Future Nanomedicine Research Articles

Biomimetic Single-Atom Nanozyme for Dual Starvation-Enhanced Breast Cancer Immunotherapy.

Cold exposure (CE) therapy is an innovative and cost-efficient cancer treatment that activates brown adipose tissue to compete for glucose uptake, leading to metabolic starvation in tumors. Exploring the combined antitumor mechanisms of CE and traditional therapies (such as nanocatalysis) is exciting and promising. In this study, a platelet membrane biomimetic single-atom nanozyme (SAEs) nanodrug (PFB) carrying bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES) is developed for use in cancer CE therapy. Owing to the platelet membrane modification, PFB can effectively target tumors. Upon entering cancer cells, the dual starvation effect induced by CE treatment and BPTES can significantly diminish intracellular glucose and ATP levels, resulting in a substantial reduction in cellular (glutathione) GSH, which can enhance the cytotoxic efficacy of reactive oxygen species generated by SAEs. This strategy not only boosts ROS production in tumors, but also strengthens immune responses, particularly by increasing memory T-cell abundance and suppressing distant tumor growth and tumor metastasis. Compared with SAEs therapy alone, this combined approach offers superior benefits for tumor immunotherapy. This study achieves a combination of CE and nanomedicines for the first time, providing new ideas for future nanomedicine combination therapy modalities.

Tailoring metal oxide nanozymes for biomedical applications: trends, limitations, and perceptions.

Nanomaterials with enzyme-like properties are known as 'nanozymes'. Nanozymes are preferred over natural enzymes due to their nanoscale characteristics and ease of tailoring of their physicochemical properties such as size, structure, composition, surface chemistry, crystal planes, oxygen vacancy, and surface valence state. Interestingly, nanozymes can be precisely controlled to improve their catalytic ability, stability, and specificity which is unattainable by natural enzymes. Therefore, tailor-made nanozymes are being favored over natural enzymes for a range of potential applications and better prospects. In this context, metal oxide nanoparticles with nanozyme-mimicking characteristics are exclusively being used in biomedical sectors and opening new avenues for future nanomedicine. Realising the importance of this emerging area, here, we discuss the mechanistic actions of metal oxide nanozymes along with their key characteristics which affect their enzymatic actions. Further, in this critical review, the recent progress towards the development of point-of-care (POC) diagnostic devices, cancer therapy, drug delivery, advanced antimicrobials/antibiofilm, dental caries, neurodegenerative diseases, and wound healing potential of metal oxide nanozymes is deliberated. The advantages of employing metal oxide nanozymes, their potential limitations in terms of nanotoxicity, and possible prospects for biomedical applications are also discussed with future recommendations.

The challenge and opportunity of gut microbiota-targeted nanomedicine for colorectal cancer therapy.

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management.

Nanomedicines: Nano based Drug Delivery Systems Challenges and Future of nanomedicines

Over the past ten years, the research and delivery of drugs has emerged as a rapidly expanding, highly capital-intensive, and demanding industry. This procedure is costly and time-consuming, and it has to deal with issues with rapid excretion, degradability, toxicity, low efficacy, biocompatibility, and low bioavailability. Nanomaterial are superior to conventional drug because they have remarkable qualities such as a high invasion rate, regulated, targeted, and gradual drug release, as well as easy receptor accessibility. Despite all of its importance, one of the main issues with different nanoparticles utilized as medication delivery systems is their toxicity. This review discusses the issue surrounding conventional drugs, the importance of nanomedicines in medication administration, and their potential for toxicity and also their future aspect that helps to improve health.

An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo

The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.

Living cells and biological mechanisms as prototypes for developing chemical artificial intelligence

Artificial Intelligence (AI) is having a revolutionary impact on our societies. It is helping humans in facing the global challenges of this century. Traditionally, AI is developed in software or through neuromorphic engineering in hardware. More recently, a brand-new strategy has been proposed. It is the so-called Chemical AI (CAI), which exploits molecular, supramolecular, and systems chemistry in wetware to mimic human intelligence. In this work, two promising approaches for boosting CAI are described. One regards designing and implementing neural surrogates that can communicate through optical or chemical signals and give rise to networks for computational purposes and to develop micro/nanorobotics. The other approach concerns “bottom-up synthetic cells” that can be exploited for applications in various scenarios, including future nano-medicine. Both topics are presented at a basic level, mainly to inform the broader audience of non-specialists, and so favour the rise of interest in these frontier subjects.

Exploring the In Vitro Antidiabetic Potential of Metal Oxide Nanoparticles Synthesized Using Lemongrass and Mint Formulation.

Aim This study aimed to compare the antidiabetic effect of metal oxide nanoparticles (CuONPs and ZnONPs)prepared using lemongrass and mint herbal formulations. Introduction The study explores green-synthesized nanoparticles for potential applications in diabetes management, emphasizing sustainable synthesis methods, particularly zinc oxide nanoparticles (ZnONPs) and copper oxide nanoparticles (CuONPs) produced from lemongrass and mint herbal formulations. The study was prompted by the increasing importance of innovative therapeutic strategies, responding to emerging health challenges, and leveraging advancements in nanotechnology and eco-friendly practices to explore the potential of green-synthesized nanoparticles in diabetes management. Methods The methods involve herbal formulation preparation, CuONPs and ZnONPs synthesis, and UV-visible spectrophotometry for characterization. In vitro antidiabetic activity is assessed through α-amylase and β-glucosidase enzyme assays using varied nanoparticle concentrations (10-50 µL). Results Visual observations confirm successful synthesis, with distinct color changes observed in both CuONPs and ZnONPs after 24 hours. UV-visible spectrophotometry reveals absorption peaks at 440 nm and 380 nm for CuONPs and ZnONPs, respectively. In the α-amylase assay, both nanoparticles exhibit concentration-dependent inhibition, with CuONPs ranging from 40% to 77% and ZnONPs ranging from 36% to 80%. The β-glucosidase assay demonstrates similar concentration-dependent inhibition patterns, highlighting significant differences. Conclusion The study concludes that CuONPs and ZnONPs synthesis using lemongrass and mint herbal formulations show concentration-dependent antidiabetic activity. The comparative analysis underscores the need for tailored approaches based on nanoparticle composition. These findings contribute valuable insights into the therapeutic potential of green-synthesized nanoparticles, paving the way for future nanomedicine research and development in diabetes management.

Green synthesis of silver nanoparticles using Justicia adhatoda leaves extract and its anticancer effect on human lung carcinoma via induced apoptosis mechanism

In this study, Justicia adhatoda leaves extract was used to synthesize silver nanoparticles (AgNPs) and assess its anticancer attributes against human lung carcinoma (A549) cell line via induction of apoptosis mechanism. Initially, the biosynthesis of AgNPs was evident by observing the appearance of dark brown colour solution. UV–Vis spectrum showed characteristic surface plasmon resonance peak at 420 nm. FT-IR spectroscopy demonstrated the presence of distinct functional groups in both the extract and AgNPs. The peaks in XRD pattern corresponded to 101, 111, 200, and 220 crystal planes, thereby representing face-centred cubic silver. The EDX analysis confirmed the reduction of silver ions. The HR-SEM revealed spherical-shaped nanoparticles with an average size of 8–13 nm. In vitro cytotoxicity of extract and AgNPs was determined against A549 cell lines using MTT assay. The AgNPs revealed higher cytotoxity (59.25 ± 1.3–5.55 ± 1.3 %) than the extract (81.48 ± 1.3–16.66 ± 1.6 %) with reduced viabilities of cells at different concentrations. The IC50 values of the extract and AgNPs were calculated as 95.36 and 15.1 µg/mL, respectively. Apoptosis of AgNPs was analyzed using varied techniques as per the standard protocols. Acridine orange staining showed reduced green fluorescence of A549 cells due to the action of AgNPs. DNA fragmentation assay revealed the breakage of DNA double strands of cells and yielded laddered pattern. Flow cytometry analysis depicted increment in the cells count in S phase and concomitant decrement in Go/G1 phase. Quantitative real-time PCR demonstrated the upregulation and downregulation of Bax and Bcl-2 genes, respectively. Additionally, the exposure of A549 cells with AgNPs induced cytochrome C production from depolarized mitochondrial membrane into cytosol, which further upregulated caspase-9 and caspase-3 genes. In conclusion, J. adhatoda leaves-mediated AgNPs induced the apoptosis mechanism in A549 lung adenocarcinoma cells and indicated its paramount role as an effectual anticancer agent in future nanomedicine.

A shift in focus towards precision oncology, driven by revolutionary nanodiagnostics; revealing mysterious pathways in colorectal carcinogenesis.

Multiple molecular mechanisms contribute to the development of colorectal cancer (CRC), with chromosomal instability (CIN) playing a significant role. CRC is influenced by mutations in several important genes, including APC, TP53, KRAS, PIK3CA, BRAF, and SMYD4. The three molecular subtypes of this disease are CIN, MSI-H, and CIMP (CpG-island phenotype). p53 dysfunction and aberrant Wnt signalling are common characteristics of CRC carcinogenesis. Despite advances in conventional therapy, metastatic CRC remains difficult to treat due to toxicity and resistance. Theranostics for cancer could significantly benefit from nanotechnology, as it would enable more targeted, individualised care with fewer side effects. Utilising functionalized nanoparticles has enabled MRI-guided gene therapy, magnetic hyperthermia, chemotherapy, immunotherapy, and photothermal/photodynamic therapy, thereby radically modifying the way cancer is treated. Active targeting using ligands or peptides on nanoparticles improves the delivery of drugs to cancer cells. Nanostructures such as drug peptide conjugates, chitosan nanoparticles, gold nanoparticles, carbon nanotubes, mesoporous silica-based nanoparticles, silver nanoparticles, hybrid lipid-polymer nanoparticles, iron oxide nanoparticles, and quantum dots may enable targeted drug delivery and enhanced therapeutic efficacy against CRC. Nanomedicines are presently being evaluated in clinical trials for the treatment of colorectal cancer, with the promise of more effective and individualised therapies. This article examines current nanomedicine patents for CRC, including the work of Delta-Fly, Merrimack, and Pfenning, Meaning & Partner, among others. In terms of future nanomedicine research and development, ligand production, particle size, and clearance are crucial factors. Lastly, the numerous nanostructures utilized in nanomedicine for targeted drug administration and diagnostics indicate optimistic prospects for enhancing CRC treatment. The successes of nanomedicine research and development for existing colon cancer treatments are also highlighted in this review.

Macrophage fusion event as one prerequisite for inorganic nanoparticle-induced antitumor response.

While most nanomaterials are designed to assist tumor therapy, some inorganic nanoparticles have been reported to impede cancer development. We assume that the immune response elicited by these foreign nanoparticles might be associated with the remodeling of immune landscape in the tumor microenvironment (TME). We studied representative inorganic nanoparticles widely used in the biomedical field and first demonstrated that needle-shaped hydroxyapatite (n-nHA), granule-shaped hydroxyapatite, and silicon dioxide can effectively impair tumor progression in vivo. Substantial multinucleated giant cells (MNGCs) were formed around these antitumor nanoparticles, while the ratio of monocytes and macrophages was decreased in the TME. We found that high expression of the STXBP6 protein induced by n-nHA-treated macrophages triggers autophagy, which markedly promotes macrophage fusion into MNGCs. In this way, extensive depletion of tumor-associated macrophages in the TME was achieved, which suppressed tumor growth and metastasis. This intrinsic antitumor immunity of inorganic nanoparticles should not be neglected when designing future nanomedicines to treat cancer.

Fabrication, optimization, and characterization of pH-responsive PEGylated nanoniosomes containing gingerol for enhanced treatment of breast cancer.

Multiple potential drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated gingerol-loaded niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human breast cancer cells. The preparation procedure was modified by adjusting the drug concentration, lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the gingerol-loaded niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed drug diffusion at physiological pH and significant drug diffusion under acidic conditions (pH = 5.4), making it a promising option for cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3 breast cancer cells, attributed to the presence of gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and VEGF genes, along with up-regulation of the expression of BAX, CASP9, CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible niosomes in the future of nanomedicine, enabling more precise and effective treatment of cancers.

"One-for-All" approach: a black technology for nanomedicine development?

Cancer nanomedicines require different, even opposite, properties to voyage the cascade drug delivery process involving a series of biological barriers. Currently-approved nanomedicines can only alleviate adverse effects but cannot improve patient survival because they fail to meetall the requirements. Therefore, nanocarriers with synchronized functions are highly requisite to capacitate efficient drug delivery and enhanced therapeutic efficacies. This perspective article summarizes recent advances in thetwo main strategies for nanomedicine design, the All-in-One approach (integration of all the functions in one system) and the One-for-All approach (one functional group with proper affinity enables all the functions), and presents our views on future nanomedicine development.

Anisotropic α-Fe2O3/AgAu/Polydopamine Nanostructures for Photothermally Enhanced Antibacterial Applications

Multifunctional photothermal nanomaterials offer notable opportunities for antimicrobial therapy due to their excellent antibacterial activities without leading to drug resistance. Herein, we report a facile one-step strategy for fabricating anisotropic corn-like α-Fe2O3/AgAu/polydopamine (PDA) nanospindles with photothermally enhanced antibacterial performance. The AgAu bimetallic nanocrystals sandwiched between the α-Fe2O3 core and the PDA shell are achieved by simultaneous reduction from AgNO3 and HAuCl4 during the oxidative polymerization of dopamine and galvanic replacement reaction between the obtained Ag nanocrystals and Au precursor. The inner nanostructure and atom ratio of AgAu bimetallic nanocrystals can be modulated by varying the experimental parameter, thus further controlling the photothermal activities. In comparison to α-Fe2O3/Au/PDA, Fe2O3/Ag1.7Au0.8/PDA (50 μg/mL) has a better photothermal conversion effect (60.69%). Moreover, the α-Fe2O3/Ag1.7Au0.8/PDA nanospindle exhibits moderate antibacterial activity, which may be derived from Ag+ release. Under application of near-infrared light irradiation, the corn-like α-Fe2O3/Ag1.7Au0.8/PDA nanospindles (50 μg/mL) exhibit a photothermally enhanced sterilization effect against both Escherichia coli and Staphylococcus aureus (99.99%). This “Ag+ release–photothermal” coupling sterilization method provides a simple synergistic antimicrobial therapy strategy, which possesses great promise for future nanomedicine against bacteria in water treatment.

Engineering of Lurasidone Hydrochloride Loaded Niosomes for Enhancing the Antipsychotic Potential for Nasal Administration

Background: Drugs having high first-pass metabolism or that are susceptible to enzymatic degradation can be administered through the nasal route to avoid their degradation. Lurasidone exhibits less toxicity and side effects as compared to its sister drugs like risperidone, ziprasidone, clozapine, etc. Objectives: The present study aimed to develop Lurasidone loaded niosomes for nasal delivery. Methods: Lurasidone niosomes were developed by adapting the ether injection method and optimized using a central composite design. In vitro and in vivo studies were conducted using optimized formulation. Results: The findings showed that the optimized formulation exhibited a particle size of 159.02 ± 0.58 nm and an entrapment efficiency of 91.6 ± 1.6%. The findings from the nasal histopathological analysis revealed that the optimized formulation was non-irritant and non-toxic for nasal mucosa. The findings from in vitro studies revealed 94.61 ± 0.27% of drug release from optimized formulation F7 throughout 24 hrs. The findings of in vivo (Albino Wistar rats) studies demonstrated that various pharmacokinetic parameters (Cmax, Tmax, AUC(0-24), T1/2, Vd and Cl) and pharmcodynamic parameters (conditioned avoidance response, biochemical estimation using oxidative markers such as superoxide dismutase, malondialdehyde and glutathione) were significantly improved compared to marketed tablets (Lurasid® 40 mg) and pure drug suspension. Optimized formulation F-7 exhibited 4.9 times more bioavailability than that of pure drug suspension following intranasal administration. Conclusion: These findings indicate that nasal niosomal formulation of Lurasidone HCl is a promising nanoplatform for enhancing the overall performance of Lurasidone. These results could open new avenues into the future of nanomedicine.

Lipid nanomaterials-based RNA therapy and cancer treatment.

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

The application of carbon dots in tumor immunotherapy: Researches and prospects

AbstractSince the rapid development of nanomedicine in oncotherapy, multiple nanomaterials are adopted to regulate the immune system in cancer individuals. Tumor immunotherapy enhances the immune function of patients to achieve the purpose of killing tumor cells by utilizing the organism immune mechanism. As emerging inorganic carbon nanoparticles, carbon dots (CDs) have been found as photosensitizers, vaccines, immunoadjuvants, and so on for cancer treatment due to their unique structure and property, such as effective platforms for drug delivery, immunomodulation, and phototherapy. In this review, we mainly discuss the recent application of CDs in tumor immunotherapy and the prospects of CDs in the field of immune medicine. By assessing the achievements and challenges of CDs in tumor immunotherapy, our review would provide mechanistic insights into the evolution of future nanomedicine.

Phase separation‐induced nanoprecipitation for making polymer nanoparticles with high drug loading

AbstractIncreasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug‐loading nanoparticles have demonstrated unique advantages such as less carrier material used, better‐controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation‐induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent‐water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co‐precipitation thus the formation of high drug‐loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt‐induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines.

An acid-activatable nanosensitizer library realizes tunable pyroptosis activation in tumors

Pyroptosis has been viewed as a potential novel pathway toward tumor immunity, yet activating specific pyroptosis in tumor cells remains challenging. Recently in <i>Nature Nanotechnology</i>, Wang, Zhang, You, and colleagues reported a library of acid-activatable nanophotosensitizers that target distinct stages of endosome maturation, attaining tunable pyroptosis. This outstanding work may provide new insights into the creation of future nanomedicine with pyroptosis-modulating capacity for clinical applications.

Organic and inorganic nanomedicine for combination cancer therapies.

In many cases, a single mode of cancer therapy shows limited efficacy in treating complex and heterogeneous tumors. To improve cancer treatment, combining chemo-, photodynamic-, photothermal-, radio-, and immunotherapy is clinically recognized. When different therapeutic treatments are combined, they often show synergetic effects that further improve therapeutic outcomes. In this review, we introduce nanoparticle (NP)-based combination cancer therapies that use organic and inorganic NPs. Liposomes, polymers, and exosomes can be prepared with amphiphilic properties, high physical stability, and low immune response to treat cancers in a multimodal way. Inorganic NPs, including upconversion, plasmonic, and mesoporous silica NPs, have emerged as a new technology for photodynamic-, photothermal-, and immunotherapy. These NPs can simultaneously carry multiple drug molecules and deliver them efficiently to tumor tissue, as demonstrated in many studies. In addition to reviewing recent advances in organic and inorganic NPs used in combination therapy for cancers, we also discuss their rational design and the outlook for future nanomedicine development.

Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment.

Glioblastoma is the most common and lethal brain tumor in adults. The incorporation of temozolomide (TMZ) into the standard treatment has increased the overall survival rate of glioblastoma patients. Since then, significant advances have been made in understanding the benefits and limitations of TMZ. Among the latter, the unspecific toxicity of TMZ, poor solubility, and hydrolyzation are intrinsic characteristics, whereas the presence of the blood-brain barrier and some tumor properties, such as molecular and cellular heterogeneity and therapy resistance, have limited the therapeutic effects of TMZ in treating glioblastoma. Several reports have revealed that different strategies for TMZ encapsulation in nanocarriers overcome those limitations and have shown that they increase TMZ stability, half-life, biodistribution, and efficacy, offering the promise for future nanomedicine therapies in handling glioblastoma. In this review, we analyze the different nanomaterials used for the encapsulation of TMZ to improve its stability, blood half-life and efficacy, paying special attention to polymer- and lipid-based nanosystems. To improve TMZ drug resistance, present in up to 50% of patients, we detail TMZ combined therapeutic with i) other chemotherapies, ii) inhibitors, iii) nucleic acids, iv) photosensitizers and other nanomaterials for photodynamic therapy, photothermal therapy, and magnetic hyperthermia, v) immunotherapy, and vi) other less explored molecules. Moreover, we describe targeting strategies, such as passive targeting, active targeting to BBB endothelial cells, glioma cells, and glioma cancer stem cells, and local delivery, where TMZ has demonstrated an improved outcome. To finish our study, we include possible future research directions that could help decrease the time needed to move from bench to bedside.