Optogenetic mitochondrial preconditioning enhances cardiomyocyte survival under stress.

Mitochondria play a central role in preconditioning-mediated cytoprotection, yet the specific role of mitochondrial membrane potential (ΔΨ) in this process remains incompletely understood. In this study, we employed a next-generation, mitochondrial-targeted optogenetic system (mOpto) to induce precisely controlled (partial and transient) ΔΨ depolarization and investigate its role in enhancing cardiomyocyte resilience to stress. Human AC16 cardiomyocytes expressing mOpto were subjected to low-intensity LED illumination for preconditioning, followed by exposure to stressors including FCCP, HO, or simulated ischemia-reperfusion.

mLumiOpto Is a Mitochondrial-Targeted Gene Therapy for Treating Cancer.

Mitochondria are important in various aspects of cancer development and progression. Targeting mitochondria in cancer cells holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we developed mitochondrial luminoptogenetics (mLumiOpto), an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane potential and induce cancer cell death.

A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous disease that often relapses following treatment with standard radiotherapies and cytotoxic chemotherapies. Combination therapies have potential for treating refractory metastatic TNBC. In this study, we aimed to develop an antibody-drug conjugate with dual payloads (DualADC) as a chemoimmunotherapy for TNBC.

Advanced biomanufacturing and evaluation of adeno-associated virus.

Recombinant adeno-associated virus (rAAV) has been developed as a safe and effective gene delivery vehicle to treat rare genetic diseases. This study aimed to establish a novel biomanufacturing process to achieve high production and purification of various AAV serotypes (AAV2, 5, DJ, DJ8). First, a robust suspensive production process was developed and optimized using Gibco Viral Production Cell 2.

Correction: Chen et al. Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma. 2022, , 130.

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Characterization of the far-red fluorescent probe MitoView 633 for dynamic mitochondrial membrane potential measurement.

MitoView 633, a far-red fluorescent dye, exhibits the ability to accumulate within mitochondria in a membrane potential-dependent manner, as described by the Nernst equation. This characteristic renders it a promising candidate for bioenergetics studies, particularly as a robust indicator of mitochondrial membrane potential (DY). Despite its great potential, its utility in live cell imaging has not been well characterized.

A CD276-Targeted Antibody-Drug Conjugate to Treat Non-Small Lung Cancer (NSCLC).

Non-small cell lung cancer (NSCLC) patients, accounting for approximately 85% of lung cancer cases, are usually diagnosed in advanced stages. Traditional surgical resection and radiotherapy have very limited clinical benefits. The objective of this study was to develop and evaluate a targeted therapy, antibody-drug conjugate (ADC), for NSCLC treatment.

Process improvement of adeno-associated virus (AAV) production.

Adeno-associated viruses (AAVs) have been well characterized and used to deliver therapeutic genes for diseases treatment in clinics and basic research. This study used the triple transient transfection of AAV-DJ/8 as a model expression system to develop and optimize the laboratory production of AAV for research and pre-clinical applications. Specifically, various production parameters, including host cell, transfection reagent, cell density, ratio of plasmid DNA and cells, gene size, and production mode, were tested to determine the optimal process.

Multiscale Modeling of the Mitochondrial Origin of Cardiac Reentrant and Fibrillatory Arrhythmias.

While mitochondrial dysfunction has been implicated in the pathogenesis of cardiac arrhythmias, how the abnormality occurring at the organelle level escalates to influence the rhythm of the heart remains incompletely understood. This is due, in part, to the complexity of the interactions formed by cardiac electrical, mechanical, and metabolic subsystems at various spatiotemporal scales that is difficult to fully comprehend solely with experiments. Computational models have emerged as a powerful tool to explore complicated and highly dynamic biological systems such as the heart, alone or in combination with experimental measurements.

Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers.

Triple-negative breast cancers (TNBCs) are heterogeneous and metastatic, and targeted therapy is highly needed for TNBC treatment. Recent studies showed that extracellular vesicles (EV) have great potential to deliver therapies to treat cancers. This study aimed to develop and evaluate a natural compound, verrucarin A (Ver-A), delivered by targeted EV, to treat TNBC.

Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma.

Glioblastomas, accounting for approximately 50% of gliomas, comprise the most aggressive, highly heterogeneous, and malignant brain tumors. The objective of this study was to develop and evaluate a new targeted therapy, i.e.

Antibody-Drug Conjugate to Treat Meningiomas.

Meningiomas are primary tumors of the central nervous system with high recurrence. It has been reported that somatostatin receptor 2 (SSTR2) is highly expressed in most meningiomas, but there is no effective targeted therapy approved to control meningiomas. This study aimed to develop and evaluate an anti-SSTR2 antibody-drug conjugate (ADC) to target and treat meningiomas.

Investigation into the difference in mitochondrial-cytosolic calcium coupling between adult cardiomyocyte and hiPSC-CM using a novel multifunctional genetic probe.

Ca cycling plays a critical role in regulating cardiomyocyte (CM) function under both physiological and pathological conditions. Mitochondria have been implicated in Ca handling in adult cardiomyocytes (ACMs). However, little is known about their role in the regulation of Ca dynamics in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Dual-Targeted Extracellular Vesicles to Facilitate Combined Therapies for Neuroendocrine Cancer Treatment.

Neuroendocrine (NE) cancers arise from cells within the neuroendocrine system. Chemotherapies and endoradiotherapy have been developed, but their clinical efficacy is limited. The objective of this study was to develop a dual-targeted extracellular vesicles (EV)-delivered combined therapies to treat NE cancer.

Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy.

Neuroendocrine (NE) tumors include a diverse spectrum of hormone-secreting neoplasms that arise from the endocrine and nervous systems. Current chemo- and radio-therapies have marginal curative benefits. The goal of this study was to develop an innovative antibody-drug conjugate (ADC) to effectively treat NE tumors (NETs).

MitoQ regulates redox-related noncoding RNAs to preserve mitochondrial network integrity in pressure-overload heart failure.

Evidence suggests that mitochondrial network integrity is impaired in cardiomyocytes from failing hearts. While oxidative stress has been implicated in heart failure (HF)-associated mitochondrial remodeling, the effect of mitochondrial-targeted antioxidants, such as mitoquinone (MitoQ), on the mitochondrial network in a model of HF (e.g.

Targeted Exosomes for Drug Delivery: Biomanufacturing, Surface Tagging, and Validation.

Exosomes hold great potential to deliver therapeutic reagents for cancer treatment due to its inherent low antigenicity. However, several technical barriers, such as low productivity and ineffective cancer targeting, need to be overcome before wide clinical applications. The present study aims at creating a new biomanufacturing platform of cancer-targeted exosomes for drug delivery.

Novel biomanufacturing platform for large-scale and high-quality human T cells production.

The adoptive transfer of human T cells or genetically-engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. The objective of this study was to develop a novel T cell biomanufacturing platform using stirred-tank bioreactor for large-scale and high-quality cellular production. First, various factors, such as bioreactor parameters, media, supplements, stimulation, seed age, and donors, were investigated.