Advancements and prospects of lipid-based nanoparticles: dual frontiers in cancer treatment and vaccine development.

Cancer is a complex heterogeneous disease that poses a significant public health challenge. In recent years, lipid-based nanoparticles (LBNPs) have expanded drug delivery and vaccine development options owing to their adaptable, non-toxic, tuneable physicochemical properties, versatile surface functionalisation, and biocompatibility. LBNPs are tiny artificial structures composed of lipid-like materials that can be engineered to encapsulate and deliver therapeutic agents with pinpoint accuracy. They have been widely explored in oncology; however, our understanding of their pharmacological mechanisms, effects of their composition, charge, and size on cellular uptake, tumour penetration, and how they can be utilised to develop cancer vaccines is still limited. Hence, we reviewed LBNPs' unique characteristics, biochemical features, and tumour-targeting mechanisms. Furthermore, we examined their ability to enhance cancer therapies and their potential contribution in developing anticancer vaccines. We critically analysed their advantages and challenges impeding swift advancements in oncology and highlighted promising avenues for future research.

LBNPs are tiny artificial particles made of lipids using different formulation methods. They are powerful and versatile delivery platforms with great potential as anticancer therapies. LBNPs have been tested in clinical applications and can safely deliver anticancer agents, including vaccine payloads designed to target various cancer types.LBNPs' size, surface charge, and targeting ligands can be modified during formulation, and they can be administered to specific tissues via various routes. LBNPs can target tumours and release their payload via active, passive, or stimuli-responsive mechanisms.Active targeting requires surface modification in order to target and deliver their payload, while passive targeting do not. Stimuli-responsive release mechanisms move to the tumour microenvironment and release their payload upon an internal or external stimulus.There are several challenges faced by LBNPs in delivering cancer drugs and vaccines, but advanced research methods have opened new doors vital for expanding their applications in clinical oncology.LBNPs offer the advantage of enhanced drug stability and bioavailability, prolonged circulation time of therapeutic agents in the bloodstream, and improved efficacy in targeting cancerous tissues.

Inulin Can Improve Red Blood Cell Cryopreservation by Promoting Vitrification, Stabilizing Cell Membranes, and Inhibiting Ice Recrystallization.

In transfusion medicine, the cryopreservation of red blood cells (RBCs) is of major importance. The organic solvent glycerol (Gly) is considered the current gold-standard cryoprotectant (CPA) for RBC cryopreservation, but the deglycerolization procedure is complex and time-consuming, resulting in severe hemolysis. Therefore, it remains a research hotspot to find biocompatible and effective novel CPAs. Herein, the natural and biocompatible inulin, a polysaccharide, was first employed as a CPA for RBC cryopreservation. The presence of inulin could improve the thawed RBC recovery from 11.83 ± 1.40 to 81.86 ± 0.37%. It was found that inulin could promote vitrification because of its relatively high viscosity and glass transition temperature (Tg'), thus reducing the damage during cryopreservation. Inulin possessed membrane stability, which also had beneficial effects on RBC recovery. Moreover, inulin could inhibit the mechanical damage induced by ice recrystallization during thawing. After cryopreservation, the RBC properties were maintained normally. Mathematical modeling analysis was adopted to compare the performance of inulin, Gly, and hydroxyethyl starch (HES) in cryopreservation, and inulin presented the best efficiency. This work provides a promising CPA for RBC cryopreservation and may be beneficial for transfusion therapy in the clinic.

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.

The obesogenic side of Genistein.

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpß), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.

A tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform for triple-enhanced chemodynamic therapy combined with chemotherapy and H2S therapy.

The high glutathione (GSH) concentration and insufficient H2O2 content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, H2S generation, self-supplied H2O2, co-delivery of doxorubicin (DOX) and Fenton reagent Fe2+ is presented for synergistic triple-enhanced CDT/chemotherapy/H2S therapy. Because the tetrasulfide bond is sensitive to GSH, the nanoplatform can effectively consume GSH, leading to ROS accumulation and H2S generation in the GSH-overexpressed tumor microenvironment. Meanwhile, tetrasulfide bond-induced GSH-depletion triggers the degradation of nanoparticles and the release of DOX and Fe2+. Immediately, Fe2+ catalyzes endogenous H2O2 to highly toxic hydroxyl radicals (˙OH) for CDT, and H2S induces mitochondria injury and causes energy deficiency. Of note, H2S can also decrease the decomposition of H2O2 to augment CDT by downregulating catalase. DOX elicits chemotherapy and promotes H2O2 production to provide a sufficient substrate for enhanced CDT. Importantly, the GSH depletion significantly weakens the scavenging effect on the produced ˙OH, guaranteeing the enhanced and highly efficient CDT. Based on the synergistic effect of triple-augmented CDT, H2S therapy and DOX-mediated chemotherapy, the treatment with this nanoplatform gives rise to a superior antitumor outcome.

Cryopreservation of bioflavonoid-rich plant sources and bioflavonoid-microcapsules: emerging technologies for preserving bioactivity and enhancing nutraceutical applications.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

Starting Editorial of "Cellular Damage: Protection and Induction" Addressing Hot Topics in Cellular Damage, Protection of Cells and Therapy Targeting Bad Cells.

The cell, the fundamental unit of life, is constantly subjected to a myriad of molecular biophysical disturbances [...].

Inhibitory effect of cyclodextrin on Maillard reaction and its mechanism.

Maillard reaction in pharmaceutical preparations refers to a complex chemical reaction existing between reducing excipients and amino-containing drugs in preparations, which can cause a series of quality problems in preparations. Maillard reaction belongs to chemical incompatibility in preparations, and measures should be taken to reduce or avoid it. In this study, the effect of cyclodextrins (commonly used pharmaceutical excipients) on the Maillard reaction and its mechanism in the lysine hydrochloride-lactose solid preparation model were explored for the first time. Our research results show that the embedding of lysine in cyclodextrin can inhibit the Maillard reaction of lysine to some extent, and the embedding of lysine in cyclodextrin with different structures has differences in the inhibitory effects on Maillard reaction.Among the five cyclodextrins we studied, α-CD and HP-ß-CD embedded lysine can reduce Maillard reaction to a greater extent. We suspect that this may be related to the stability of the embedded substance, which needs further study and verification. And our research shows that the inclusion complex between lysine and cyclodextrin may be the result of hydrogen bond, electrostatic attraction, hydrophobic interaction and van der Waals force. Cyclodextrin is expected to solve the problem of Maillard reaction in pharmaceutical industry to some extent.

A cooperation tale of biomolecules and nanomaterials in nanoscale chiral sensing and separation.

The cooperative relationship between biomolecules and nanomaterials makes up a beautiful tale about nanoscale chiral sensing and separation. Biomolecules are considered a fabulous chirality 'donor' to develop chiral sensors and separation systems. Nature has endowed biomolecules with mysterious chirality. Various nanomaterials with specific physicochemical attributes can realize the transmission and amplification of this chirality. We focus on highlighting the advantages of combining biomolecules and nanomaterials in nanoscale chirality. To enhance the sensors' detection sensitivity, novel cooperation approaches between nanomaterials and biomolecules have attracted tremendous attention. Moreover, innovative biomolecule-based nanocomposites possess great importance in developing chiral separation systems with improved assay performance. This review describes the formation of a network based on nanomaterials and biomolecules mainly including DNA, proteins, peptides, amino acids, and polysaccharides. We hope this tale will record the perpetual relation between biomolecules and nanomaterials in nanoscale chirality.

Biophysics in Membrane of Cells.

The membrane of a cell, often compared to a dynamic city border, carries out an intricate dance of controlling entry and exit, guarding the valuable life processes occurring inside [...].

Smart design of a therapeutic nanoplatform for mitochondria-targeted copper-depletion therapy combined with chemotherapy.

Mitochondria-targeted copper-depletion is emerging as an attractive strategy to combat cancer. However, existing copper molecular chelators are non-specific, toxic and ineffective. Here, it is reported that multifunctional nanoparticles (MSN-TPP/BNA-DPA) can not only target mitochondria to deprive copper ions to trigger copper-depletion therapy, but also serve as nanocarriers to deliver anticancer drugs for chemotherapy, which are engineered by conjugating a fluorophore 4-bromo-1,8-naphthalicanhydride (BNA), a copper-depriving moiety dimethylpyridinamine (DPA) and a mitochondrial targeting ligand triphenylphosphonium (TPP) on the surface of mesoporous silica nanoparticles (MSN). BNA and the internal charge transfer of compound BNA-DPA endow MSN-TPP/BNA-DPA with green fluorescence emission upon UV excitation, which can be used to monitor the cellular uptake of nanoparticles. When copper ions bind to DPA, green fluorescence is quenched, providing visualization feedback of copper-depletion. Therapeutically, mitochondria-targeted copper-depletion effectively causes mitochondria damage, elevated oxidative stress and reduced ATP production to induce intensive cancer cell death. Moreover, the mesoporous structure enables MSN-TPP/BNA-DPA to deliver doxorubicin to mitochondria for chemotherapy and enhances copper-depletion therapy through H2O2 production. Together, the synergistic therapeutic effect of enhanced copper-depletion therapy and doxorubicin-mediated chemotherapy achieves a remarkable cancer cell-killing effect and significant tumor growth inhibition in 4T1 tumor-bearing mice. This work provides an efficacious strategy for copper-depletion based synergistic cancer therapy.

Construction of chiral capillary electrochromatography microsystems based on Aspergillus sp. CM96.

Novel chiral capillary electrochromatography (CEC) microsystems were constructed based on Aspergillus sp. CM96. As a newly discovered intrinsic characteristic of the cell, cell chirality occupies an essential position in life evolution. Aspergillus sp. CM96 spore (CM96s) was chosen as a proof of concept to develop chiral capillary columns. Interestingly, various types of amino acid (AA) enantiomers were baseline separated under the optimized conditions. Furthermore, the time-dependent chiral interactions between AAs and CM96s were explored in a wider space. Pectinases generated from Aspergillus sp. CM96 fermentation were immobilized onto graphene oxide-functionalized capillary silica monoliths for separating AA enantiomers. Molecular docking simulations were performed to explore chiral separation mechanisms of pectinase for AA enantiomers. These results indicated that Aspergillus sp. CM96-based CEC microsystems have a significant advantage for chiral separation.

Enhancing bioavailability of natural extracts for nutritional applications through dry powder inhalers (DPI) spray drying: technological advancements and future directions.

Natural ingredients have many applications in modern medicine and pharmaceutical projects. However, they often have low solubility, poor chemical stability, and low bioavailability in vivo. Spray drying technology can overcome these challenges by enhancing the properties of natural ingredients. Moreover, drug delivery systems can be flexibly designed to optimize the performance of natural ingredients. Among the various drug delivery systems, dry powder inhalation (DPI) has attracted much attention in pharmaceutical research. Therefore, this review will focus on the spray drying of natural ingredients for DPI and discuss their synthesis and application.

Cryopreservation of tissues and organs: present, bottlenecks, and future.

Tissue and organ transplantation continues to be an effective measure for saving the lives of certain critically ill patients. The organ preservation methods that are commonly utilized in clinical practice are presently only capable of achieving short-term storage, which is insufficient for meeting the demand for organ transplantation. Ultra-low temperature storage techniques have garnered significant attention due to their capacity for achieving long-term, high-quality preservation of tissues and organs. However, the experience of cryopreserving cells cannot be readily extrapolated to the cryopreservation of complex tissues and organs, and the latter still confronts numerous challenges in its clinical application. This article summarizes the current research progress in the cryogenic preservation of tissues and organs, discusses the limitations of existing studies and the main obstacles facing the cryopreservation of complex tissues and organs, and finally introduces potential directions for future research efforts.

Dimethylglycine Can Enhance the Cryopreservation of Red Blood Cells by Reducing Ice Formation and Oxidative Damage.

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.

Receptors Involved in Mental Disorders and the Use of Clozapine, Chlorpromazine, Olanzapine, and Aripiprazole to Treat Mental Disorders.

Mental illnesses are a global health challenge, and effective medicines are needed to treat these conditions. Psychotropic drugs are commonly prescribed to manage mental disorders, such as schizophrenia, but unfortunately, they can cause significant and undesirable side effects, such as myocarditis, erectile dysfunction, and obesity. Furthermore, some schizophrenic patients may not respond to psychotropic drugs, a condition called schizophrenia-treatment resistance. Fortunately, clozapine is a promising option for patients who exhibit treatment resistance. Unlike chlorpromazine, scientists have found that clozapine has fewer neurological side effects. Additionally, olanzapine and aripiprazole are well-known for their moderating effects on psychosis and are widely used in clinical practice. To further maximize drug efficacy, it is critical to deeply understand the receptors or signaling pathways central to the nervous system, such as serotonin, histamine, trace amines, dopamine, and G-protein coupled receptors. This article provides an overview of the receptors mentioned above, as well as the antipsychotics that interact with them, such as olanzapine, aripiprazole, clozapine, and chlorpromazine. Additionally, this article discusses the general pharmacology of these medications.

Trehalose in Biomedical Cryopreservation-Properties, Mechanisms, Delivery Methods, Applications, Benefits, and Problems.

Cells and tissues are the foundation of translational medicine. At present, one of the main technological obstacles is their preservation for long-term usage while maintaining adequate viability and function. Optimized storage techniques must be developed to make them safer to use in the clinic. Cryopreservation is the most common long-term preservation method to maintain the vitality and function of cells and tissues. But, the formation of ice crystals in cells and tissues is considered to be the main mechanism that could harm cells and tissues during freezing and thawing. To reduce the formation of ice crystals, cryoprotective agents (CPAs) must be added to the cells and tissues to achieve the cryoprotective effect. However, conventional cryopreservation of cells and tissues often needs to use toxic organic solvents as CPAs. As a result, cryopreserved cells and tissues may need to go through a time-consuming washing process to remove CPAs for further applications in translational medicine, and multiple valuable cells are potentially lost or killed. Currently, trehalose has been researched as a nontoxic CPA due to its cryoprotective ability and stability during cryopreservation. Nevertheless, trehalose is a nonpermeable CPA, and the lack of an effective intracellular trehalose delivery method has become the main obstacle to its use in cryopreservation. This article illustrated the properties, mechanisms, delivery methods, and applications of trehalose, summarized the benefits and limits of trehalose, and summed up the findings and research direction of trehalose in biomedical cryopreservation.