This work investigates hybrid ceramic/polymeric sono-responsive nanomaterials made of amorphous titanium dioxide (aTiO2) and a branched poly(ethylene oxide)-poly(propylene oxide) block copolymer surface-modified with the shuttle peptide cyclic Arg-Gly-Asp-d-Phe-Val that targets the αvβ3 integrin overexpressed in the blood-brain barrier endothelium and glioblastoma cells for the actively targeted sonodynamic therapy of brain cancer. The size of the nanoparticles is ∼100 nm, as measured by dynamic light scattering. Nanostructural analysis by high resolution-electron microscopies reveals that the nanoparticles consist of a porous aTiO2 matrix with the polymeric amphiphile homogeneously incorporated in it. High-resolution X-ray photoelectron spectroscopy demonstrates the exposure of the shuttle peptide on the nanoparticle surface. The compatibility, uptake, and sonodynamic efficacy in vitro are studied in 2D and 3D cultures of the glioblastoma cell line U87. Results confirm the good cell compatibility of the nanoparticles and the contribution of the shuttle peptide to significantly increase their uptake and anticancer efficacy in vitro. Moreover, the shuttle peptide modification leads to a 6-fold increase in the nanoparticle accumulation in the brain and a sharp decrease in the accumulation in the liver of healthy mice upon one single intravenous injection, highlighting the promise of this platform for the targeted SDT of brain tumors.

Gadolinium Based Contrast Agents (GBCAs) are routinely used in the clinical practice to enhance the diagnostic potential of MRI. Their contrast enhancing capabilities rely on their ability to increase the relaxation rate of tissue water protons. This property is expressed by the relaxivity, whose value is determined by structural, electronic and dynamic characteristics of the GBCA. Based on extensive experimental work over the past four decades and the well-established theory of paramagnetic relaxation, it is usually possible to correlate observed relaxivity values to specific molecular properties. Key determinants include the number of water molecules and/or exchangeable protons in the first and second coordination spheres, their distance from the paramagnetic Gd3+ ion, the ion's electronic relaxation time, molecular reorientation time, and the exchange rate of the coordinated water molecules. Understanding the key factors that affect relaxivity has enabled the design of systems with optimized structural and dynamic properties. However, some examples demonstrate exceptional relaxivity which cannot be fully explained by the established theory. In particular, GBCAs within confined environments show significant promise for developing high-relaxivity agents. Overall, one may state that nowadays it is possible to attain highly efficient GBCAs thanks to the in-depth understanding of the structural and dynamic determinants of their relaxivity, together with the optimization of their in vivo stability and biodistribution/excretion properties. This knowledge is crucial for the rational design of the next generation of MRI CAs. The domain of Molecular Imaging will also largely benefit from these efforts.

Theranostic nanoparticles like polymer conjugated gold nanoparticles are at the cutting edge of cancer therapy, offering an integrated platform for simultaneous diagnosis and treatment. In this study, we report a nanoconjugate (P2AuNPs) by combining doxorubicin (DOX) tethered polymeric prodrug based bicontinuous nanoparticles (P2NPs), developed recently by us, with gold nanoparticles (AuNPs). The AuNPs were generated by in situ reduction of HAuCl4, where different polymer functionalities served the role of reducing and stabilizing agents. The bicontinuous morphology of P2NPs provided a unique template for the growth of gold nanoparticles, resulting in an overall raspberry-like morphology. Compared to existing small-sized theranostic AuNPs, which often trigger systematic cytotoxicity, the synthesized P2AuNPs had an ideal size of ∼90 nm for passive targeting of cancer cells through leaky tumor blood vessels. Furthermore, the embedded gold nanoparticles in P2AuNPs nanoconjugate served as a nanometal surface energy transfer (NSET) pair with the covalently attached DOX molecules, resulting in the significant quenching of DOX (turned 'OFF' state) fluorescence at physiological pH (7.4) as confirmed through steady-state and time-resolved fluorescence measurements. It was also possible to recover the quenched DOX fluorescence (turned 'ON' state) with the release of DOX selectively in cancer cell lines, plausibly due to higher glutathione (GSH) levels and acidic pH. In vitro cellular studies asserted the safe nature of P2NPs against non-cancerous cells (HEK-293T) while exhibiting significantly higher drug-induced cytotoxicity against cancerous cells (MCF-7) compared to free DOX. Moreover, when P2AuNPs were incubated with HEK-293T and MCF-7 cells, a fluorescence turn 'ON' for DOX was observed only in MCF-7 cells after the release of DOX, thereby providing an opportunity to improve the sensitivity of imaging and real-time monitoring of drug release. Together, this integrated theranostic system not only has the potential to enhance the precision and effectiveness of cancer therapy but also offers improved monitoring capabilities, representing a significant advancement in tailored nanomedicine.

Kidney diseases, posing significant global public health challenges due to their complex pathogenesis and diagnostic/therapeutic difficulties, have seen emerging advancements through nanomedicine. In diagnostics, nanoparticles leverage unique physicochemical properties to enhance imaging precision. Superparamagnetic iron oxide nanoparticles improve magnetic resonance imaging sensitivity by amplifying T2-weighted contrast, while microbubbles/nanobubbles enhance ultrasound resolution via signal reflection. Quantum dots and gold nanoparticles optimize photoacoustic imaging with superior fluorescence and photostability. Therapeutically, nanoparticle-based drug delivery systems demonstrate targeted delivery, reduced systemic toxicity, and improved drug stability and bioavailability in preclinical studies. Nanocarrier-integrated stem cell and gene therapies further show potential in repairing renal cells and mitigating kidney injury. This review systematically examines nanomedicine's dual diagnostic and therapeutic roles in kidney diseases, compares strengths and limitations of various nanodelivery platforms, and addresses current challenges in clinical translation. By exploring novel nanotechnology-driven strategies, it aims to guide future research toward effective, tailored therapies for improved renal disease management.

In this report, we present a novel one-pot synthesis of Cu-In-S/ZnS quantum dots (QDs) in buffer solution as a facile route to biocompatible nanoscale imaging probes, with emission wavelengths as far as 675 nm in the biologically important near-infrared spectral region and quantum yields of up to 16%. Whilst a simple route, our method produced particles that displayed exceptionally high cell viability with facile applications in in vivo imaging, highlighting the potential of these QDs as advanced imaging probes.

RNA therapeutics represent a pivotal advancement in contemporary medicine, pioneering innovative treatments in oncology and vaccine production. The inherent instability of RNA and its delivery challenges necessitate the use of lipid-based nanoparticles as crucial transport vehicles. This research focuses on the design, simulation, and optimization of various microfluidic channel configurations for fabricating poly(dimethylsiloxane) (PDMS) microfluidic chips, aimed at producing lipid nanoparticles (LNPs) encapsulating green fluorescent protein mRNA (GFP mRNA). Aiming for high mixing efficiency and acceptable pressure drop suitable for scale-up, we designed and improved multiple microfluidic channels featuring flow focusing and diverse tilted rectangular baffle structures via computational fluid dynamics (CFD). Simulation results indicated that baffle angles ranging from 70 to 90° exhibited similar mixing efficiencies at different total flow rates, with pressure drops increasing alongside the baffle angle. Additionally, increasing the baffle length at a fixed angle of 70° not only improved mixing efficiency but also increased the pressure drop. To validate these findings, PDMS microfluidic chips were fabricated for all designs to prepare empty LNPs. The baffle structure with a 70° angle and 150 μm length was identified as the best configuration based on both simulation and experimental results. This optimal design was then used to prepare LNPs with varying GFP mRNA concentrations, demonstrating that an N/P ratio of 5.6 yielded the highest transfection efficiency from in vitro experiments. This work not only advances the production of lipid-based nanoparticles through microfluidics but also provides a scalable and reproducible method that can potentially enhance the clinical translation of RNA therapeutics.

Nanoparticles (NPs) represent a unique class of structures in the modern world. In comparison to macro- and microparticles, NPs exhibit advantages due to their physicochemical properties. This has resulted in their extensive application not only in technical and engineering sciences, but also in pharmacy and medicine. A recent analysis of the scientific literature revealed that the number of articles related to the search term "nanoparticle drugs" has exceeded 65,000 in the last decade alone, according to PubMed. The growth of scientific publications on NPs and nanomaterials (NMs) in pharmacy demonstrates the rapidly developing interest of scientists in exploring alternative ways to deliver drugs, thereby improving their pharmacokinetic and pharmacodynamic properties, and the increased biocompatibility of many nanopharmaceuticals is a unique key to two mandatory pharmaceutical requirements-drug efficacy and safety. A comprehensive review of the literature indicates that the modern pharmaceutical industry is increasingly employing nanostructures. The exploration of their physicochemical properties with a subsequent modern approach to quality control remains the main task of modern pharmaceutical chemistry. The primary objective of this review is to provide a comprehensive overview of data on NPs, their physicochemical properties, and modern approaches to their synthesis, modification of their surface, and application in pharmacy.

Heterotopic Ossification (HO), refers to pathological extra skeletal bone formation, and there are currently no reliable methods except surgery to reverse these unexpected calcified tissues. Apoptotic vesicles (ApoEVs) are membrane-bound vesicles released by apoptotic cells, which are involved in metabolism regulation and intercellular communication. Due to its superior trauma-healing ability, the hard palate mucosa is expected to become an essential resource for tissue engineering. This work presents a minimally invasive nanotherapy based on an engineered apoEV. Briefly, apoEVs were extracted from hard palate mucosa and engineered with bone-targeting peptide SDSSD to treat HO. This engineered apoEV not only can achieve directed localization of heterotopic bones but also has the compelling dual function of promoting osteoclastic differentiation while inhibiting osteogenic differentiation. The underlying mechanism involves the activation of Hippo and Notch pathways, as well as the regulation of pyrimidine metabolism. We envision that this engineered apoEV may be a feasible and effective strategy for reversing HO.

In this study, a smart hybrid liposome system was achieved combining a self-assembling biopolymer conjugate (human serum albumin-hyaluronic acid) with targeting and redox-responsive activity with dioleoyl phosphatidylethanolamine, a fusogenic phospholipid. The obtained hybrid liposomal structures were found to possess suitable physicochemical properties for cancer therapy application, with mean size of 65 nm, negative surface charge (-27 mV) and the ability to efficiently encapsulate Doxorubicin in the inner liposomal core with high efficiency. The drug loaded hybrid liposomes (DOX@HBLs) were able to trigger the drug release under simulated acidic and redox conditions of the tumor environment, whereas the biological characterization demonstrated the safety and the selectivity of the formulation, able to target the cancer cells (toxicity similar to that of the free drug) while sparing the healthy cells (viability > 90 % in all cases). Furthermore, compared to free drug, DOX@HBLs were able to reduce cell motility, impair metabolic pathways essential for cancer progression, and effectively inhibit spheroid formation (by almost 50 % after 20 days incubation) in both Estrogen Receptor-positive and Triple Negative Breast Cancer cells, demonstrating their high potential as unconventional drug delivery vectors in cancer therapy.

The use of natural killer (NK) cell-based immunotherapy has been extensively explored in clinical trials for multiple types of tumors and has surfaced as a promising approach in tumor immunotherapy. Interleukins (ILs), a vital class of cytokines, play a crucial role in regulating several functions of NK cells, thereby becoming a focal point in the advancement of NK cell-based therapies. Nonetheless, the use of ILs as single agents is significantly constrained by their short half-life, limited efficacy, and adverse reactions. Currently, nanomaterials are being progressively employed in the delivery of ILs to enhance NK cell-based immunotherapy. However, there is currently a lack of comprehensive reviews summarizing the design of NK-cell-targeted nanomaterials and related systems for delivery of ILs. Furthermore, certain nanomaterials, either alone or in conjunction with other therapeutics, can also promote the secretion of ILs, representing a promising avenue for further exploration. Accordingly, this review begins by outlining various types of ILs and subsequently discusses the advancements in applying nanomaterials for IL delivery. It also examines the potential of nanomaterials to enhance IL secretion from other immune cells, thereby influencing the NK cell functionality. Lastly, this review addresses the challenges associated with using nanomaterials in these contexts and offers perspectives for future research. This study aims to provide valuable insights into the development of NK cell immunotherapy and innovative nanomaterial-based drug delivery systems.

Medical interventions often require timed series of doses, thus necessitating accurate medical record-keeping. In many global settings, these records are unreliable or unavailable at the point of care, leading to less effective treatments or disease prevention. Here we present an invisible-to-the-naked-eye on-patient medical record-keeping technology that accurately stores medical information in the patient skin as part of microneedles that are used for intradermal therapeutics. We optimize the microneedle design for both a reliable delivery of messenger RNA (mRNA) therapeutics and the near-infrared fluorescent microparticles that encode the on-patient medical record-keeping. Deep learning-based image processing enables encoding and decoding of the information with excellent temporal and spatial robustness. Long-term studies in a swine model demonstrate the safety, efficacy and reliability of this approach for the co-delivery of on-patient medical record-keeping and the mRNA vaccine encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This technology could help healthcare workers make informed decisions in circumstances where reliable record-keeping is unavailable, thus contributing to global healthcare equity.

Breast cancer is one of the most common types of cancer, however, preventive screening has contributed to a significant reduction in mortality over the past four decades. The first-line screening methods for breast cancer, such as mammography and tomosynthesis, are x-ray-based modalities. Unfortunately, their cancer detection rates are low in patients with dense breasts. These, and other high-risk women, are now encouraged to receive supplemental screening. The supplemental imaging methods are diverse, including ultrasound, MRI, nuclear imaging, and X-ray-based modalities such as breast CT and contrast-enhanced mammography/tomosynthesis. Due to their low cost and wide availability, x-ray-based modalities see significant clinical use worldwide. These techniques benefit from the use of contrast agents, which are currently iodinated small molecules designed for other purposes. Consequently, developing new contrast agents that are specifically for breast cancer screening is of interest. This review describes these modalities and the nanoparticle-based contrast agents being researched for their enhanced performance. The relevant parameters for nanoparticle-based contrast agent design are evaluated, including contrast generation and potential biointeractions. Iodinated agents are discussed for comparison. Nanoparticles covered include silver sulfide, silver telluride, gold, and bismuth sulfide-based agents, among others. Finally, perspectives on future developments in this field are offered.

Microrobotic swarms hold great promise for the revolution of cancer treatment. The coordination of miniaturized microrobots offers a unique approach to treating cancers at the cellular level with enhanced delivery efficiency and environmental adaptability. Prior studies have summarized the design, functionalization, and biomedical applications of microrobotic swarms. The strategies for actuation and motion control of swarms have also been introduced. In this review, we first give a detailed introduction to microrobot swarming. We then explore the design of microrobots and microrobotic swarms specifically engineered for cancer therapy, with a focus on tumor targeting, infiltration, and therapeutic efficacy. Moreover, the latest developments in active delivery methods and imaging techniques that enhance the precision of these systems are discussed. Finally, we categorize and analyze the various cancer therapies facilitated by functional microrobotic swarms, highlighting their potential to revolutionize treatment strategies for different cancer types.

Renal Cell Carcinoma (RCC) poses challenges for conventional treatment methods, but recent advancements indicate the potential of nanoparticles (NPs) in enhancing chemotherapy efficacy. This study focuses on developing non-toxic NPs from sucrose and l-serine via hydrothermal synthesis to produce Sucrose Carbon Dots (Suc CDs), designed for renal clearance to deliver hydrophilic drugs for the treatment of RCC. Suc CDs with a size of 4 nm exhibit high fluorescence with a fluorescence quantum yield of 58% and high drug loading capacity without toxicity to normal cell lines (renal tubular cells). Under in vitro conditions, Suc CDs alone are non-toxic, while Suc CDs with DOX display improved anticancer effects on Renca cells (cancer cell line). Under in vivo conditions, Suc CDs loaded with DOX outperform DOX alone with reduced toxicity to normal cells. Biodistribution study of Suc CDs revealed prolonged tumour site accumulation. This research demonstrates that renal clearable Suc CDs loaded with DOX exhibit superior anti-cancer activity, and are free of side effects, suggesting promising therapeutic potential for human RCC.

Supraparticles (SPs) with unique properties are emerging as versatile platforms for applications in catalysis, photonics, and medicine. However, the synthesis of novel SPs with complex internal structures remains a challenge. Self-Assembled Multilayered Supraparticles (SAMS) presented here are composed of concentric lamellar spherical structures made from metallic nanoparticles, formed from a synergistic three-way interaction phenomenon between gold nanoparticles, lipidoid, and gelatin, exhibiting interlayer spacing of 3.5  ± 0.2 nm within a self-limited 156.8  ± 56.6 nm diameter. The formation is critically influenced by both physical (including nanoparticle size, lipidoid chain length) and chemical factors (including elemental composition, nanoparticle cap, and organic material), which collectively modulate the surface chemistry and hydrophobicity, affecting interparticle interactions. SAMS can efficiently deliver labile payloads such as siRNA, achieving dose-dependent silencing in vivo, while also showing potential for complex payloads such as mRNA. This work not only advances the field of SP design by introducing a new structure and interaction phenomenon but also demonstrates its potential in nanomedicine.

Nanoparticles (NPs) have been extensively researched for targeted diagnostic imaging and drug delivery, yet their clinical translation remains limited, with only a few achieving Food and Drug Administration approval. This limited success is primarily due to challenges in achieving precise organ- or tissue-specific targeting, which arise from off-target tissue accumulation and suboptimal clearance profiles. Herein we examine the critical role of physicochemical properties, including size, surface charge, shape, elasticity, hardness, and density, in governing the biodistribution, targetability, and clearance of NPs. We highlight recent advancements in engineering NPs for targeted imaging and drug delivery, showcasing both significant progress and the remaining challenges in the field of nanomedicine. Additionally, we discuss emerging tools and technologies that are being developed to address these challenges. Based on recent insights from materials science, biomedical engineering, computational biology, and clinical research, we propose key design considerations for next-generation nanomedicines with enhanced organ selectivity.

Iron-oxide nanoparticles (IONPs) have garnered substantial attention in both research and technological domains due to their exceptional chemical and physical properties. These nanoparticles have mitigated the adverse effects of conventional treatment procedures by facilitating advanced theranostic approaches in integration with biomedicine. These IONPs have been extensively utilized in MRI (as contrast agents in diagnosis), drug delivery (as drug carriers), and hyperthermia (treatment), demonstrating promising results with potential for further enhancement. This study elucidates the operational principles of these NPs during diagnosis, drug delivery, and treatment, and emphasizes their precision and efficacy in transporting therapeutic agents to targeted sites without drug loss. It also analyses various challenges associated with the application of these IONPs in this field, such as biocompatibility, agglomeration, and toxicity. Furthermore, diverse strategies have been delineated to address these challenges. Overall, this review provides a comprehensive overview of the applications of IONPs in the field of biomedicine and treatment, along with the associated challenges. It offers significant assistance to researchers, professionals, and clinicians in the field of biomedicine.

Boron agent is widely accepted as one of the most important factors in boron neutron capture therapy (BNCT). In this study, boron carbide (B4C) nanoparticles were subjected to chemical modification, with the folic acid moiety linked to the surface of the particles by varying the segments of the covalent linker polyethylene glycol (PEG) through γ-aminopropyltriethoxysilane (APTES) functionalization. The resultant products were three boron agents, termed as B4C-APTES-FA, B4C-APTES-PEG2K-FA, and B4C-APTES-PEG5K-FA. A comparison was made between these products and the pristine B4C nanoparticles by investigating their physicochemical properties and biological performances, including hemolysis, cytotoxicity, and cellular uptake. Subsequently, the modified B4C-APTES-PEG2K-FA nanoparticles were subjected to in vivo safety assays and biodistribution investigations in mice at various dosages. Upon characterization using ICP-OES, it was found that the boron contents were the highest in the lungs, followed by the liver, spleen, kidneys, hearts, and tumors, and the lowest in the brain and muscles. The boron content in the tumor reached as high as 50 μg per g of dried tissue weight after 24 h of intravenous injection (I.V.), while the tumor-to-muscle and tumor-to-brain ratios of boron contents were found to exceed 3 following 24 hours of intravenous injection. These findings suggest that B4C nanoparticles are promising for BNCT owing to their high boron content, satisfactory biocompatibility, and abundant chemical modification sites.

Delivery of nanoparticles (NPs) to solid tumors has long relied on enhanced permeability and retention (EPR) effect, involving permeation of NPs through a leaky vasculature with prolonged retention by reduced lymphatic drainage in tumor. Recent research studies and clinical data challenge EPR concept, revealing alternative pathways and approaches of NP delivery. The area was significantly impacted by the implementation of intravital optical microscopy, unraveling delivery mechanisms at cellular level in vivo. This review presents analysis of the reasons for EPR heterogeneity in tumors and describes non-EPR based concepts for drug delivery, which can supplement the current paradigm. One of the approaches is targeting tumor endothelium by NPs with subsequent intravascular drug release and gradient-driven drug transport to tumor interstitium. Others exploit various immune cells for tumor infiltration and breaking endothelial barriers. Finally, we discuss the involvement of active transcytosis through endothelial cells in NP delivery. This review aims to inspire further understanding of the process of NP extravasation in tumors and provide insights for developing next-generation nanomedicines with improved delivery.

Cuproptosis has gained significant attention among different cell death pathways in cancer therapy, which relies on the excessive accumulation of Cu2+ in mitochondria of tumor cells. Nevertheless, the high levels of glutathione in tumor microenvironment chelates with Cu2+ and thereby reducing its cytotoxicity. In this study, we designed core-shell porous organic polymers (POPs) nanoparticles to deliver and accumulate Cu2+ in tumor cells for enhanced cuproptosis. The porous organic polymers, containing bipyridine structural units, were synthesized on the aminated silica template, followed by the coordination of Cu2+ and the loading of artesunate (ART) as the sonosensitizer, yielding the Cu/ART@Hpy nanoparticles. In the acidic tumor microenvironment, the nanoparticles realized pH-responsive release of Cu2+. Meanwhile, the generation of ROS under ultrasound irradiation depleted intracellular glutathione, leading to the increased intracellular accumulation of Cu2+ for cuproptosis and triggering multiple cell death mechanisms for sonodynamically enhanced tumor therapy. Our study highlights the potential of the porous organic polymer as a platform for cuproptosis and synergistic tumor therapy. STATEMENT OF SIGNIFICANCE: Cuproptosis is induced by the excessive accumulation of Cu²⁺ within the mitochondria of tumor cells. However, the high level of glutathione in the tumor microenvironment can chelate Cu²⁺, thereby reducing the therapeutic efficacy. In this study, we developed the core-shell structured Cu/ART@Hpy nanoparticles for pH-responsive delivery of Cu²⁺. Under ultrasound irradiation, the generated reactive oxygen species deplete intracellular glutathione, enhancing Cu²⁺ accumulation for cuproptosis and activating multiple cell death pathways. The Cu/ART@Hpy nanoparticles enable sonodynamically enhanced cuproptosis, achieving synergistic tumor therapy.

Current research in nanotechnology is improving or developing novel applications that could improve disease diagnosis or treatment. This study highlights several nanoscale drug delivery technologies, such as nano micelles, nanocapsules, nanoparticles, liposomes, branching dendrimers, and nanostructured lipid formulations for the targeted therapy of ovarian cancer (OC), to overcome the limitations of traditional delivery. Because traditional drug delivery to malignant cells has intrinsic flaws, new nanotechnological-based treatments have been developed to address these conditions. Ovarian cancer is the most common gynecological cancer and has a higher death rate because of its late diagnosis and recurrence. This review emphasizes the discipline of medical nanotechnology, which has made great strides in recent years to solve current issues and enhance the detection and treatment of many diseases, including cancer. This system has the potential to provide real-time monitoring and diagnostics for ovarian cancer treatment, as well as simultaneous delivery of therapeutic agents.

Bioimaging is very important in medicine, especially in cancer diagnosis and treatment. In this study, we determined the impact of different components on the optical and magnetic properties of various conjugates. The three components, i.e., Fe3O4 nanoparticles (NPs), drug (doxorubicin - Dox), and dye (Cyanine 5.5 - Cy 5.5), were incorporated to form the four conjugates of A1 (Fe3O4-Cy 5.5), A2 (Fe3O4-Dox), A3 (Fe3O4-Cy 5.5-Dox), and A4 (Cy 5.5-Dox). The conjugates were characterized by DLS, UV-Vis spectra, fluorescence spectra, VSM, XRD, and TEM methods. After that, in vitro near-infrared (NIR) fluorescence imaging and magnetic resonance imaging (MRI) experiments were carried out to determine the conjugate suitable for bimodal imaging. The results show that A3 exhibits the highest quantum yield and radiance ratio and also has the highest ratio of r 2/r 1. The in vivo MRI and NIR fluorescent imaging results of CT26-bearing mice injected with A3 conjugates prove that the conjugate has potential in bimodal cancer imaging applications.

Non-coding RNAs (ncRNAs) have a significant role in gene regulation, especially in cancer and inflammatory diseases. ncRNAs, such as microRNA, long non-coding RNAs, and circular RNAs, alter the transcriptional, post-transcriptional, and epigenetic gene expression levels. These molecules act as biomarkers and possible therapeutic targets because aberrant ncRNA expression has been directly connected to tumor progression, metastasis, and response to therapy in cancer research. ncRNAs' interactions with multiple cellular pathways, including MAPK, Wnt, and PI3K/AKT/mTOR, impact cellular processes like proliferation, apoptosis, and immune responses. The potential of RNA-based therapeutics, such as anti-microRNA and microRNA mimics, to restore normal gene expression is being actively studied. Additionally, the tissue-specific expression patterns of ncRNAs offer unique opportunities for targeted therapy. Specificity, stability, and immune responses are obstacles to the therapeutic use of ncRNAs; however, novel strategies, such as modified oligonucleotides and targeted delivery systems, are being developed. ncRNA profiling may result in more individualized and successful treatments as precision medicine advances, improving patient outcomes and creating early diagnosis and monitoring opportunities. The current review aims to investigate the roles of ncRNAs as potential biomarkers and therapeutic targets in cancer and inflammatory diseases, focusing on their mechanisms in gene regulation and their implications for non-invasive diagnostics and targeted therapies. A comprehensive literature review was conducted using PubMed and Google Scholar, focusing on research published between 2014 and 2025. Studies were selected based on rigorous inclusion criteria, including peer-reviewed status and relevance to ncRNA roles in cancer and inflammatory diseases. Non-English, non-peer-reviewed, and inconclusive studies were excluded. This approach ensures that the findings presented are based on high-quality and relevant sources.

Metal-phenolic networks (MPNs), which comprise supramolecular amorphous networks formed by interlinking polyphenols with metal ions, garner escalating interest within the realm of nanomedicine. Presently, a comprehensive synthesis of the cumulative research advancements and utilizations of MPNs in nanomedicine remains absent. Thus, this review endeavors to firstly delineate the characteristic polyphenols, metal ions, and their intricate interaction modalities within MPNs. Subsequently, it elucidates the merits and demerits of diverse synthesis methodologies employed for MPNs, alongside exploring their potential functional attributes. Furthermore, it consolidates the diverse applications of MPNs across various nanomedical domains encompassing tumor therapy, antimicrobial interventions, medical imaging, among others. Moreover, a meticulous exposition of the journey of MPNs from their ingress into the human body to eventual excretion is provided. Lastly, the persistent challenges and promising avenues pertaining to MPNs are delineated. Hence, this review offering a comprehensive exposition on the current advancements of MPNs in nanomedicine, consequently offering indirect insights into their potential clinical implementation.

The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy.

SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC50 = 0.24 ± 0.01 µM) with IC50 value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC90 = 6.07 ± 0.41 µM) as compared with SN-38 (IC90 = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC90 >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect.

This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers.

Nanozymes, nanomaterials with intrinsic enzyme activity, have garnered significant attention in recent years due to their catalytic abilities comparable to natural enzymes, cost-effectiveness, high catalytic activities, and stability against environmental fluctuations. As functional analogs of natural enzymes, nanozymes participate in various critical metabolic processes, including glucose metabolism, lactate metabolism, and the maintenance of redox homeostasis, all of which are essential for normal cellular functions. However, disruptions in these metabolic pathways frequently promote tumorigenesis and progression, making them potential therapeutic targets. While several therapies targeting tumor metabolism are currently in clinical or preclinical stages, their efficacy requires further enhancement. Consequently, nanozymes that target tumor metabolism are regarded as a promising therapeutic strategy. Despite extensive studies investigating the application of nanozymes in tumor metabolism, relevant reviews are relatively scarce. This article first introduces the physicochemical properties and biological behaviors of nanozymes. Subsequently, we analyze the role of nanozymes in tumor metabolism and explore their potential applications in tumor therapy. In conclusion, this review aims to foster innovative research in related fields and advance the development of nanozyme-based strategies for cancer diagnostics and therapeutics.

Upconversion luminescent materials (UCLMs) have garnered significant attention due to their broad potential applications in fields such as display technology, biological imaging, and optical sensing. However, optimizing crystal phase and morphology remains a challenge. This study systematically investigates the effects of phase transformation and morphology control on the upconversion luminescent properties of K3GaF6:Er3+. By comparing different synthesis methods, we found that the hydrothermal method effectively facilitated the transformation of the NaxK3-xGaF6 crystal phase from cubic to monoclinic, with Na+/K+ ions playing a key role in the preparation process. Furthermore, the hydrothermal method significantly optimized the particle morphology, resulting in the formation of uniform octahedral structures. The 657 nm red emission intensity of the monoclinic phase sample doped with Er3+ was enhanced by 30 times compared to that of the cubic phase, clearly demonstrating the crucial role of phase transformation in luminescent performance. This study emphasizes the synergistic optimization of crystal phase and morphology through phase engineering, which substantially improves the upconversion luminescence efficiency of K3GaF6:Er3+, paving the way for further advancements in the design of efficient upconversion materials.

In the dynamic realm of translational nanorobotics, the endeavor to develop nanorobots carrying therapeutics in rational in vivo applications necessitates a profound understanding of the biological landscape of the human body and its complexity. Within this landscape, biological membranes stand as critical barriers to the successful delivery of therapeutic cargo to the target site. Their crossing is not only a challenge for nanorobotics but also a pivotal criterion for the clinical success of therapeutic-carrying nanorobots. Nevertheless, despite their urgency, strategies for membrane crossing in translational nanorobotics remain relatively underrepresented in the scientific literature, signaling an opportunity for further research and innovation. This review focuses on nanorobots with various propulsion mechanisms from chemical and physical to hybrid mechanisms, and it identifies and describes four essential biological membranes that represent the barriers needed to be crossed in the therapeutic journey of nanorobots in in vivo applications. First is the entry point into the blood stream, which is the skin or mucosa or intravenous injection; next is the exit from the bloodstream across the endothelium to the target site; further is the entry to the cell through the plasma membrane and, finally, the escape from the lysosome, which otherwise destroys the cargo. The review also discusses design challenges inherent in translating nanorobot technologies to real-world applications and provides a critical overview of documented membrane crossings. The aim is to underscore the need for further interdisciplinary collaborations between chemists, materials scientists and chemical biologists in this vital domain of translational nanorobotics that has the potential to revolutionize the field of precision medicine.

Synergistic photodynamic/photothermal therapy (PDT/PTT) can be used to target cancer cells by locally generating singlet oxygen species or increasing temperature under laser irradiation. This approach offers higher tumor ablation efficiency, lower therapeutic dose requirements, and reduced side effects compared to single treatment approaches. However, the therapeutic efficiency of PDT/PTT is still limited by the low oxygen levels within the solid tumors caused by abnormal vasculature and altered cancer cell metabolism. To address these challenges, we developed multifunctional nanoparticles with high catalytic activity for converting tumor hydrogen peroxide (H2O2) into oxygen (O2). Using poly(styrene-co-maleic anhydride) (PSMA) as a cross-linker, we generated compact, highly fluorescent Pdots, used poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) as a near-infrared photosensitizer for both photodynamic and photothermal applications, and incorporated manganese (Mn) ions to catalyze the H2O2-to-O2 conversion. These Mn-doped Pdots significantly enhance O2 production, achieving an enhanced 1O2 quantum yield from 0.46 to 0.64 with the addition of H2O2, achieving the goal of improving PDT efficiency. With this rational design, we produced Pdots with enhanced H2O2-to-1O2 converting ability for potential use in PDT. For photothermal applications, our Pdots generate a photothermal conversion efficiency of 53%. In vitro studies using human MCF7 adenocarcinoma cells confirmed the biocompatibility of these Pdots in the absence of laser exposure with a pronounced cell killing effect under laser irradiation for synergistic PDT/PTT. These results highlight the promise of Pdots in overcoming oxygen limitations, balancing the performance of PDT/PTT, and enhancing the therapeutic efficacy of PDT/PTT in cancer cells in vitro.

Deuterium (2H) MRI is an emerging tool for noninvasive imaging. We explore the integration of 2H MRI with deuterated multifunctional nanopolymers for deuterated particle imaging (DPI). To this end, amine-terminated G5-polyamidoamine (PAMAM) dendrimers were labeled with deuterated acetyl surface groups, leading to highly 2H-loaded bioparticles, making them ideal for imaging studies. The accumulation of ∼5 nm PAMAM dendrimers in the kidneys could then be seen by 2H MRI with high submillimeter resolution. The natural abundance HDO signal provided an internal concentration reference to these measurements, leading to quantitative dynamic maps showing distinct nanopolymer uptakes within the renal compartments. Further, these nanopolymers allowed us to obtain in vivo maps of activity in the lymph nodes in an inflammatory rodent leg model, demonstrating these deuterated nanopolymers' potential as a novel class of contrast agents for the quantitative mapping of physiological processes.

Nanocarriers have shown significant promise in the diagnosis and treatment of various diseases, utilizing a wide range of biocompatible materials such as metals, inorganic substances, and organic components. Despite diverse design strategies, key physicochemical properties, including hydrodynamic diameter, shape, surface charge, and hydrophilicity/lipophilicity, are crucial for optimizing biodistribution, pharmacokinetics, and therapeutic efficacy. However, these properties are often influenced by drug payload, presenting an ongoing challenge in developing versatile platform technologies for theranostics. To enable tissue- and organ-specific targeting while minimizing nonspecific uptake, renal clearable Harvard dots (H-dots) have emerged as a promising organic nanocarrier platform. Composed of an ε-polylysine backbone for a tunable charge, near-infrared fluorophores for tracking their fate in living organisms, and β-cyclodextrins for potential drug delivery, H-dots offer a multifunctional approach to theranostic nanomedicine. Recent studies demonstrate that H-dots are effective for targeted imaging and drug delivery to solid tumors. This review highlights current nanocarrier design strategies and recent advances in H-dot applications for cancer diagnosis and therapy.

Drug delivery to cancer cells continues to present a major therapeutic challenge. Mesenchymal stem cells (MSCs) possess an intrinsic ability to migrate specifically to tumor tissues, making them promising candidates for targeted drug delivery. Evidence from preclinical studies indicates that MSCs loaded with therapeutic anti-cancer agents exhibit considerable anti-tumor activity. Moreover, several clinical trials are currently evaluating their effectiveness in cancer patients. The integration of MSCs with synthetic nanoparticles (NPs) enhances their therapeutic potential, particularly through the use of cell membrane-coated NPs, which represent a significant advancement in the field. This review systematically investigates the tumor microenvironment, the sources of MSCs, the tumor homing mechanisms, and the methods of loading and releasing anticancer drugs from MSCs. Furthermore, cutting-edge strategies to improve the efficacy of MSCs based drug delivery systems (DDS) including the innovative use of MSC membrane coated nanoparticles have been discussed. The study concludes with an overview of the therapeutic use of MSCs as drug carriers, including a detailed analysis of the mechanisms by which MSCs deliver therapeutics to cancer cells, enabling targeted drug delivery. It aims to elucidate the current state of this approach, identify key areas for development, and outline potential future directions for advancing MSCs based cancer therapies.

Trimetallic nanoparticles (TMNPs) have emerged as a pivotal area of research due to their unique properties and diverse applications across medicine, agriculture, and environmental sciences. This review provides several novel contributions that distinguish it from existing literature on trimetallic nanoparticles (TMNPs). Firstly, it offers a focused exploration of TMNPs, specifically addressing their unique properties and applications, which have been less examined compared to other multimetallic nanoparticles. This targeted analysis fills a significant gap in current research. Secondly, the review emphasizes innovative biosynthesis methods utilizing microorganisms and plant extracts, positioning these green synthesis approaches as environmentally friendly alternatives to traditional chemical methods. This focus aligns with the increasing demand for sustainable practices in nanotechnology. Furthermore, the review integrates discussions on both medical and agricultural applications of TMNPs, highlighting their multifunctional potential across diverse fields. This comprehensive perspective enhances our understanding of how TMNPs can address various challenges. Additionally, the review explores the synergistic effects among the different metals in TMNPs, providing insights into how these interactions can be harnessed to optimize their properties for specific applications. Such discussions are often overlooked in existing studies. Moreover, this review identifies critical research gaps and challenges within the field, outlining future directions that encourage further investigation and innovation in TMNP development. By doing so, it proactively contributes to advancing the field. Finally, the review advocates for interdisciplinary collaboration among material scientists, biologists, and environmental scientists, emphasizing the importance of diverse expertise in enhancing the research and application of TMNPs.

Ischemic stroke is the cause of high mortality and disability Worldwide. The material costs of stroke treatment and recovery are constantly increasing, making the search for effective and more cost-effective treatment approaches an urgent task for modern biomedicine. In this study, iron nanoparticles doped with selenium nanoparticles, FeNP@SeNPs, which are three-layered structures, were created and characterized using physical methods. Fluorescence microscopy, inhibitor and PCR analyzes were used to determine the signaling pathways involved in the activation of the Ca2+ signaling system of cortical astrocytes and the protection of cells from ischemia-like conditions (oxygen-glucose deprivation and reoxygenation). In particular, when using magnetic selenium nanoparticles together with electromagnetic stimulation, an additional pathway for nanoparticle penetration into the cell is activated through the activation of TRPV4 channels and the mechanism of their endocytosis is facilitated. It has been shown that the use of magnetic selenium nanoparticles together with magnetic stimulation represents an advantage over the use of classical selenium nanoparticles, as the effective concentration of nanoparticles can be reduced many times over.

Due to the escalating threat of the pathogens' capability of quick adaptation to antibiotics, finding new alternatives is crucial. Although antimicrobial peptides (AMPs) are highly potent and effective, their therapeutic use is limited' as they are prone to enzymatic degradation, are cytotoxic and have low retention. To overcome these challenges, we investigate the complexation of the cationic AMP colistin with diblock copolymers poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) forming colistin-complex coacervate core micelles (colistin-C3Ms). We present long-term stable kinetically controlled colistin-C3Ms that can be prepared from several block lengths of PEO-b-PMAA polymers, where the polymerisation degree governs the overall micellar size. To achieve precise control over size and polydispersity, which are crucial for drug delivery applications, we investigate the hybridisation of PEO-b-PMAA polymers with varying chain lengths or PMAA homopolymers in ternary complex coacervation systems with colistin. This results in size-tunable colistin-C3Ms, ranging, depending on the mixing ratios, from micellar sizes of 26 nm to 100 nm. With size tunability at rather narrow size distributions and high stability, ternary colistin-C3Ms offer potential advancements in C3M drug delivery, paving the way for more effective and targeted treatments for bacterial infections in precision medicine.

The continuous synthesis of nanoparticles (NPs) has been actively studied due to its great potential to produce NPs with reproducible and controllable physicochemical properties. Here, we achieved the high throughput production of nanostructured lipid carriers (NLCs) using a coaxial turbulent jet mixer with an added heating system. This device, designed for the crossflow of precursor solution and non-solvent, combined with the heating system, efficiently dissolves solid lipids and surfactants. We reported the flow regime according to the Reynolds number (Re). Also, we confirmed the size controllability of NLCs as dependent on both Re and lipid concentration. The optimized synthesis yields NLCs around 80 nm, ideal for targeted drug delivery by enhanced permeability and retention (EPR) effect. The coaxial turbulent jet mixer enables effective mixing, producing uniform size distribution of NLCs. The NLCs prepared using the coaxial turbulent jet mixer were smaller, more uniform, and had higher drug loading compared to the NLCs synthesized by a bulk nanoprecipitation method, showcasing its potential for advancing nanomedicine.

Preclinical and clinical diagnostics depend greatly on medical imaging, which enables the identification of physiological and pathological processes in living subjects. It is often necessary to use contrast agents to complement anatomical data with functional information or to describe the disease phenotypically. Nanomaterials are used as contrast agents in many advanced bioimaging techniques and applications because of their high payload, physicochemical properties, improved sensitivity, and multimodality. Metals with k-edge energy within the X-ray bandwidth respond to photon counting and spectral X-ray imaging. This Perspective examines the progress made in the emerging area of nanoparticle-based k-edge contrast agents. These nano "k-edge" particles have been explored with spectral photon counting CT (SPCCT) for multiplexed molecular imaging, pushing the boundaries of resolution and capabilities of CT imaging. Design considerations, contrast properties, and biological behavior are discussed in detail. The key applications are highlighted by categorizing these nanomaterials based on their X-ray, k-edge energy, and biological properties, as well as their synthesis, functionalization, and characterization processes. The article delves into the transformative impact of nano "k-edge" particles on early disease detection and other biomedical applications. The review provides further insights into how the "k-edge signatures" of these nanoparticles combined with photon counting technique can be leveraged for quantitative, multicontrast imaging of diseases. We also discuss the status quo of clinically approved nanoparticles for imaging and highlight the challenges such as toxicity and clearance as well as promising clinical perspectives, providing a balanced view of the potential and limitations of these nanomaterials. Furthermore, we discuss the necessary future research efforts required to clinically translate nano "k-edge" particles as SPCCT contrast agents for early disease diagnosis and tracking.

Nanoparticle (NP)-based drug delivery systems hold immense potential for targeted therapy and diagnosis of neurological disorders, overcoming the limitations of conventional treatment modalities. This review explores the design considerations and functionalization strategies of NPs for precise targeting of the brain and central nervous system. This review discusses the challenges associated with drug delivery to the brain, including the blood-brain barrier and the complex heterogeneity of traumatic brain injury. We also examine the physicochemical properties of NPs, emphasizing the role of size, shape, and surface characteristics in their interactions with biological barriers and cellular uptake mechanisms. The review concludes by exploring the options of targeting ligands designed to augment NP affinity and retention to specific brain regions or cell types. Various targeting ligands are discussed for their ability to mimic receptor-ligand interaction, and brain-specific extracellular matrix components. Strategies to mimic viral mechanisms to increase uptake are discussed. Finally, the emergence of antibody, antibody fragments, and antibody mimicking peptides are discussed as promising targeting strategies. By integrating insights from these scientific fields, this review provides an understanding of NP-based targeting strategies for personalized medicine approaches to neurological disorders. The design considerations discussed here pave the way for the development of NP platforms with enhanced therapeutic efficacy and minimized off-target effects, ultimately advancing the field of neural engineering.

Leptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Furthermore, the predominant phenotype; solid masses or freely floating cells, has altering implications on the effectiveness of drug delivery systems. The standard of care is the intrathecal delivery of chemotherapy drugs but it is associated with increased instances of treatment-related complications, low patient compliance, and suboptimal drug distribution. An alternative involves administering the drugs systemically, after which they must traverse fluid barriers to arrive at their destination within the leptomeningeal space. However, this route is known to cause off-target effects as well as produce subtherapeutic drug concentrations at the target site within the central nervous system. The development of new drug delivery systems such as liposomal cytarabine has improved drug delivery in leptomeningeal metastatic disease, but much still needs to be done to effectively target this challenging condition. In this review, we discuss about the anatomy of leptomeninges relevant for drug penetration, the conventional and advanced drug delivery methods for LMD. We also discuss the future directions being set by different clinical trials.

In this study, we demonstrate the potential of the bornite crystal structure (Cu5FeS4) of copper iron sulfide as a second near infrared (NIR-II) photoacoustic (PA) contrast agent. Bornite exhibits comparable dose-dependent biocompatibility to copper sulfide nanoparticles in a cell viability study with HepG2 cells, while exhibiting a 10-fold increase in PA amplitude. In comparison to other benchmark contrast agents at similar mass concentrations, bornite demonstrated a 10× increase in PA amplitude compared to indocyanine green (ICG) and a 5× increase compared to gold nanorods (AuNRs). PA signal was detectable with a light pathlength greater than 5 cm in porcine tissue phantoms at bornite concentrations where in vitro cell viability was maintained. In vivo imaging of mice vasculature resulted in a 2× increase in PA amplitude compared to AuNRs. In summary, bornite is a promising NIR-II contrast agent for deep tissue PA imaging.

Metal-phenolic Networks (MPNs) are a novel class of nanomaterial developed gradually in recent years which are self-assembled by metal ions and polyphenolic ligands. Due to their environmental protection, good adhesion, and biocompatibility with green phenolic ligands, MPNs can be used as a new type of nanomaterial. They show excellent properties such as anti-inflammatory, antioxidant, antibacterial, and anticancer, and have been widely studied in the biomedical field. As one of the most common subclasses of the MPNs family, copper-based MPNs have been widely studied for drug delivery, Photodynamic Therapy (PDT), Chemo dynamic Therapy (CDT), antibacterial and anti-inflammatory, bone tissue regeneration, skin regeneration wound repair, and metal ion imaging. In this paper, the preparation strategies of different types of copper-based MPNs are reviewed. Then, the application status of copper-based MPNs in the biomedical field under different polyphenol ligands is introduced in detail. Finally, the existing problems and challenges of copper-based MPNs are discussed, as well as their future application prospects in the biomedical field.

In cellular environments, certain synthetic molecules can form nanostructures via self-assembly, impacting molecular imaging, and biomedical applications. Control over the formation of these self-assembled nanostructures in subcellular organelle is challenging. By the action of stimuli, either present in the cellular environment or applied externally, in situ generation of molecular precursors can lead to accumulation and supramolecular nanostructure formation, resulting in efficient bioimaging. Here, we summarize smart fluorophore-based ordered nanostructure preparation at specific organelles for efficient bioimaging and therapeutic application towards cancer theranostics. We also present challenges and an outlook regarding intercellular self-assembly for theranostics application. Altogether, smart nanostructured materials with fluorescence read-outs at specific subcellular compartments would be beneficial in synthetic biology and precision therapeutics.