Development Of Nanomedicines Research Articles

Oral Administration of Bioactive Nanoparticulates for Inflammatory Bowel Disease Therapy by Mitigating Oxidative Stress and Restoring Intestinal Microbiota Homeostasis.

The management of inflammatory bowel disease (IBD) continues to pose significant challenges due to the absence of curative therapies and a high rate of recurrence. Therefore, it is imperative to explore novel approaches to enhance the efficacy of IBD therapy. Herein, a bioactive nanoparticulate s is tailored designed to achieve a "Pull-Push" approach for efficient and safe IBD treatment by integrating reactive oxygen species (ROS) scavenging (Pull) with anti-inflammatory agent delivery (Push) in the inflammatory microenvironment. The multifunctional nanomedicine, designated MON-PAMAM@SASP, is developed through the encapsulation of sulfasalazine (SASP), a widely utilized clinical drug for the treatment of IBD, within cationic diselenide-bridged mesoporous organosilica nanoparticles (MONs) that possess significant antioxidant properties. Herein, poly(amidoamine) (PAMAM) endows the original MONs with positive charge characteristics. The MON-PAMAM@SASP not only displays the remarkable capability of neutralizing ROS to ameliorates intestinal damage, but also achieves controllable release of SASP to mitigate intestinal inflammation. Consequently, this nanomedicine effectively mitigates IBD by colitis in mouse models, and our current research has not identified any significant drug toxicity. Beyond regulating inflammatory microenvironment in intestine, treatment with MON-PAMAM@SASP results in increased richness and restores intestinal microbiota homeostasis, thereby mitigating IBD to a certain extent. Together, our work provides a highly versatile "Pull-Push" approach for IBD management and encourages the development of similar nanomedicine to treating multiple inflammatory diseases of gastrointestinal tract.

The interaction of a self-assembled nanoparticle and a lipid membrane: Binding, disassembly and re-distribution

Here we report a detailed study of the interactions of nanoparticles, formed by the self-assembly of cholesterol-containing porphyrins, with lipid membranes. We show that the interaction is a two-step process: first, the docking and fusion, then, the redistribution of the building blocks of the self-assembled nanoparticles (SANs henceforth). Analysis of the binding and structural data is consistent with the docking step being driven by a multivalence cooperative effect and with the formation of SAN aggregates on the membrane, whilst the solubility of the cholesterol anchor in the membrane is key to both the fusion and redistribution of the SANs building blocks. The tendency of the SAN to aggregate in the membrane helps explain the photosensitizer properties of the SANs, essential to their anti-microbial activity. The solubility of the cholesteryl anchors drives fusion to the membrane and de-assembly of the SAN, explaining the capability of the SANs to deliver therapeutic cargos at the lipid interface. The subsequent redistribution of the SANs building blocks offer a plausible pathway to body clearance that is not immediately available to hard nanoparticles. These properties, and the modularity of the synthesis, point to the SANs being an excellent platform for the development of nanomedicines. An unexpected consequence of unraveling the mechanism of membrane interaction of these SANs is that it allows us to derive a value of the free energy of binding of cholesterol (the membrane anchor of the SAN building blocks) to a lipid membrane, that is consistent with the literature values. This is an additional property that can be exploited to determine the affinity of a variety of membrane anchors to membranes of various compositions.

Advancements in mitochondrial-targeted nanotherapeutics: overcoming biological obstacles and optimizing drug delivery

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology’s role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities.

Multifunctional MnGA Nanozymes for the Treatment of Ulcerative Colitis by Reducing Intestinal Inflammation and Regulating the Intestinal Flora.

In ulcerative colitis (UC), the formation of an inflammatory environment is due to the combined effects of excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), overproduction of proinflammatory cytokines, and disruption of immune system function. There are many kinds of traditional drugs for the clinical treatment of UC, but long-term drug use can cause toxic side effects and drug resistance and can also reduce patient compliance and other drawbacks. Hence, in light of the clinical challenges associated with UC, including the limitations of existing treatments, intense adverse reactions and the development of resistance to medications, no novel therapeutic agents that offer effective relief and maintain a high level of biosafety are urgently needed. Although many anti-inflammatory nanomedicines have been developed by researchers, the development of efficient and nontoxic nanomedicines is still a major challenge in clinical medicine. Using the natural product gallic acid and the metal compound manganese chloride, a highly effective and nontoxic multifunctional nanoenzyme was developed for the treatment of UC. Nanozymes can effectively eliminate ROS and RNS to reduce the inflammation of intestinal epithelial cells caused by oxidation, facilitate the restoration of the intestinal epithelial barrier through the upregulation of tight junction protein expression, and balance the intestinal microbiota to maintain the stability of the intestinal environment. Using a rodent model designed to mimic UC, we monitored body weight, colon length, the spleen index, and the degree of tissue damage and demonstrated that manganese gallate (MnGA) nanoparticles can reduce intestinal inflammation by clearing ROS and active nitrogen. Intestinal flora sequencing revealed that MnGA nanoparticles could regulate the intestinal flora, promote the growth of beneficial bacteria and decrease the levels of detrimental bacteria within the intestinal tract in a mouse model of UC. Thus, MnGA nanoparticles can maintain the balance of the intestinal flora. This study demonstrated that MnGA nanoparticles are excellent antioxidant and effective anti-inflammatory agents, have good biosafety, and can effectively treat UC.

Influence of albumin concentration on surface characteristics and cellular responses in the pre-incubation of multi-walled carbon nanotubes.

Reliable characterization of protein coronas (PCs) that form when nanomaterials are introduced into biological fluids is a critical step in the development of safe and efficient nanomedicine. We observed that bovine serum albumin (BSA)-coated multi-walled carbon nanotubes (MWCNTs) do not induce cytotoxicity, but have different cellular uptake rates depending on the BSA pretreatment concentration. To determine how these slight differences affect A549 cell responses and intracellular changes, we conducted spectroscopic (circular dichroism and Fourier-transform infrared) and spectrometric (nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry) analyses. The various characterization techniques conducted in this study reveal the following. (i) The composition ratio of PCs on MWCNTs differs depending on the BSA concentration. (ii) Analysis of the secondary structure of the proteins revealed that the α-helix structure increased with increasing BSA concentration. (iii) Proteomic analysis showed that different biological pathways were activated at levels higher and lower than 5 mg mL-1. Such combined spectroscopic and spectrometric approaches provide an integrated understanding of PC composition as well as how nano/bio-interface states are linked to cellular-level responses. Our results can support reliable and practical applications of nanomedicine development.

Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.

Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.

Ultra-Small Copper-Based Multienzyme-Like Nanoparticles Protect Against Hepatic Ischemia-Reperfusion Injury Through Scavenging Reactive Oxygen Species in Mice.

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

A nanoprodrug derived from branched poly (ethylene glycol) recognizes prostate-specific membrane antigen to precisely suppress prostate cancer progression

Prostate-specific membrane antigen (PSMA) is overexpressed in 80–90 % of prostate cancers (PCa) and is widely used as a diagnostic and therapeutic biomarker. Docetaxel (DTX), an FDA-approved anti-microtubule drug, is commonly employed to manage metastatic castration-resistant PCa; however, DTX therapy is often associated with severe side effects. One promising strategy to mitigate these side effects is the development of nanomedicine by loading small molecules into biocompatible vectors. Poly (ethylene glycol) (PEG) has been extensively used in clinical settings for this purpose, with PEGylated drugs demonstrating significant success. Compared to linear PEG, branched PEG (multi-arm PEG) provides enhanced stability for nanomedicines. In this study, we developed a novel nanoprodrug 4armPEG-Docetaxel DCL (4armPEG-DD) by conjugating a 4-arm PEG with DTX via a reduction-sensitive disulfide bond and further modifying it with 2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (DCL), a PSMA-targeting ligand. Both in vitro and in vivo results demonstrated that the designed nanoprodrug specifically recognized PSMA-positive PCa cells and effectively released DTX in response to the intracellular reducing environment, leading to potent cytotoxic effects on PSMA-positive prostate tumors. Importantly, 4armPEG-DD exhibited improved in vivo safety compared to small-molecule DTX. Thus, we propose that 4armPEG-DD represents a promising candidate for the clinical treatment of PSMA-positive PCa.

Advances in Drug Delivery Systems for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, and targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, drug resistance, drug side effects, and AML relapse and refractoriness. These intrinsic limitations of current treatments have promoted the development and application of nanomedicine for more effective and safer leukemia therapy. In this review, the classification of nanoparticles applied in AML therapy, including liposomes, polymersomes, micelles, dendrimers, and inorganic nanoparticles, is reviewed. In addition, various strategies for enhancing therapeutic targetability in nanomedicine, including the use of conjugating ligands, biomimetic-nanotechnology, and bone marrow targeting, which indicates the potential to reverse drug resistance, are discussed. The application of nanomedicine for assisting immunotherapy is also involved. Finally, the advantages and possible challenges of nanomedicine for the transition from the preclinical phase to the clinical phase are discussed.

Development of a Simvastatin-Loaded Copolymer Acid-Sensitive Nanocarrier and Its Experimental Use in the Treatment of Keloids.

The lipid-lowering simvastatin (SIM) has been shown to be an effective inhibitor of keloid proliferation. However, due to its low water solubility and short half-life, simvastatin aggregates to the liver and does not reach the skin lesions after oral administration, which restricts its widespread clinical use. The development of nanomedicine provides the possibility for us to break through this bottleneck problem clinically. The objective of this study was to investigate the feasibility of using complex nanocontrolled delivery system (CNDS), simvastatin-loaded polyethylene glycol-poly lactic-co-glycolic acid (PEG-PLGA), in the treatment of keloids. In the invitro study, the release of simvastatin in fibroblasts by CNDS@Simvastatin and its effect on inhibition of the proliferation of fibroblasts, Col Ι, and CTGF by the slow release of simvastatin were assessed. The efficacy of CNDS@Simvastatin in improving keloids and the biocompatibility and safety of CNDS@Simvastatin were examined invivo by establishing a murine ear keloid model. CNDS@Simvastatin showed sustained and uniform inhibition of the proliferation of fibroblasts, Col Ι, and CTGF via the gradual release of simvastatin over 72 h. It was efficient in the treatment of the murine ear keloid with no observable toxic side effects on various organs. Simvastatin-loaded copolymer acid-sensitive nanocarriers, CNDS@Simvastatin nanospheres, were successfully developed in this study, and these were characterized by favorable physicochemical properties and biocompatibility.

Nanoradiosensitizers in glioblastoma treatment: recent advances and future perspectives.

Glioblastoma (GBM), a highly invasive type of brain tumor located within the central nervous system, manifests a median survival time of merely 14.6months. Radiotherapy kills tumor cells through focused high-energy radiation and has become a crucial treatment strategy for GBM, especially in cases where surgical resection is not viable. However, the presence of radioresistant tumor cells limits its clinical effectiveness. Radioresistance is a key factor of treatment failure, prompting the development of various therapeutic strategies to overcome this challenge. With the rapid development of nanomedicine, nanoradiosensitizers provide a novel approach to enhancing the effectiveness of radiotherapy. In this review, we discuss the reasons behind GBM radio-resistance and the mechanisms of radiotherapy sensitization. Then we summarize the primary types of nanoradiosensitizers and recent progress in their application for the radiosensitization of GBM. Finally, we elucidate the factors influencing their practical implementation, along with the challenges and promising prospects associated with multifunctional nanoradiosensitizers.

Titanium Dioxide Nanomaterials: Progress in Synthesis and Application in Drug Delivery.

Background: Recent developments in nanotechnology have provided efficient and promising methods for the treatment of diseases to achieve better therapeutic results and lower side effects. Titanium dioxide (TiO2) nanomaterials are emerging inorganic nanomaterials with excellent properties such as low toxicity and easy functionalization. TiO2 with special nanostructures can be used as delivery vehicles for drugs, genes and antigens for various therapeutic options. The exploration of TiO2-based drug delivery systems shows great promise for translating nanotechnology into clinical applications; Methods: Comprehensive data on titanium dioxide were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration; Results: In this review, we discuss the synthesis pathways and functionalization strategies of TiO2. Recent advances of TiO2 as a drug delivery system, including sustained and controlled drug release delivery systems were introduced. Rigorous long-term systematic toxicity assessment is an extremely critical step in application to the clinic, and toxicity is still a problem that needs to be closely monitored; Conclusions: Despite the great progress made in TiO2-based smart systems, there is still a great potential for development. Future research may focus on developing dual-reaction delivery systems and single-reaction delivery systems like redox and enzyme reactions. Undertaking thorough in vivo investigations is necessary prior to initiating human clinical trials. The high versatility of these smart drug delivery systems will drive the development of novel nanomedicines for personalized treatment and diagnosis of many diseases with poor prognosis.

In Vivo Interactions of Nucleic Acid Nanostructures With Cells.

Nucleic acid nanostructures, derived from the assembly of nucleic acid building blocks (e.g., plasmids and oligonucleotides), are important intracellular carriers of therapeutic cargoes widely utilized in preclinical nanomedicine applications, yet their clinical translation remains scarce. In the era of "translational nucleic acid nanotechnology", a deeper mechanistic understanding of the interactions of nucleic acid nanostructures with cells in vivo will guide the development of more efficacious nanomedicines. This review showcases the recent progress in dissecting the in vivo interactions of four key types of nucleic acid nanostructures (i.e., tile-based, origami, spherical nucleic acid, and nucleic acid nanogel) with cells in rodents over the past five years. Emphasis lies on the cellular-level distribution of nucleic acid nanostructures in various organs and tissues and the cellular responses induced by their cellular entry. Next, in the spirit of preclinical translation, this review features the latest interactions of nucleic acid nanostructures with cells in large animals and humans. Finally, the review offers directions for studying the interactions of nucleic acid nanostructures with cells from both materials and biology perspectives and concludes with some regulatory updates.

Achieving Immune Activation by Suppressing the IDO1 Checkpoint with Sono-Targeted Biobromination for Antitumor Combination Immunotherapy.

Indoleamine-2,3-dioxygenase-1 (IDO1) pathogenically suppresses immune cell infiltration and promotes tumor cell immune escape by overmetabolizing tryptophan to N-formyl kynurenine in the tumor microenvironment (TME). However, it remains challenging for IDO1 immune checkpoint inhibitors to achieve a significant potency of progression-free survival. Here, we developed a breakthrough in IDO1 inhibition by sono-targeted biobromination reaction using immunostimulating hypobromic-P-phenylperoxydibenzoic acid-linked metallic organic framework nanomedicine (H-MOF NM) to remodel the TME from debrominated hypoxia into hypobromated normoxia and activate the IDO1 immune pathway with in vitro and in vivo remarkable antitumor efficacy. H-MOF NM contains Br+ and O- active ingredients with an enlarged band gap to deactivate IDO1 through an innovative biochemical mechanism, taking control over brominating IDO1 amino acid residues at the active sites in the remodeled TME and subsequently activating the immune response, including DC maturation, T-cell activation, and macrophage polarization. Importantly, the H-MOF NM achieves multiple immune responses with high tumor regression potency by combination sono-immunotherapy. This study describes an excellent IDO1 inhibition strategy through the development of immune biobrominative H-MOF nanomedicine and highlights efficient combination immunotherapy for tumor treatment.

Material Trends and Clinical Costings in Systematically Identified CDER‐Approved Nanomedicines

AbstractResearch into mechanisms and potential applications of nanomaterials in medicine has expanded steadily in recent decades, with increasing translational focus. Development costs, including for clinical trials, are often cited as factors limiting the translational viability of novel nanomedicines, especially compared to small new molecular entities (NMEs) and therapeutic biologics. Yet, to date, there has been no systematic investigation into the clinical programs or costs of translating and commercializing nanomedicines, nor a comparison to NMEs and therapeutic biologics, to support these claims. Here, nanomedicines approved by the United States Food and Drug Administration's Center for Drug Evaluation and Research (CDER) from 2011 to 2023 are systematically identified and categorized. Nanomedicines were identified as formulations where submicron particle size contributes to product function. Like biologics and NMEs, nanomedicines are most frequently approved for oncological indications. Notably, all anti‐cancer nanomedicines are indicated to treat orphan diseases, which is representative of the potential for nanomedicines to occupy pharmaceutical niches in treating diseases affecting smaller patient cohorts. The median estimated cost of pivotal trials for nanomedicines is 47% that of biologics and NMEs approved in the same timeframe. The findings indicate higher manufacturing costs in nanomedicine development may be mitigated by savings elsewhere, increasing translational viability.

Antioxidant Carbon Dots Nanozymes Alleviate Stress-induced Depression by Modulating Gut Microbiota.

Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (•OH, O2-•, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.

Atomically Engineered Chlorine Coordination of Iron in Active Centers for Selectively Catalytic H2O2 Decomposition Toward Efficient Antitumor-Specific Therapy.

The intervention of endogenous H2O2 via nanozymes provides a potential antitumor-specific therapy; however, the role of the nanozyme structure in relation to the selective decomposition of H2O2 to hydroxyl radicals (•OH) is yet to be fully understood, which limits the development of this therapeutic approaches. Herein, an iron single-atom nanozyme (Fe─N2Cl2─C SAzyme) is reported, which is prepared through precise Fe─Cl coordination based on the construction of a characteristic Fe-containing molecule. Fe─N2Cl2─C exhibits efficient catalytic H2O2 decomposition (2.19 × 106 mm-1 s-1), which is the highest among reported SAzymes. More importantly, it is found that H2O2 selectively decomposed into •OH on the Fe─N2Cl2─C surface, which is attributable to the d orbitals of the Fe active center matching the O-2p electrons of the adsorbed hydroxide (*OH) intermediate. Fe─N2Cl2─C is strongly cytotoxic toward a variety of cancer-cell lines in vitro but not to normal cells. Furthermore, Fe─N2Cl2─C shows an outstanding specific therapeutic effect in vivo; it efficiently destroys solid malignant tumors without injuring normal tissue. Altogether, these findings highlight the selective catalytic decomposition of H2O2 to •OH, which is achieved by engineering the active center on the atomic level, thereby providing an avenue for the development of specific nanomedicines with efficient antitumor activities.

In‐Silico Nanomedical Exploration of Mefloquine Drug Transport Using Pegylated Graphene Oxide Nanocarrier

AbstractThis study investigates the in‐silico transport of mefloquine (MQ) by using graphene oxide (GO) and polyethylene glycol (PEG)‐functionalized GO nanocarriers. Density functional theory (DFT) calculations are performed to explore the molecular interactions, electronic properties, thermodynamics, and release kinetics of MQ‐GO and MQ‐GO/PEG complexes across different phases and environmental conditions. Results indicate a strong affinity between MQ and both types of nanocarriers, with the adsorption energies ranging from −59.14 to −143.16 kcal mol−1, particularly in acidic environments. This suggests a potential for targeted drug delivery in acidic tumor micro‐environments. The incorporation of PEG, enhances stability and compatibility across phases, with chi interaction parameters of between 1.36 and 28.47, and the energy of mixture values, ranging from 0.80 to 16.86 kcal mol−1. The release time of MQ from the nanocarriers, varies significantly, depending on the adsorption energy, and ranges from 2.03 × 1030 to 6.98 × 1091 milliseconds across different phases, highlighting the need for further optimization of the drug delivery systems. The findings of this study provide valuable insights into the design and development of novel nanomedicines, based on MQ and GO nanocarriers, with implications for malaria treatments.

A singular plasmonic-thermoelectric hollow nanostructure inducing apoptosis and cuproptosis for catalytic cancer therapy

Thermoelectric technology has recently emerged as a distinct therapeutic modality. However, its therapeutic effectiveness is significantly limited by the restricted temperature gradient within living organisms. In this study, we introduce a high-performance plasmonic-thermoelectric catalytic therapy utilizing urchin-like Cu2−xSe hollow nanospheres (HNSs) with a cascade of plasmonic photothermal and thermoelectric conversion processes. Under irradiation by a 1064 nm laser, the plasmonic absorption of Cu2−xSe HNSs, featuring rich copper vacancies (VCu), leads to a rapid localized temperature gradient due to their exceptionally high photothermal conversion efficiency (67.0%). This temperature gradient activates thermoelectric catalysis, generating toxic reactive oxygen species (ROS) targeted at cancer cells. Density functional theory calculations reveal that this vacancy-enhanced thermoelectric catalytic effect arises from a much more carrier concentration and higher electrical conductivity. Furthermore, the exceptional photothermal performance of Cu2−xSe HNSs enhances their peroxidase-like and catalase-like activities, resulting in increased ROS production and apoptosis induction in cancer cells. Here we show that the accumulation of copper ions within cancer cells triggers cuproptosis through toxic mitochondrial protein aggregation, creating a synergistic therapeutic effect. Tumor-bearing female BALB/c mice are used to evaluate the high anti-cancer efficiency. This innovative approach represents the promising instance of plasmonic-thermoelectric catalytic therapy, employing dual pathways (membrane potential reduction and thioctylated protein aggregation) of mitochondrial dysfunction, all achieved within a singular nanostructure. These findings hold significant promise for inspiring the development of energy-converting nanomedicines.

TRPA1-Related Diseases and Applications of Nanotherapy.

Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects.