delivery system can be established as a promising approach to overcome the drawbacks associated with the current epigenetic modulators. Therefore, formulating the existing epigenetic drugs with distinct encapsulation strategies in nanocarriers, including solid lipid nanoparticles, nanogels, bio-engineered nanocarriers, liposomes, surface modified nanoparticles, and polymer–drug conjugates have been examined for therapeutic efficacy. Nonetheless, several epigenetic modulators are untouched for their therapeutic potential through different delivery strategies. This review provides a comprehensive up to date discussion on the research findings of various epigenetics mechanism, epigenetic modulators, and delivery strategies utilized to improve their therapeutic outcome. Furthermore, this review also highlights the recently emerged CRISPR tool for epigenome editing.

The endometrium, the inner lining of the uterus, assumes a crucial role in the female reproductive system. Disorders and injuries impacting the endometrium can lead to profound consequences, including infertility and compromised women's overall health. Recent advancements in stem cell research have opened new possibilities for the treatment and repair of endometrial issues. In the present study, we constructed a degradable hydrogel by loading adipose-derived stem cells (ADSCs) and melanin nanoparticles (MNP). In vitro cell experiments validated the biocompatibility of the prepared hydrogels and their adeptness in encapsulating ADSCs. Subsequently, we explored the impact of hydrogel@ADSC@MNP constructs in the healing process of uterine injury in mice. The results indicated that hydrogel@ADSC@MNP could augment endometrial thickness and ameliorate endometrial interstitial fibrosis. The injured tissue adjacent to hydrogel@ADSC@MNP constructs exhibited higher levels of bFGF, IGF-1, and VEGFA compared with the corresponding tissue in mice receiving hydrogel constructs alone or in the model group. Furthermore, the hydrogel@ADSC@MNP system enhanced the proliferative capabilities of uterine endometrial cells, facilitated microvasculature regeneration, and reinstated the endometrium's capacity to receive the embryos. Our findings strongly suggest that the hydrogel@ADSC@MNP system holds significant promise for repairing and regenerating damaged endometrium.

Chao Deng, Qiong Liu, Huadong Zhao, Lu Qian, Wagnrui Lei, Wenwen Yang, Zhenxing Liang, Ye Tian, Shaofei Zhang, Changyu Wang, Ying Chen, Yang Yang. Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome. Bioeng Transl Med. 2023; 8(3):e10517.

An inaccuracy has been found in the statistical graph of ABCA1 in Figure 2c of the published article. The corrected version of Figure 2 is shown below.

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The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD-based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD-based mRNA vaccines encoding binding receptor-binding domain (RBD) of SARS-CoV-2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil-based immunotherapies and their clinical potential.