Wound healing is a complex process, the disruption of which can lead to infection, scarring, and chronic wounds. Natural agents such as naringenin, a flavonoid with antioxidant activity, and collagen, a structural protein with anti-inflammatory properties, can enhance wound repair. Niosomes are vesicular carriers that can improve the delivery of healing agents. In this study, a polymeric niosomal system containing naringenin and collagen was developed and its wound healing efficacy was evaluated. A 2 × 3 factorial design with 8 primary formulations was used to optimize formulation variables. Niosomes were prepared by a modified thin-film hydration method and incorporated into a topical gel. An in vivo rat excisional wound model was used to assess wound healing over 15 days. The optimized niosomes were 236.03 ± 12.80 nm with poly dispersity value of 0.45 ± 0.05. The zeta potential value was -49.50 ± 0.87 mv and entrapment efficiency of naringenin and collagen were 36.77% and 39.26% respectively. Moreover, drug loading for naringenin and collagen were 3.33% and 3.56% respectively. The optimized niosomal collagen-naringenin gel showed suitable stability and demonstrated wound healing efficacy comparable to the positive control and significantly superior to negative and sham groups (P < 0.05).
Pancreatic cancer remains a highly lethal malignancy with limited therapeutic options. Nanoparticle-based strategies hold great promise for improving treatment outcomes, yet the global research landscape and evolutionary trajectory remain unclear. We performed a comprehensive bibliometric analysis of publications from Web of Science, PubMed, and Scopus (up to July 2026) using CiteSpace, VOSviewer, and Bibliometrix. A total of 4889 publications were included, with an annual growth rate of 28.36%. China and the United States are the leading contributors, with China surpassing the USA in total citations since 2019. Top institutions include the Chinese Academy of Sciences, Zhejiang University, and Harvard University. Research hotspots have shifted from conventional drug delivery to tumor microenvironment modulation, exosome-based delivery, gene therapy, and combinatorial regimens. Nanoparticle research in pancreatic cancer has evolved into an interdisciplinary field transitioning from material design to biologically integrated multimodal strategies. Future priorities include clinical translation, standardization, and tumor microenvironment targeting.
Small interfering RNA (siRNA) therapeutics have emerged as a transformative approach for sequence-specific gene silencing, offering the potential to treat a broad spectrum of diseases by selectively suppressing disease-associated genes. However, the clinical translation of siRNA remains limited by rapid enzymatic degradation, poor cellular uptake, inadequate endosomal escape, and off-target effects, necessitating the development of efficient delivery systems. Extracellular vesicles (EVs) have gained considerable attention as natural nanocarriers owing to their excellent biocompatibility, low immunogenicity, intrinsic targeting capability, and ability to protect therapeutic cargo while traversing complex biological barriers. This review comprehensively discusses the biological characteristics of EVs, the molecular basis of RNA interference, and the major challenges associated with siRNA delivery [Fig. 1]. Recent advances in EV engineering, including cargo-loading strategies such as electroporation, sonication, extrusion, parent-cell engineering, and microfluidic approaches, together with surface functionalization using peptides, antibodies, aptamers, and hybrid nanoplatforms, are critically evaluated for improving targeting specificity and intracellular delivery. Furthermore, the therapeutic applications of engineered EV-mediated siRNA delivery in cancer, neurological disorders, liver diseases, cardiovascular diseases, inflammatory disorders, and infectious diseases are systematically summarized, highlighting their potential to enhance gene silencing while minimizing systemic toxicity. Current challenges related to large-scale manufacturing, cargo-loading efficiency, standardization, quality control, regulatory approval, and clinical translation are also discussed, together with emerging technologies involving synthetic biology, genome engineering, artificial intelligence, and multifunctional hybrid vesicles. Overall, engineered extracellular vesicles represent a highly versatile and biologically inspired platform for targeted siRNA delivery, providing a promising foundation for the development of next-generation precision RNA therapeutics and accelerating the clinical translation of gene-silencing strategies.
Quantitative detection of Golgi protein 73 (GP73), a promising biomarker for hepatocellular carcinoma (HCC), is crucial for early diagnosis. In this study, we developed a fluorescence aptasensor for sensitive and specific detection of GP73 based on fluorescence resonance energy transfer (FRET) between GP73 aptamer-functionalized nitrogen/sulfur co-doped graphene quantum dots (N, S-GQDs-GP73Apt) as the fluorescence donor and molybdenum disulfide@reduced graphene oxide (MoS2@RGO) as the fluorescence acceptor. In the absence of GP73, the fluorescence of N, S-GQDs-GP73Apt was effectively quenched by MoS2@RGO. Upon introduction of GP73, specific binding between GP73 and its aptamer triggered dissociation of the donor-acceptor complex, disrupting FRET and restoring fluorescence. Under optimized conditions, the normalized fluorescence intensity showed a good linear relationship with GP73 concentration ranging from 0.0001 to 100.0 μg/mL, with a low detection limit of 0.019 ng/mL. The aptasensor's performance was further validated using human serum samples with relative error ranging of 0.76%-3.85% and no statistically significant difference via t-test compared with ELISA results, demonstrating its potential as a reliable and cost-effective platform for early HCC diagnosis.
Cells are dynamic biomaterials that continuously modulate their mechanical properties and internal dynamics. This ability is increasingly recognized as a potential biophysical marker for diagnosing and predicting pathological states. We show that the collective intracellular dynamics of prostate cells can be characterized in a passive, non-invasive, contactless manner, using the interferometric amplification of light scattered by individual cells within a localized sensing volume. By employing phenotypically different prostate cell models, namely RWPE 1, C4-2B, and PC-3, we demonstrate that coherence-gated DLS provides distinct optical and biomechanical signatures, enabling discrimination among these cell lines while revealing intracellular dynamic profiles that align with their metastatic potential, in agreement with previous literature reports. This light scattering approach permits access to mechanical properties under physiological conditions and over a broad spectrum of frequencies, which in turn allows for a comprehensive cellular characterization beyond simple stiffness paradigms.
The journey of advanced nanomaterials, including nanocarrier-based therapeutics, has significantly transformed oncology by improving drug targeting, therapeutic delivery, biodistribution, and efficacy. However, the rapid clinical transition of emerging nanotechnology into clinical practice has introduced bioethical, regulatory, and social challenges that extend beyond the conventional biomedical paradigm. The current perspective argues that applying traditional bioethical principles, such as respect for persons, beneficence, non-maleficence, and justice, is challenged by the unique physicochemical characteristics of nanocarriers during the clinical transition from bench to bedside. Key issues discussed are informed consent, patient understanding, long-term safety, equitable accessibility, accountability, regulatory oversight, and post-marketing surveillance. In addition, the discussion proposes a co-responsibility approach in which patients, researchers, clinicians, industry regulatory authorities, and society collectively participate in the ethical transition process. Moreover, a co-evolutionary approach is suggested, in which innovation, ethics, regulation, and clinical applications will develop together.
Cancer remains a major health concern worldwide, with the need to identify better and more specific treatment measures. The concept of using metallic nanoparticles in drug delivery has attracted significant attention due to their distinct physicochemical characteristics, including surface area, size, and multifunctionality. However, their clinical use is constrained by rapid immune elimination, lack of specificity, and toxicity. To overcome these issues, metallic nanoparticles with cell-membrane-coating surfaces have become a good biomimetic platform that combines synthetic nanomaterials as well as biological activities in a single platform. These systems can be generated to have better immune evasion, long-term circulation, and better targeting because of receptor-mediated and homotypic interactions by mimicking natural cells. Additionally, stimuli-responsive controlled drug delivery increases therapeutic efficacy and decreases systemic side effects. Their effectiveness in other cancer therapies, such as photodynamic, chemodynamic, sonodynamic and immunotherapy, has been shown with greater tumour inhibition and lower toxicity in preclinical models.
Cancer stem cells (CSCs) sustain tumor initiation, therapy resistance, and relapse, yet evade durable control because they switch phenotype, enter quiescence, shelter within protective niches, resist drug efflux, and share markers with normal stem cells. Programmable CRISPR editing can disable intracellular self-renewal dependencies that antibodies and small molecules cannot reach, whereas only nanoscale carriers can confine such editing to intended cells; neither component alone solves the CSC problem. This review reframes CSC-directed CRISPR nanomedicine as an integrated design problem. We examine why target plasticity defeats static single-marker targeting; the sequential delivery checkpoints spanning blood stability, organ selection, tumor penetration, CSC recognition, endosomal escape, and productive editing; and advanced architectures including organ-selective lipid nanoparticles, biomimetic and vesicle carriers, metal-organic frameworks, and logic-gated systems. Genotoxicity, immunogenicity, incomplete depletion, manufacturing reproducibility, and absent CSC-specific clinical evidence remain limiting. Clinical viability, not imminent cure, is the realistic near-term objective.
Mānuka oil (MO) is derived from mānuka shrubs in New Zealand (NZ) and presents antimicrobial properties that may help combat antibiotic resistance. However, applications of MO are limited due to volatility, sensitivity to light and heat, and the complexity of controlled administration. We used ionic gelation to encapsulate MO and its derivative β-triketones (TK) within chitosan nanocarriers. Nanoparticles were characterised for morphology, chemical composition, encapsulation efficiency and release profile. Antimicrobial properties and biocompatibility were evaluated. Nanoparticles loaded with MO or TK were successfully synthesised with an average size of 331.5 nm (PDI 0.431) and 333.5 nm (PDI 0.503), respectively. Formulations showed positive zeta potentials, stability, high yield (1.5-1.8 g), as well as oil release over 24 h. Bactericidal effect was achieved at concentrations of 3.125-25.000 mg/ml, with no cytotoxic effect. This study has demonstrated the formulation of MO and TK nanoparticles for potential applications in wound dressing, protective coating and targeted drug delivery.
Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide; conventional insulin therapy suffers from poor oral bioavailability, enzymatic degradation, and hypoglycemia risk. We developed a dual pH- and glucose-responsive PEG-GOx@ZIF-8-Ins nanoplatform for oral insulin delivery via biomimetic co-precipitation. The optimized nanoplatform (178 ± 7.0 nm; zeta potential -26.5 ± 1.8 mV; surface area 891 m2/g) achieved 79.8 ± 2.7% encapsulation efficiency and 87.4% GOx retention. Release was minimal under gastric conditions (<10%) but reached 97.2% at 25 mM glucose, with high glucose selectivity. Cytotoxicity assays confirmed biocompatibility (IC50 > 200 μg/mL). In diabetic rats, oral bioavailability reached 7.2%, 5.5-fold higher than free insulin, with prolonged half-life, higher area under the curve (AUC), and 10-h normoglycemia without hypoglycemia. PEG-GOx@ZIF-8-Ins is a promising oral insulin delivery strategy for T2DM.
In this study, the natural active ingredient glycyrrhizic acid (GA) was used to replace traditional synthetic surfactants to construct GA-functionalized Tanshinone IIA (TSA) nanostructured lipid carriers (TSA@GA NLCs). The prepared TSA@GA NLCs had a particle size of 268.7 ± 2.3 nm and an encapsulation efficiency of 84.90 ± 5.45%. They exhibited a spherical core-shell structure, demonstrated good preliminary short-term stability, and displayed in vitro release profiles consistent with those of an oral sustained-release delivery system. In a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis, TSA@GA NLCs significantly reduced serum transaminase levels (ALT decreased from 246.90 ± 9.73 U/L in the model group to 83.82 ± 2.87 U/L, AST from 348.77 ± 7.66 U/L to 139.87 ± 4.31 U/L), and reversed levels of inflammatory factors (TNF-α from 62.57 ± 1.33 μg/L to 18.83 ± 0.73 pg/mL; IL-1β and IL-6 showed consistent trends) and oxidative stress markers (MDA decreased from 1.88 ± 0.11 nmol/mg prot to 1.25 ± 0.03 nmol/mg prot, GSH increased from 11.36 ± 0.49 nmol/mg prot to 14.70 ± 1.00 nmol/mg prot), improved histopathological damage to liver tissue, reduced collagen deposition, and suppressed α-SMA expression. The TSA@GA NLCs group demonstrated significantly better improvement across all indicators. Furthermore, this study preliminarily investigated changes in protein expression in the NRF2/NF-κB pathway; however, molecular interactions between these pathways require further validation. The findings indicate that GA possesses dual functions of structural stabilization and combination-enhanced therapy. Through an integrated "delivery-therapy" strategy, TSA@GA NLCs effectively enhanced the antifibrotic efficacy of TSA, providing new insights for the design of delivery systems for active ingredients in traditional Chinese medicine.
Inhibition of HMG-CoA reductase by rosuvastatin (RBX) hampers the synthesis of essential biosynthetic products required for cell proliferation, thereby exerting potent anti-cancer efficacy. However, low bioavailability, lack of targeting, and side effects limit clinical usage. Thus, to surpass these limitations and enable active targeting, RBX-loaded phenylboronic acid nanoconstructs (pPBA-RBX/NCs) were developed and optimized using central composite design (CCD) in Design-Expert® software. Nanoconstructs had an optimal size (182.4 ± 1.55), monodisperse nature (0.24 ± 0.05), maximum DL (39.12 ± 1.02%), and spherical shape. Due to the intrinsic property of the boronic ester, a pH-dependent sustained release was observed for 96 h. Tumor-targeting efficiency of the nanoconstructs was substantiated by cell culture studies in colon cancer cell lines, and efficacy testing in a preclinical model. Safety assessment of pPBA-RBX/NCs showed insignificant changes in the systemic biomarker levels and hemocompatibility. Overall, the developed pPBA nanoconstructs offer a novel framework for an effective and targeted delivery of therapeutics.
The convergence of synthetic biology and nanotechnology has created new opportunities for cancer diagnosis and therapy. Engineered microorganisms exhibit unique tumor-targeting, colonization, and immunomodulatory capabilities, while nanomaterials provide versatile platforms for drug delivery, imaging, and controlled therapeutic release. This review summarizes recent advances in the application of engineered microorganisms and nanomaterials in oncology, with a focus on their mechanisms of action, therapeutic potential, and translational challenges. We discuss the roles of the tumor microbiome in cancer progression, microbial engineering strategies for tumor targeting and immune regulation, and the development of nanomaterial-based delivery systems and immunotherapies. Particular attention is given to microbe-nanomaterial hybrid platforms, which combine the advantages of both systems to enhance therapeutic efficacy and modulate the tumor microenvironment. Finally, key challenges related to biosafety, biocompatibility, regulatory approval, and clinical translation are highlighted. The integration of engineered microorganisms and nanomaterials represents a promising strategy for next-generation precision oncology and may accelerate the development of more effective and personalized cancer therapies.
Polymeric mesoscale nanoparticles (MNPs) are 300 to 500 nm in diameter with a PEGylated surface that exhibit unique renal tropism as a function of that size range, as described in our prior work, with selectivity toward renal tubular epithelial cells. Despite their well-described therapeutic applications, we do not yet fully understand whether they maintain the unique mesoscale size range under various storage condition, nor do we understand the mechanisms of their internalization in renal tubular epithelial cells. Here, we investigated whether MNPs maintain their size when exposed to freeze-thaw cycles and storage outside their intended -20 °C condition. MNPs demonstrated negligible changes in size and polydispersity up to 4 freeze-thaw cycles, while we found an increase in size elevated temperature as a function of cargo loading. We then performed in vitro studies to evaluate MNP cellular uptake mechanisms using the human renal cell carcinoma tubular epithelial cell line 786-O treated with pharmacological inhibitors of uptake pathways. We found that MNP internalization is almost entirely prevented by dynamin inhibitors, while macropinocytosis inhibition also reduced uptake, suggesting that such standard nanoparticle uptake pathways are robust to the mesoscale size range.
The physicochemical properties of highly diluted homeopathic preparations remain insufficiently characterized. This study investigated particulate features of Kali carbonicum (K2CO3) at 50-millesimal potencies (LM4-LM7, ∼1:50,000 dilutions per step) and explored plasma proteomic changes in a placebo-controlled N-of-1 trial. Scanning electron microscopy showed larger particle size in Kali carbonicum (67.3 nm) than in the lactose control (47.5 nm) at LM4 in a descriptive comparison. Dynamic light scattering showed no significant differences in size, polydispersity, or zeta potential among Kali carbonicum, lactose control, and solvent blank, accounting for vial-level clustering. Atomic force microscopy showed more compact dendritic assemblies in Kali than in lactose controls, suggesting trituration influences self-organization. Raman spectroscopy of LM7 detected carbonate-associated bands absent in controls. Plasma proteomics identified six FDR-significant proteins during Kali exposure, including increased S100A9, with exploratory enrichment for inflammation, cytoskeletal, and motility terms. These findings are exploratory and do not imply causality.
Triple-negative breast cancer (TNBC) remains a formidable challenge due to its aggressive progression and the absence of established therapeutic targets. This study engineered a multifunctional, tumor microenvironment (TME)-responsive nanoplatform MnO2@Man/DOX, which was designed for synergistic targeted chemotherapy and TME modulation. The platform comprises a manganese dioxide (MnO2) core for redox regulation and a mannose (Man) shell for active targeting and metabolic sensitization, stabilized with bovine serum albumin and sodium dodecyl sulfate. MnO2@Man/DOX nanoparticles are nearly spherical (289 nm) and exhibit dual-responsiveness by efficiently depleting intracellular glutathione and catalyzing endogenous hydrogen peroxide into cytotoxic hydroxyl radicals via Fenton-like reactions. In vitro, the nanoplatform demonstrated a remarkable 8-fold reduction in IC50 (0.52 μg/mL) compared with free doxorubicin (4.2 μg/mL) in 4T1 cells. Transcriptomic analysis suggested that MnO2@Man/DOX is associated with TNF signaling and apoptosis-related pathways, including extrinsic, intrinsic, and endoplasmic reticulum stress-mediated programs. In vivo evaluations in 4T1 tumor-bearing mice confirmed preferential tumor accumulation and superior growth inhibition with a high biosafety profile, including a hemolysis rate below 5% and minimal systemic toxicity. By integrating receptor-mediated targeting, redox homeostasis disruption, and chemosensitization, MnO2@Man/DOX offers a promising metabolism-oriented strategy for treating refractory TNBC.
