Cubic Phase-Inducible Zwitterionic Phospholipids Improve the Functional Delivery of mRNA.

Lipid nanoparticles (LNPs) are clinically advanced delivery systems for RNA. The extensively developed structure of ionizable lipids greatly contributes to the functional delivery of mRNA. However, endosomal escape is one of the severe biological barriers that continue to render this process inefficient (e.

Different Effects of Berberine Delivery to Mitochondria on Cells Derived from the Neural Crest.

Energy metabolism is crucial for cell polarity and pathogenesis. Mitochondria, which are essential for maintaining energy homeostasis within cells, can be targeted by drug delivery to regulate energy metabolism. However, there is a lack of research comparing how mitochondria control energy metabolism in different cell types derived from the neural crest.

Activation of Mitochondria in Mesenchymal Stem Cells by Mitochondrial Delivery of Coenzyme Q.

The efficacy of mesenchymal stem cell (MSC) transplantation has been reported for various diseases. We previously developed a drug delivery system targeting mitochondria (MITO-Porter) by using a microfluidic device to encapsulate Coenzyme Q (CoQ) on a large scale. The current study aimed to confirm if treatment with CoQ encapsulated by MITO-Porter enhanced mitochondrial functions in MSCs, with the potential to improve MSC transplantation therapy.

The impact of, and expectations for, lipid nanoparticle technology: From cellular targeting to organelle targeting.

The success of mRNA vaccines against COVID-19 has enhanced the potential of lipid nanoparticles (LNPs) as a system for the delivery of mRNA. In this review, we describe our progress using a lipid library to engineer ionizable lipids and promote LNP technology from the viewpoints of safety, controlled biodistribution, and mRNA vaccines. These advancements in LNP technology are applied to cancer immunology, and a potential nano-DDS is constructed to evaluate immune status that is associated with a cancer-immunity cycle that includes the sub-cycles in tumor microenvironments.

Investigation of the Nanoparticulation Method and Cell-Killing Effect following the Mitochondrial Delivery of Hydrophobic Porphyrin-Based Photosensitizers.

Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating the photosensitizer rTPA into MITO-Porter (MP), a mitochondria-targeted Drug Delivery System (DDS), aimed at mitochondrial delivery of the photosensitizer while maintaining its activity. In this study, we report the results of our studies to alleviate rTPA aggregation in an effort to improve drug efficacy and assess the usefulness of modifying the rTPA side chain to improve the mitochondrial retention of MITO-Porter, which exhibits high therapeutic efficacy.

Activation of Mitochondrial Oxygen Consumption Rate by Delivering Coenzyme Q to Mitochondria of Rat Skeletal Muscle Cell (L6).

Numerous mitochondria are present in skeletal muscle cells. Muscle disease and aging impair mitochondrial functioning in the skeletal muscle. However, there have been few reports of therapeutic intervention via drug delivery to mitochondria owing to methodological difficulties.

Human cardiosphere-derived cells with activated mitochondria for better myocardial regenerative therapy.

Cell transplantation is a promising therapeutic strategy for myocardial regeneration therapy. To improve therapeutic effects, we developed a culture medium additive that enhances the mitochondrial function of cardiomyocytes for transplantation. A mitochondrial targeting drug delivery system (MITO-Porter system) was used to deliver mitochondrial activation molecules to mouse-derived cardiac progenitor cells.

Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons.

Most of the energy in neurons is produced in mitochondria. Mitochondria generate the ATP that is essential for neuronal growth, function, and regeneration. Mitochondrial axonal transport plays a crucial role in maintaining neuronal homeostasis and biological activity.

Differences in the Intracellular Localization of Methylated β-Cyclodextrins-Threaded Polyrotaxanes Lead to Different Cellular States.

Activation of autophagy represents a potential therapeutic strategy for the treatment of diseases that are caused by the accumulation of defective proteins and the formation of abnormal organelles. Methylated β-cyclodextrins-threaded polyrotaxane (Me-PRX), a supramolecular structured polymer, induces autophagy by interacting with the endoplasmic reticulum. We previously reported on the successful activation of mitochondria-targeted autophagy by delivering Me-RRX to mitochondria using a MITO-Porter, a mitochondria-targeted nanocarrier.

Development of light-induced disruptive liposomes (LiDL) as a photoswitchable carrier for intracellular substance delivery.

Light-driven inward proton pump rhodopsin XeR was embedded in pH-sensitive liposomes. Substance release from the proteoliposomes was observed following light illumination both and in cells, indicating the successful production of light-induced disruptive liposomes (LiDL). Thus, LiDL is a photoswitchable carrier utilized for intracellular substance delivery.

A system that delivers an antioxidant to mitochondria for the treatment of drug-induced liver injury.

Mitochondria, a major source of reactive oxygen species (ROS), are intimately involved in the response to oxidative stress in the body. The production of excessive ROS affects the balance between oxidative responses and antioxidant defense mechanisms thus perturbing mitochondrial function eventually leading to tissue injury. Therefore, antioxidant therapies that target mitochondria can be used to treat such diseases and improve general health.

RNA Delivery to Mitochondria.

The approval of mRNA-containing lipid nanoparticles (LNPs) for use in a vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the clinical utility of RNA-loaded nanocapsules has stimulated a rapid acceleration in research in this area. The development of mRNA-containing LNP vaccines has been rapid, not only because of regulatory adjustments, but also to the advances made in nucleic acid delivery as the result of efforts by many basic researchers. RNA functions, not only in the nucleus and cytoplasm, but also in mitochondria, which have their own genomic apparatus.

Monocarboxylate transporter 4 involves in energy metabolism and drug sensitivity in hypoxia.

Metabolic reprogramming of cancer cells is a potential target for cancer therapy. It is also known that a hypoxic environment, one of the tumor microenvironments, can alter the energy metabolism from oxidative phosphorylation to glycolysis. However, the relationship between hypoxia and drug sensitivity, which targets energy metabolism, is not well known.

Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine.

Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation of intracellular metabolism. Therefore, BBR has attracted considerable interest as a possible therapeutic drug for neurodegenerative diseases.

An effective mitochondria-targeting nanocarrier combined with a π-extended porphyrin-type photosensitizer.

A photochemical reaction mediated by light-activated molecules (photosensitizers) in photodynamic therapy (PDT) causes molecular oxygen to be converted into highly reactive oxygen species (ROS) that are beneficial for cancer therapy. As the active oxygen consumer and the primary regulator of apoptosis, mitochondria are known as an important target for optimizing PDT outcomes. However, most of the clinically used photosensitizers exhibited a poor tumor accumulation profile as well as lack of mitochondria targeting ability.

Fine-tuning the encapsulation of a photosensitizer in nanoparticles reveals the relationship between internal structure and phototherapeutic effects.

Photodynamic therapy (PDT) is a cancer therapy that uses a photosensitizer (PS) in the presence of oxygen molecules. Since singlet oxygen is highly reactive, it is important to deliver it to the target site. Thus, an efficient drug delivery system (DDS) is essential for enhancing the efficacy of such a treatment and protecting against the side effects of PDT.

Extrahepatic targeting of lipid nanoparticles in vivo with intracellular targeting for future nanomedicines.

A new era of nanomedicines that involve nucleic acids/gene therapy has been opened after two decades in 21st century and new types of more efficient drug delivery systems (DDS) are highly expected and will include extrahepatic delivery. In this review, we summarize the possibility and expectations for the extrahepatic delivery of small interfering RNA/messenger RNA/plasmid DNA/genome editing to the spleen, lung, tumor, lymph nodes as well as the liver based on our studies as well as reported information. Passive targeting and active targeting are discussed in in vivo delivery and the importance of controlled intracellular trafficking for successful therapeutic results are also discussed.

Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification.

Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats.

[Development of an Online Role-play-based Medical Interview Training Method for Fourth-year Pharmacy Students].

With the coronavirus disease 2019 pandemic, businesses are rapidly expanding their online practices, and the online medical care system has been established and is growing. The field of pharmacy education is also looking for ways to conduct practical online training. Hence, we developed an online role-play-based medical interview training method for fourth-year pharmacy students.

Innovative cancer nanomedicine based on immunology, gene editing, intracellular trafficking control.

The recent rapid progress in the area of drug delivery systems (DDS) has opened a new era in medicine with a strong linkage to understanding the molecular mechanisms associated with cancer survival. In this review, we summarize new cancer strategies that have recently been developed based on our DDS technology. Cancer immunotherapy will be improved based on the concept of the cancer immunity cycle, which focuses on dynamic interactions between various types of cancer and immune cells in our body.

Recent advances in delivering RNA-based therapeutics to mitochondria.

Introduction: After the emergence of lipid nanoparticles (LNP) containing therapeutic mRNA as vaccines for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the clinical usefulness of nucleic acid-encapsulated LNPs is now a fact. In addition to the nucleus and cytoplasm, mitochondria, which have their own genome, are a site where nucleic acids function in the cell. Gene therapies targeting mitochondria are expected to pave the way for the next generation of therapies.

Transplantation of MITO cells, mitochondria activated cardiac progenitor cells, to the ischemic myocardium of mouse enhances the therapeutic effect.

Given the potential for myocardial stem cell transplantation as a promising treatment for heart failure, numerous clinical trials have been conducted and its usefulness has been clearly confirmed. However, the low rate of engraftment of transplanted cells has become a clinical problem, and this needs to be improved in the case of transplanting cells to the heart. To address this issue, we report on attempts to prepare mitochondria-activated stem cells (MITO cells) for use in transplantation.

Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells.

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells).

Validation of the Mitochondrial Delivery of Vitamin B to Enhance ATP Production Using SH-SY5Y Cells, a Model Neuroblast.

Large amounts of ATP are produced in mitochondria especially in the brain and heart, where energy consumption is high compared with other organs. Thus, a decrease in ATP production in such organs could be a cause of many diseases such as neurodegenerative diseases and heart disease. Based on thus assumption, increasing intracellular ATP production in such organs could be a therapeutic strategy.

Targeting the Mitochondrial Genome Via a MITO-Porter : Evaluation of mtDNA and mtRNA Levels and Mitochondrial Function.

Genetic mutations and defects in mitochondrial DNA (mtDNA) are associated with certain types of mitochondrial dysfunctions, ultimately resulting in the emergence of a variety of human diseases. To achieve an effective mitochondrial gene therapy, it will be necessary to deliver therapeutic agents to the innermost mitochondrial space (the mitochondrial matrix), which contains the mtDNA pool. We recently developed a MITO-Porter, a liposome-based nanocarrier that delivers cargo to mitochondria via a membrane-fusion mechanism.