Search Results (2,114)

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by significant treatment challenges and poor prognosis. Traditional therapies such as surgical resection, radiotherapy, and chemotherapy often suffer from limitations including insufficient therapeutic specificity, potential damage to normal tissues, and limited imaging capability. The integrated diag{Pareja, 2018 #13}nosis-treatment platform combines diagnostic and therapeutic functions, offering a novel approach for real-time tumor monitoring and precision therapy. Methods: Accordingly, this study designed and developed an integrated diagnostic and therapeutic platform called A₂S-TT NPs, utilizing self-assembled nanoparticles incorporating organic conjugated molecules for precise photodynamic therapy (PDT) guided by dual modalities of Near-infrared II (NIR-II) fluorescence imaging and photoacoustic imaging (PA). Results: Under 808 nm laser excitation, A₂S-TT NPs efficiently generated reactive oxygen species (ROS) at the tumor site, inducing mitochondrial membrane potential disruption and DNA damage to activate apoptosis. In vitro experiments demonstrated that A₂S-TT NPs exhibited intense NIR-II fluorescence and photoacoustic signals, showcasing excellent dual-modal imaging potential. Moreover, it demonstrated minimal cytotoxicity in the absence of light exposure but significantly enhanced tumor cell killing under laser irradiation, demonstrating superior biosafety and photodynamic efficacy. In vivo studies further confirmed that A₂S-TT NPs effectively accumulated at tumor sites, enabling visualization-based monitoring through its mediated NIR-II and PA dual-modal imaging. Additionally, A₂S-TT NPs-mediated PDT exhibited remarkable tumor-suppressive effects while avoiding significant damage to normal tissues. Discussion: This study constructs a novel PA/NIR-II dual-modal imaging-guided PDT platform based on donor–acceptor conjugated polymer A₂S-TT NPs for integrated TNBC theranostics. PA provides high-resolution deep-tissue imaging, while NIR-II fluorescence offers high sensitivity and deep penetration; their complementary strengths support precise tumor localization and real-time therapeutic monitoring. Under dual-modal guidance, A₂S-TT NPs enrich in tumors and generate abundant ROS upon 808 nm laser irradiation to boost PDT efficacy. In vitro and in vivo biosafety tests confirm its favorable biocompatibility with minimal systemic toxicity at therapeutic doses. Conclusions: In conclusion, A₂S-TT NPs achieved precise, efficient, safe, and controllable PDT through dual-mode imaging using NIR-II and PA, providing a novel strategy with clinical translation potential for the integrated diagnosis and treatment of TNBC. Full article

Background: Ovarian cancer is frequently diagnosed at an advanced stage and remains one of the most lethal gynecologic malignancies. The development of multidrug resistance (MDR) during repeated chemotherapy is a major cause of treatment failure and is often associated with increased drug efflux mediated by transporters such as P-glycoprotein (P-gp). In this study, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Soluplus^® (SOL) mixed micelles, abbreviated as TS, were developed to co-deliver apatinib (APA), a VEGFR-2 inhibitor, and etoposide (ETP), a topoisomerase II inhibitor, for MDR ovarian cancer models. The formulation was designed to improve the aqueous dispersion, cellular accumulation, and antitumor activity of APA and ETP. Methods: APA/ETP-loaded TS micelles (APA/ETP-mTS) were prepared and characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), storage stability, and in vitro drug release. Anticancer efficacy was assessed using MTT assays, cellular uptake assays, and 3D tumor spheroid studies employing HeyA8-MDR cells, followed by in vivo toxicity and antitumor efficacy studies. Micellar formulations were denoted using the cargo–carrier format, where APA/ETP indicates co-loaded APA and ETP, C6 indicates coumarin-6 (C6) used as a fluorescent probe, mTS indicates TPGS/SOL mixed micelles, and mSOL indicates SOL-only micelles. Results: The selected APA/ETP-mTS formulation showed a particle size of 20.0 ± 5.1 nm, a PDI of 0.16 ± 0.05, near-neutral zeta potential, and encapsulation efficiencies exceeding 60% for both drugs. The micelles maintained colloidal stability at 4 °C for 4 weeks, although partial decreases in encapsulation efficiency were observed. Compared with APA/ETP solution, APA/ETP-mTS delayed the release of both drugs. C6-mTS showed higher intracellular fluorescence intensity than C6-mSOL, suggesting enhanced cellular accumulation associated with TPGS incorporation. APA/ETP-mTS showed greater cytotoxicity than free drugs in HeyA8-MDR monolayer cells and produced the strongest spheroid growth inhibition among the tested micellar formulations. In the HeyA8-MDR xenograft model, APA/ETP-mTS suppressed tumor growth and resulted in the lowest final tumor weight without apparent overt toxicity based on body weight and survival observations. Conclusions: These results suggest that APA/ETP-mTS is a promising micellar co-delivery platform for hydrophobic anticancer drugs in MDR ovarian cancer. Full article

Background: Chronic ulcers are a major healthcare challenge due to their prolonged course, recurrence, persistent microbial colonization, and impaired tissue repair. This study developed sodium alginate–collagen hydrogel dressings reinforced with cotton fabric and functionalized with green-synthesized copper oxide nanoparticles (CuO NPs) to combine exudate absorption with localized antibacterial activity. Methods: CuO NPs were synthesized using gallic acid and orange peel extract and evaluated for cytotoxicity and antibacterial activity against Staphylococcus aureus and Escherichia coli. Sodium alginate–collagen dressings containing different glycerin concentrations were assessed for swelling capacity, morphology, structural stability, and tensile performance. The formulation showing the best overall physicochemical and mechanical performance was selected for CuO NP functionalization and antibacterial evaluation by agar diffusion. Results: The selected 50GS-NPs-CuO formulation showed an IC50 of 79.9 µg/mL. At 70 µg/mL, CuO NPs produced significant time-dependent reductions in bacterial viability, reaching 96.6% for S. aureus and 91.44% for E. coli after 72 h. The dressing containing 2% sodium alginate, 0.5% collagen, and 2.5% glycerin exhibited the highest swelling capacity (476.82 ± 3.80%) and tensile strength (148.7 ± 5.5 N). CuO-functionalized dressings showed concentration-dependent antibacterial activity, with consistently greater inhibition against S. aureus than E. coli. Conclusions: The developed dressing integrates high fluid absorption, mechanical stability, and localized antibacterial activity, providing a promising platform for advanced chronic-wound management. Full article

Background: Although intracellular delivery via endocytosis is a promising strategy for drugs acting in the cytosol or nucleus, many macromolecular therapeutics remain trapped within endosomal/lysosomal compartments, limiting efficient cytosolic delivery. In this study, we designed a novel functional hyaluronic acid (HA)-based polymer, HA–octahistidine (His8), by conjugating His8 to CD44-targeting HA, and evaluated its physicochemical properties, cellular uptake, and endosomal escape capability. Methods: HA–His8 was synthesized via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS)-mediated coupling and characterized using ¹H NMR spectroscopy. Particle size and zeta potential were measured via dynamic light scattering, and buffering capacity was evaluated using acid–base titration. Cellular uptake and intracellular localization were investigated in CD44-high MDA-MB-231 and CD44-low MCF-7 cells via confocal laser scanning microscopy. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Successful conjugation of His8 was confirmed with a degree of substitution of 4.66 mol% relative to HA carboxyl groups. HA–His8 exhibited a nanoscale hydrodynamic diameter under physiological conditions, which increased under acidic conditions together with changes in zeta potential. HA–His8 exhibited higher buffering capacity than free His8 and was preferentially internalized by CD44-high MDA-MB-231 cells compared with MCF-7 cells. Compared with unmodified HA, HA–His8 exhibited lower colocalization with LysoTracker that decreased over time, indicating reduced retention within acidic vesicles. HA–His8 also exhibited low cytotoxicity over the tested concentration range. Conclusions: His8 modification alters HA intracellular localization while preserving CD44 targeting, thereby facilitating endosomal escape. These findings highlight HA–His8 as a potential platform for the cytosolic delivery of macromolecular therapeutics, including proteins, peptides, and nucleic acids. Full article

Antimicrobial resistance (AMR) presents a global health challenge that is projected to cause nearly 2 million deaths annually by 2050. With a growing ageing population and the rise of antibiotic-resistant strains globally, developing effective alternatives to combat infections while reducing AMR risks is critical. Over recent decades, antibiotic-free strategies have emerged as promising approaches, offering advantages over traditional antibiotics and reducing the likelihood of resistance. This review highlights antibiotic-free antimicrobial strategies for applications in chronic wound care, hard tissue repair, personal protective equipment, as well as hospital hygiene and infection control. We begin by outlining the broader AMR problem and then examine natural strategies—including the use of agents such as manuka honey—followed by synthetic approaches involving nanomaterials and metal–organic frameworks (MOFs), as well as biological and bioinspired antimicrobial strategies, involving antimicrobial peptides, antibodies, bacteriophages, extracellular vesicles, and macrocycles. Finally, we discuss innovations in artificial intelligence (AI)-assisted antimicrobial development and stimulus-responsive materials, before introducing a conceptual design framework for antibiotic-free antimicrobial materials. This review provides a comprehensive assessment of emerging antibiotic-free strategies to guide the development of next-generation antimicrobial solutions that reduce reliance on antibiotics and mitigate AMR in clinical and healthcare settings. Full article

Background/Objectives: Repurposing existing drugs may represent a promising strategy for effective cancer therapy. This study was the first to investigate the augmented antitumor therapeutic effect achieved by co-incorporating the NSAID Niflumic acid (NIF) with ceramides into PEGylated cerosomes (NIF-loaded PEG-CERs) in a novel platform that targets specifically the MAPK-ERK signaling pathway and miR-21-5p modulation. Methods: The prepared formulae were statistically optimized utilizing a full factorial design and the optimal formula (C5) was further incorporated into a topical gel and evaluated for ex vivo rat skin permeation, and tested in vivo in a subcutaneous solid Ehrlich carcinoma (SEC) mice model. Results: The optimal formula (C5) showed tubular elongated morphology with higher EE% (96.71 ± 0.0), lower vesicular size (VS) and PDI values, 292.95 ± 0.78 nm and 0.47 ± 0.0 respectively. A high ZP value (−37.5 ± 0.57 mV) was in accordance with stability results showing good stability of the optimal formula (C5). Permeability studies exhibited 2.02-fold higher skin permeation compared to pure NIF gel. A significant decrease in tumor volume and marked improvement in survival rate in SEC mice were confirmed by downregulation of EGFR, ERK1, ERK2, and miR-21-5p expression. Furthermore, an increase in total antioxidant capacity and caspase-3 levels was observed, accompanied by significant suppression in cyclin D1, MMP-2, COX-2, and MDA levels. Finally, histopathological analysis revealed the superior antitumor effect of C5 gel together with immunohistochemical assay showing the lowest BCL-2-positive staining, indicating the restoration of physiological apoptotic balance. Conclusions: Based on the previous findings, NIF-loaded PEG-CERs offer augmented therapeutic potential for efficient topical skin cancer management in an SEC mice model. Full article

Background/Objectives: Peritoneal dissemination of malignancies leads to poor prognoses, and no effective treatment currently exists. The difficulty of treating such malignancies is likely because systemically administered drugs cannot easily target malignant cells in the abdominal cavity. High intraperitoneal drug retention, non-toxicity towards normal tissues, and successful targeting of malignant cells are important for an effective therapy. The aim of this study was to evaluate an intraperitoneally administered astatine-labeled, integrin-targeted nanodrug, mPEG(Mn:350)-S-AuNP[²¹¹At]-c[RGDfK(C)] ([²¹¹At]AuNP@PEG/RGD), with respect to its kinetics, therapeutic efficacy, and safety. Methods: C6 rat glioma cells (10⁷), and BxPC3 (10⁷) and PANC-1 (10⁷) human pancreatic cancer cells were seeded intraperitoneally into nude mice, and [²¹¹At]AuNP@PEG/RGD (0.979 ± 0.194 MBq for C6 models (n = 3), 1.139 ± 0.035 MBq for BxPC3 models (n = 10), and 1.308 ± 0.039 MBq for PANC-1 models (n = 10) per mouse) or saline were intraperitoneally administered 4–7 days later. Cytotoxicity against malignant cells, pharmacokinetics after administration, therapeutic efficacy, and safety in abdominal organs were evaluated. Results: Intraperitoneally administered [²¹¹At]AuNP@PEG/RGD accumulated exclusively in the peritoneal cavity for a long period of time and showed minimal systemic diffusion through the blood. In the C6 model, the intraperitoneal tumor mass was significantly lower in the treated group compared with that of the controls (p = 0.05). For the BxPC3 (median survival time: control/treated = 41/65 days, p < 0.001) and PANC-1 (median survival time: control/treated = 19/35 days, p < 0.001) peritoneal dissemination models, survival analysis revealed that [²¹¹At]AuNP@PEG/RGD significantly prolonged overall survival. Although transient weight loss, leukopenia, and thrombocytopenia were observed at one week post-administration, a short recovery trend was evident thereafter. One month after administration, no abnormalities were found in hematological tests or histological analyses of intra-abdominal organs. Conclusions: The intraperitoneal administration of astatine-labeled integrin-targeted [²¹¹At]AuNP@PEG/RGD nanoparticles showed promising findings in terms of safety and efficacy for treating peritoneally disseminated malignant tumors. Full article

Background: Breast cancer remains the most common malignant tumor among women worldwide. Although conventional treatments including surgery, chemotherapy, and radiotherapy are effective, they are confronted with challenges such as tumor heterogeneity, systemic toxicity, and recurrence driven by drug resistance. To overcome these limitations, natural products have emerged as promising therapeutic alternatives owing to their multi-target efficacy and favorable biocompatibility. However, their clinical translation is still hindered by poor chemical stability, low aqueous solubility, and inadequate bioavailability. Nanodelivery systems offer a transformative solution by enhancing bioavailability and enabling precision targeting through the enhanced permeation and retention effect, thereby widening the therapeutic window and minimizing off-target toxicity. Purpose: This review evaluates diverse nanoparticle-based delivery systems and their targeting mechanisms in natural product-based breast cancer therapy. By examining inherent advantages and translational challenges, this analysis provides critical insights into the clinical development and application of these nanoformulations. Methods: A systematic literature search was performed in PubMed, ScienceDirect, Springer, Taylor & Francis, and Web of Science to identify relevant studies on natural product-based nanoformulations for breast cancer therapy. Results: Natural products exert anti-breast cancer effects through mechanisms such as inducing apoptosis, arresting the cell cycle, inhibiting invasion and metastasis, suppressing angiogenesis, and regulating autophagy. To overcome clinical hurdles, three complementary targeting strategies have been developed: passive, active, and stimuli-responsive targeting. These advances are shifting nanomedicines toward active precision therapy, markedly improving the therapeutic index. With multiple formulations already approved or in clinical pipelines, this field is rapidly progressing from laboratory research to clinical implementation. Conclusions: Natural products possess potent anti-breast cancer effects, and the application of nanodelivery technology effectively overcomes their inherent limitations of poor stability and low bioavailability. Although preliminary findings are promising, large-scale, randomized controlled clinical trials are urgently needed to systematically evaluate their safety, efficacy, and practical potential for clinical translation in breast cancer management. Full article

Targeted protein degradation (TPD) represents a whole new paradigm in cell-level therapeutic design, with its ability to remove target proteins, normally through the endogenous proteasomal, lysosomal, or autophagic systems, rather than the traditional occupancy-driven inhibition approach. But the clinical efficacy of degraders is becoming more restricted based on delivery rather than efficacy only. Many proteolysis-targeting chimeras and new proximity-inducing systems have low solubility, are impermeable, are pharmacodynamically complicated, lack tissue selectivity, and cannot fully access the intracellular space. Nanomedicine and PD platforms could provide strategies not only to overcome these challenges, but also to provide other advantages, including enhancing exposure to degraders, biodistribution, controlled release, and context-dependent activation. This critical review is an outline of all lipid, polymeric, inorganic, biomimetic, targeted, activatable, and self-assembling delivery systems for TPD. We assess compositional considerations, in vitro and in vivo evidence, challenges for translation, and clinical endpoints required to support delivery-enabled degradation. Trusted TPD therapeutics need to relate different aspects of their design, such as degrader chemistry, carrier structure, disease biology, and pharmacodynamic biomarkers, to one another. Further investigations are needed to establish intact delivery of the degrader to the target, target depletion in relevant tissues, prolonged pharmacodynamics, favorable safety, and compelling therapeutic benefit relative to free degraders or traditional inhibitors. Thus, it is important to view delivery not simply as an additional step during formulation but as a design principle necessary for the reliable clinical outcome of degradation medicine. Full article

Although oral peptide drug administration is the most desirable for both patients and healthcare systems, it is a major pharmaceutical challenge. Typically, less than 1% of orally administered peptide therapeutics reaches the systemic circulation. Modern research has focused on overcoming the physiological barriers responsible for the poor peptide drug bioavailability, while little attention has been given to understanding how measurable absorption occurs despite the barriers. This review aimed to explore the physiological factors that influence oral peptide absorption, such as enzymatic degradation and pH effects, motility, microbiota, transporters, tight junctions, and the effect of inflammation. The available data indicate that these factors function not only as barriers but may also create limited opportunities for peptide uptake. Enzymatic degradation and microbial metabolism reduce the availability of intact peptide drugs yet may generate biologically relevant fragments. Tight junctions are generally regarded as restrictive barriers but are shown to exhibit dynamic regulations that may permit transient paracellular transport. Similarly, gastrointestinal motility, microbiota, and inflammatory processes influence epithelial permeability and duration of peptide exposure both to absorptive surfaces and to degradative enzymes. In contrast, transporter-mediated uptake appears unlikely to account for the absorption of intact peptide drugs due to their substrate size limitations. Together, the findings suggest that measurable oral peptide absorption is unlikely to result from a single dominant pathway but rather from the cumulative contribution of the mechanisms. Improved understanding of these endogenous mechanisms may open opportunities to enhance oral peptide bioavailability and support the development of more effective therapeutics. Full article

Introduction: Acute lung injury (ALI) is characterized by severe inflammation and oxidative stress. However, effective pharmacological interventions for ALI remain limited. Carnosine, an endogenous dipeptide known for its redox-regulating and immunomodulatory activities, has demonstrated promising protective effects. In the present study, inhalable carnosine-loaded liposomes (Cn-Ls) were developed to enhance pulmonary delivery and achieve localized treatment in a lipopolysaccharide (LPS)-induced ALI model in mice. Methods: Cn-Ls were prepared and systematically evaluated for their morphology, stability, drug-loading capacity, and release kinetics. In vitro assays were performed to evaluate their cytocompatibility, antioxidant activity, and effects on LPS-induced reactive oxygen species (ROS) generation. In an ALI model, inhaled Cn-Ls were administered to assess pulmonary retention and therapeutic efficacy, including lung inflammation, oxidative stress, circulating levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, lung architecture, and respiratory function. Results: Encapsulation of carnosine within liposomes markedly prolonged its pulmonary retention (t₁/₂ = 1.7 h vs. 1.0 h for free carnosine), providing a more sustained lung-retentive delivery profile for up to 12 h. In vitro assays showed that Cn-Ls had excellent cytocompatibility, reduced cell death, exhibited potent antioxidant activity, and effectively suppressed LPS-induced ROS generation. In an ALI model, inhaled Cn-Ls markedly mitigated lung inflammation and oxidative stress, reduced circulating levels of CRP, TNF-α, and IL-6, preserved lung architecture, and improved respiratory function. Compared with free carnosine, Cn-Ls exhibited enhanced pulmonary retention and superior therapeutic efficacy. Conclusions: These results identified inhalable Cn-Ls as a potential nanotherapeutic approach for targeted ALI management and provided a foundation for further translational development. However, additional investigations are required to assess the long-term safety of Cn-Ls, optimize formulation stability and scalability, and further elucidate the underlying therapeutic mechanisms before clinical translation. Full article

Background/Objectives: RNA interference (RNAi) represents a promising therapeutic approach for silencing oncogenes involved in cancer progression by utilizing small interfering RNA (siRNA). However, siRNA requires an efficient delivery system to overcome cellular uptake and endosomal escape barriers. This study aimed to evaluate a multifunctional tandem peptide, GE11-599, designed to enhance the targeted delivery of siRNA and maintain its bioactivity in glioblastoma (GBM) cells. Methods: The GE11-599 peptide, consisting of an EGFR-targeting GE11 motif and a 599 fusogenic domain, was complexed with siRNA via electrostatic interactions to form nanoparticles. We assessed nanoparticle physicochemical properties, protection of siRNA from serum and RNase degradation, and cellular uptake in two GBM cell lines (U118MG and U87MG). Mechanistic studies evaluated receptor-mediated endocytosis and the subsequent escape from endosomes. Functional assays quantified STAT3 gene silencing and downstream effects on cell migration following treatment with GE11-599–siSTAT3 complexes. Results: GE11-599 formed positively charged, monodisperse nanoparticles capable of protecting siRNA from degradation. The tandem peptide significantly enhanced cellular internalization through EGFR-mediated endocytosis and facilitated endosomal escape of siRNA. Treatment with GE11-599–siSTAT3 resulted in robust gene silencing, achieving up to an 80% reduction in STAT3 mRNA expression. Downstream functional assessment showed a 40% decrease in migration in GBM cells treated with GE11-599–siSTAT3 complexes. Conclusions: The GE11-599 tandem peptide effectively enhances cell-specific internalization and endosomal escape of siRNA in GBM cells, resulting in increased siRNA bioactivity and functional gene silencing. These findings support GE11-599 as a promising siRNA delivery platform for targeting EGFR-expressing cancers. Full article

Background: Methotrexate (MTX) is a well-established therapeutic agent for psoriasis owing to its anti-inflammatory and immunomodulatory effects. However, its clinical use is limited by insufficient local accumulation in skin lesions and the potential risk of systemic exposure. Dunaliella salina-derived exosome (DsEXO) has favorable biocompatibility, low immunogenicity and potential skin delivery capacity, making it a promising natural nanocarrier for topical MTX delivery. This study aimed to construct Dunaliella salina-derived exosome loaded with methotrexate (DsEXO@MTX) and evaluate its therapeutic efficacy and potential mechanisms in psoriasis-like skin inflammation. Methods: DsEXO@MTX was prepared and characterized in terms of morphology, particle size, surface charge and drug-loading capacity. Cellular uptake, skin retention and tissue distribution were evaluated using fluorescence imaging and skin section analysis. Therapeutic efficacy was evaluated in an imiquimod-induced psoriasis-like mouse model by clinical scoring, histopathological examination, spleen index measurement and Ki-67 immunofluorescence staining. STAT3 phosphorylation and Th17/Treg differentiation were further examined to explore the potential immunomodulatory mechanism. Results: DsEXO@MTX exhibited a relatively uniform particle size distribution and drug-loading capacity. In vivo fluorescence imaging and skin section analysis showed that DsEXO@MTX enhanced local skin retention and promoted fluorescence distribution in epidermal and dermal regions. It significantly alleviated IMQ-induced erythema, scaling, epidermal thickening, inflammatory infiltration, splenomegaly and abnormal keratinocyte proliferation in psoriasis-like mice. Mechanistically, DsEXO@MTX reduced STAT3 phosphorylation and modulated Th17/Treg differentiation, suggesting restoration of immune balance in psoriatic inflammation. Conclusions: DsEXO@MTX represents a natural exosome-like nanovesicle-mediated topical MTX delivery system that improves local drug delivery and enhances therapeutic efficacy in IMQ-induced psoriasis-like skin inflammation, particularly when administered topically. These findings provide a potential strategy for safer and more efficient local treatment of psoriasis. Full article

Background: Hypertensive disorders of pregnancy present a major global health challenge. Green nanotechnology offers a strategy to enhance the stability and efficacy of bioactive natural products. This study evaluated gold nanoparticles green-synthesized with Pfaffia glomerata extract (AuNPs-PG) against gestational hypertension and fetal complications in spontaneously hypertensive rats (SHRs). Methods: P. glomerata root extract was characterized by UHPLC-MS/MS. AuNPs-PG were green-synthesized with 2 mmol/L HAuCl₄ (1:5 v/v) at 40 °C and characterized by UV-Vis and DLS. Pregnant Wistar-Kyoto and SHRs were divided into naive, negative control (NC), amlodipine (5 mg/kg), and AuNPs-PG groups (0.03, 0.1, and 0.3 mg/kg) treated daily on gestational days 1–18 to evaluate maternal cardiovascular, renal, biochemical, and reproductive outcomes. Results: UHPLC-MS/MS identified 38 compounds. AuNPs-PG showed a plasmon band at 520–550 nm and 88.1 nm hydrodynamic diameter. In SHRs, 0.3 mg/kg AuNPs-PG reduced systolic blood pressure by 18.5% and mean arterial pressure by 15.4%, while mitigating vascular dysfunction by lowering phenylephrine vasoconstriction by 52.7% and boosting acetylcholine vasodilation by 239.3%. Treatment shortened QTc interval by 26.4%, normalized T-wave inversion, and restored renal excretion, increasing urinary volume by 75.0% and sodium by 94.2%. Furthermore, AuNPs-PG elevated placental growth factor by 180.9%, lowered malondialdehyde by 63.5%, and preserved placental histology. Consequently, mean fetal weight increased by 21.6%, implantation index by 50.5%, and offspring-to-mother ratio by 129.6%. Conclusions: AuNPs-PG (0.3 mg/kg) effectively mitigate maternal and fetal complications in gestational hypertension. Gold nanoparticles serve as nanocarriers, whereas surface-adsorbed phytochemicals drive the biological effects. Full article