International Journal of Pharmaceutics: X最新文献

{"title":"Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review","authors":"Fengbo Liu,&nbsp;Chengxing Xia,&nbsp;Hang Yu,&nbsp;Xiaofang Yang,&nbsp;Liping Ge,&nbsp;Chunwei Ye","doi":"10.1016/j.ijpx.2025.100473","DOIUrl":"10.1016/j.ijpx.2025.100473","url":null,"abstract":"<div><div>Exosomes are secreted lipid bilayer vesicles of 30–150 nm in diameter. Their low immunogenicity, excellent biocompatibility, and inherent targeting capability make them a promising drug delivery vehicle for cancer therapeutics. However, the use of natural exosomes is still challenging for therapeutic applications, including limited targeting precision and drug-loading efficiency, necessitating engineered modification strategies to optimize their performance. To further enhance exosome targeting capacity, recent studies have explored precision delivery strategies targeting subcellular structures such as lysosomes, nuclei, mitochondria, and the endoplasmic reticulum, thereby improving exosome therapeutic potential. This review systematically summarizes the core advantages of exosomes as drug carriers, elaborates on their engineering modification methods, and highlights recent advances in strategies to improve exosomes targeting of subcellular structures to enhance antitumor efficacy. The review aims to provide a theoretical foundation and technical guidance for developing exosome-based precision therapies for cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100473"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of ultrasound and ultrasound-responsive materials in wounds: A systematic review","authors":"Jialei Luo ,&nbsp;Liwan Song ,&nbsp;Xinyi Yan ,&nbsp;Xiaolu Ma ,&nbsp;Jianqing Gao ,&nbsp;Ying Luo ,&nbsp;Gaoyi Yang","doi":"10.1016/j.ijpx.2026.100485","DOIUrl":"10.1016/j.ijpx.2026.100485","url":null,"abstract":"<div><div>Wound healing is a multifaceted biological process that is highly susceptible to disruption by numerous internal and external factors, resulting in delayed tissue repair. Recent advancements have highlighted the therapeutic potential of ultrasound, especially when integrated with emerging smart materials, which together offer promising strategies for enhancing wound care outcomes. Low- and high-intensity ultrasound (US) use mechanisms such as cavitation, acoustic streaming, and radiation forces to disrupt biofilms, improve drug permeability, and promote tissue regeneration. When combined with US-responsive materials, such as scaffolds, piezoelectric composites, microbubbles, microneedles, and flexible patches, these systems enable targeted functions, including controlled drug release, antimicrobial activity, and enhanced deep tissue penetration. These responsive materials effectively overcome the limitations of conventional wound dressings, which often suffer from poor drug bioavailability, susceptibility to infection, and a lack of personalized therapeutic capabilities. This review systematically explores 5 categories of advanced materials, with a focus on their synergistic interactions with ultrasound to enhance wound healing outcomes. By elucidating the interactions between material-US and their translational implications, this review offers new perspectives to advance the clinical development of precision-based, next-generation wound therapies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100485"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferrin-modified multicomponent liposomes encapsulating paclitaxel-loaded β-elemene microemulsion enhance therapeutic efficacy in non-small-cell lung cancer","authors":"Yunyan Chen ,&nbsp;Ziwei Zhang ,&nbsp;Rui Xiong ,&nbsp;Yuqing Cao ,&nbsp;Qian Liu","doi":"10.1016/j.ijpx.2026.100488","DOIUrl":"10.1016/j.ijpx.2026.100488","url":null,"abstract":"<div><div>To achieve efficient accumulation and facilitate profound penetration of anti-tumor agents within neoplastic tissues stands as one of the most critical determinants influencing the efficacy of anticancer therapies. Herein, a multicomponent-based liposomes (Tf-PEM/L) by transferrin-modified encapsulating paclitaxel (PTX)-loaded <em>β</em>-elemene microemulsion (PEM) was fabricated, demonstrating significantly enhanced therapeutic efficacy against non-small cell lung cancer (NSCLC). Leveraging the synergistic mechanism of transferrin-mediated active targeting coupled with the enhanced permeability and retention (EPR) effect, Tf-PEM/L demonstrates a pronounced propensity for efficient and substantial accumulation at the tumor site. Following accumulation, the subsequently released PEM enables highly efficient deep penetration within tumor tissue, thereby achieving favorable anti-tumor therapeutic efficacy. Characterization of Tf-PEM/L revealed a mean particle size approximately (144.76 ± 9.34) nm, while the zeta potential exhibited a measurement of (−12.52 ± 0.28) mV. Notably, the transmission electron microscopy (TEM) images revealed the small-sized PEM were encapsulated within large-sized liposomes. In vitro cytotoxicity assays demonstrated that Tf-PEM/L elicited synergistic antitumor effects against A549 cells, underscoring its combinatorial therapeutic potential. In vivo studies, Tf-PEM/L demonstrated exceptional tumor-targeting capabilities as evidenced by quantitative biodistribution analyses. Moreover, Tf-PEM/L exhibited superior antitumor efficacy with tumor inhibition rate of (81.36 ± 3.87)% while markedly attenuating systemic toxicity, positioning it as a promising therapeutic strategy for NSCLC. Collectively, the Tf-PEM/L represents a promising targeted therapeutic strategy for NSCLC, with enhanced efficacy and safety profiles.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100488"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prostate-specific membrane antigen targeted small molecule-drug conjugate for efficient prostate cancer therapy at a low dosage","authors":"Jingjing Zhang ,&nbsp;Fanchun Hu ,&nbsp;Caiting Deng ,&nbsp;Yuhan Ding ,&nbsp;Yuchen Yang ,&nbsp;Shupeng Han ,&nbsp;Jun Liu ,&nbsp;Feifei An ,&nbsp;Mingsong Shi","doi":"10.1016/j.ijpx.2026.100496","DOIUrl":"10.1016/j.ijpx.2026.100496","url":null,"abstract":"<div><div>Prostate-specific membrane antigen (PSMA), which is overexpressed in most prostate cancer cells, serves as an ideal target for precision therapy. The clinical utility of the potent chemotherapeutic agent SN38 is hindered by its poor water solubility and systemic toxicity. Herein, we present a novel, fully water-soluble small-molecule drug conjugate (SMDC), SN38-SS-3PEG₂₄-3PSMA (SPP), designed for enhanced prostate cancer targeting and tumor-selective drug release. SPP integrates three PSMA-targeting ligands, a glutathione (GSH)-responsive disulfide linker, and three monodisperse polyethylene glycol (PEG) chains, achieving exceptional water solubility (&gt;1 mM) and tumor-specific payload activation. In vivo fluorescence imaging revealed efficient tumor accumulation with minimal hepatic distribution, as evidenced by predominant renal clearance, thereby reducing hepatotoxicity risks. Remarkably, SPP demonstrated potent tumor growth inhibition at low doses (20 nmol) in PSMA-positive xenograft models, outperforming controls without PEG spacers or disulfide linkers. The GSH-triggered release of SN38 within the tumor cells ensured high cytotoxicity against cancer cells while maintaining stability in circulation, thereby minimizing off-target toxicity. Collectively, this study highlights SPP as a promising therapeutic candidate, combining enhanced water solubility, precise tumor targeting, and low-dose efficacy with an excellent safety profile, offering a transformative strategy for prostate cancer treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100496"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printed system using ex vivo porcine eye globes to investigate intracorneal absorption of dexpanthenol from contact lens care solution and eye drops","authors":"Verena Santer ,&nbsp;Adyl-Michaёl El Guamra ,&nbsp;Tohru Kawaguchi ,&nbsp;Mouad Lamrani ,&nbsp;Yogeshvar N. Kalia","doi":"10.1016/j.ijpx.2025.100472","DOIUrl":"10.1016/j.ijpx.2025.100472","url":null,"abstract":"<div><div>Reduction of the use of animal models in research is encouraged for the sake of animal wellbeing. However, available <em>in vitro</em> models in the specific case of topical ocular delivery/penetration studies are often oversimplified by the use of excised corneal or scleral tissue and the frequent lack of dynamic barriers such as the lacrimal outwash. This is why we have developed our novel <em>ex vivo</em> porcine eye globe 3D printed laboratory setup with simulated tear flow, using enucleated porcine eyes. This setup was employed to investigate the penetration of a common topical formulation excipient Dexpanthenol (Dxp). First, Dxp deposition in soft contact lenses following usage of SOLOCARE AQUA® care solution was quantified by UHPLC-MS/MS. The subsequent penetration into corneal tissue and aqueous humour of Dxp from SOLOCARE AQUA® care solution treated contact lenses was compared to that following application of eye drop solutions Bepanthen® and Siccaprotect®, containing equivalent Dxp concentrations. The results showed that the Dxp concentration in the anterior segment was three-fold higher after application of the Dxp-containing eye drops as compared to contact lens application. Given that Dxp uptake was greater following the application of the marketed eye drops, this confirmed the safety of the Dxp-containing contact lens care solution. This research demonstrates how topical delivery studies on the ocular surface can be simulated in our novel <em>ex vivo</em> porcine eye globe model without the need to sacrifice laboratory animals<strong>.</strong></div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100472"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro, ex vivo, and in vivo evaluation of ophthalmic ointments containing dexamethasone and tobramycin","authors":"Catheleeya Mekjaruskul ,&nbsp;Andre O'Reilly Beringhs ,&nbsp;Tuo Meng ,&nbsp;Aji Alex Moothedathu Raynold ,&nbsp;Qingguo Xu ,&nbsp;Matthew Halquist ,&nbsp;Bin Qin ,&nbsp;Yan Wang ,&nbsp;Xiuling Lu","doi":"10.1016/j.ijpx.2025.100476","DOIUrl":"10.1016/j.ijpx.2025.100476","url":null,"abstract":"<div><div>This investigation compares <em>in vitro</em> release, <em>ex vivo</em> release and permeation, and <em>in vivo</em> ocular pharmacokinetics to render biologically informed evaluations of ophthalmic semi-solid drug products containing dexamethasone (hydrophobic) and tobramycin (hydrophilic). Both drugs were formulated with three petrolatum matrices (IGI® 320 A, IGI® 386, or Spectrum®) with distinct rheological character and benchmarked against the reference listed drug, Tobradex®. Temperature-sweep rheology revealed that IGI® 386 most closely reproduced the viscoelastic profile of the reference product. USP Apparatus I release testing with surfactant-free medium provided maximal discrimination for dexamethasone (Tobradex® &gt; IGI® 320 A &gt; IGI® 386 &gt; Spectrum®), and rank-order release rates correlated strongly with <em>ex vivo</em> corneal permeation and <em>in vivo</em> corneal exposure. In contrast, tobramycin required a polysorbate-containing medium to resolve formulation differences <em>in vitro</em>, yet those differences did not persist <em>ex vivo</em> or <em>in vivo</em>, consistent with its rapid dissolution and diffusion, which attenuate matrix effects. The data demonstrate that drug solubility dictates the choice of biorelevant release conditions in petrolatum-based ophthalmic ointments: surfactant-free media capture formulation-dependent release for hydrophobic actives, whereas hydrophilic actives may yield artifactual discrimination when surfactant is present. However, formulations indistinguishable <em>in vitro</em> were typically similar in their <em>in vivo</em> ocular pharmacokinetics. By integrating tiered models, the framework enhances understanding of critical quality attributes, supports regulatory decision-making, and may help reduce reliance on animal studies, thereby expediting the development of therapeutically equivalent generic ophthalmic ointments.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100476"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double action of HPMCAS as a dry binder and precipitation inhibitor in ASD tablet formulations of nifedipine prepared by hot-melt extrusion","authors":"David S. Nakhla ,&nbsp;Saurabh M Mishra ,&nbsp;Christian Lübbert ,&nbsp;Luis Mejia ,&nbsp;Kess Agatovure ,&nbsp;Andreas Sauer","doi":"10.1016/j.ijpx.2025.100475","DOIUrl":"10.1016/j.ijpx.2025.100475","url":null,"abstract":"<div><div>Poor tablet hardness and drug re-crystallization are two common challenges of amorphous solid dispersion (ASD) formulations prepared with hot-melt extrusion (HME). In the present study, we investigated the double action of hypromellose acetate succinate (HPMCAS) as a dry binder and precipitation inhibitor when externally added to high ASD load (65 %) tablets of nifedipine (NIF). Binary ASDs of NIF were prepared using either HPMCAS or copovidone (Kollidon® VA 64, PVP-VA64) as carrier polymers. Pre-dissolving HPMCAS (AS-HF) in the dissolution medium inhibited the drug precipitation and prolonged its supersaturation state at 12.5 wt % or 100 wt % relative to NIF content in ASDs prepared with either HPMCAS (1: 2, drug: polymer), or PVP-VA64 (1: 6, drug: polymer), respectively. In contrast, pre-dissolving hydroxypropyl cellulose (Klucel™, HPC-EXF) or PVP-VA64, did not prevent the drug re-crystallization. The external addition of AS-HF (5 % <em>w</em>/w) to the ASD tablets of NIF: HPMCAS (1: 2) improved the tabletability, compressibility and compactibility of the blend, resulting in tablets with good tensile strength (1.9 MPa) vs 1.5 MPa or 0.8 MPa with either HPC-EXF (5 % w/w) or PVP-VA64 (5 % w/w), respectively. The results from this study demonstrate, for the first time, the dual function of HPMCAS (AS-HF) as a dry binder and precipitation inhibitor in high ASD load tablets, independent of the carrier polymer. This can potentially reduce the pill burden and improve the drug bioavailability in ASD tablet formulations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100475"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punicic acid ethyl ester, a superior absorption-enhancer over pomegranate seed oil, dramatically improves quercetin bioavailability via strong interaction and rapid lipolysis","authors":"Yutong Ding ,&nbsp;Jiayi Gong ,&nbsp;Ping Yang ,&nbsp;Zhengxi Zhao ,&nbsp;Zhenglu Jiang ,&nbsp;Xinru Yang ,&nbsp;Meisha Xu ,&nbsp;Xiaoqiang Guo ,&nbsp;Yun Yan ,&nbsp;Qian Yao","doi":"10.1016/j.ijpx.2026.100499","DOIUrl":"10.1016/j.ijpx.2026.100499","url":null,"abstract":"<div><div>Low oral bioavailability remains a major challenge for drug delivery. Fatty acids (FAs) and vegetable oils have attracted great interest as absorption enhancers due to their excellent compatibility. However, the difference in absorption-enhancing efficiency of various FA chemical forms and the underlying mechanisms remain unclear. In vegetable oils, FAs are confined within rigid triglyceride structures, whereas free FAs or their monoesters possess flexible carbon chains. We hypothesize that such molecular flexibility facilitates stronger drug interactions, resulting in greater absorption-enhancing capacity for FAs or their monoesters compared with parent oils. To validate this, punicic acid (PA) was isolated from pomegranate seed oil (PSO) and converted into its ethyl ester (PAEE). Employing quercetin (QU) as the model drug and oleic acid (OA) as a control, we systematically evaluated the effect of PAEE, PSO, OA, and their nanoemulsions (NE) on QU physiochemical characteristics. <em>In vitro</em>, the antibacterial activity followed the order of QU-PAEE &gt; QU-PSO &gt; QU-OA &gt; QU. Among the oils, PAEE showed strongest protection on QU in gastrointestinal fluid, the greatest interaction with QU, and significantly faster lipolysis than PSO. NE formulations further amplified these effects. <em>In vivo</em>, PAEE, PSO, and OA increased QU oral bioavailability by 4.57-, 3.49-, and 3.07- fold, respectively, whereas their NE achieved 20.66-, 6.42-, and 6.19- fold increases. This study identifies PAEE as a highly efficient and safe absorption-enhancer and, more importantly, demonstrates that FA monoesters present markedly stronger absorption-enhancing efficiency than their parent oils, providing new insights for the design of lipid-based drug carriers.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100499"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen-sparing photodynamic therapy via dissolving microneedles for rheumatoid arthritis","authors":"Lijie Zheng ,&nbsp;Yingying Li ,&nbsp;Xun Gu ,&nbsp;Xinao Chang ,&nbsp;Man Jiang ,&nbsp;Wenjun Shao ,&nbsp;Hanqing Zhao ,&nbsp;Fangyuan Chen ,&nbsp;Tao Ma ,&nbsp;Qingqing Wang","doi":"10.1016/j.ijpx.2025.100481","DOIUrl":"10.1016/j.ijpx.2025.100481","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, which leads to significant morbidity and disability. Although current therapies offer benefits to some patients, they often fail to fully address the intricate pathophysiology of RA, particularly the inflammatory proliferation and hypoxic microenvironment in synovial tissue. Herein, we propose an oxygen-sparing photodynamic therapy (PDT) strategy via dissolving microneedles (DMNs), in which both the photosensitizer and glycolysis inhibitor are simultaneously loaded into the DMNs for RA treatment. The strategy integrates PDT to target and suppress synovial hyperplasia and alleviate joint inflammation and bone damage. Additionally, an oxygen-sparing strategy was employed through glycolysis inhibition to improve the hypoxic microenvironment in RA, thereby potentiating PDT, reducing inflammatory microenvironmental factors, and promoting inflammatory cell death. In vitro results demonstrated that the combination treatment significantly increased reactive oxygen species (ROS) levels by 426.15 %, reduced ATP content by 34.78 %, and induced significant death in inflammatory synovial cells, decreasing cell viability to 14.69 %. In adjuvant arthritis (AA) rats, the treatment significantly reduced paw swelling by 20.99 %, alleviated splenomegaly by 39.62 %, and improved inflammation and related pathological changes in both synovial and ankle tissues. Furthermore, the treatment significantly reduced serum levels of pro-inflammatory cytokines, indicating a broad anti-inflammatory effect. This multifaceted approach not only enhances therapeutic efficacy for RA but also provides a theoretical basis for the development of innovative treatment formulations.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100481"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision PEGylation of ZnO quantum dots enables selective intracellular killing of Uropathogenic E. coli via multimodal antibacterial mechanisms without inducing resistance","authors":"Jingqi Niu ,&nbsp;Fangyuan Du ,&nbsp;Mingxuan Zhang ,&nbsp;Beiliang Miao ,&nbsp;Yu Hong ,&nbsp;Heyujia Yu ,&nbsp;Xiaohua Liang ,&nbsp;Mengqi Gao ,&nbsp;Qifan Chen ,&nbsp;Shiwei Liu ,&nbsp;Baoshan Liu ,&nbsp;Hongwei Xin ,&nbsp;Zeliang Chen","doi":"10.1016/j.ijpx.2025.100479","DOIUrl":"10.1016/j.ijpx.2025.100479","url":null,"abstract":"<div><div>The intracellular persistence and biofilm-forming capacity of uropathogenic <em>Escherichia coli</em> (UPEC) are major contributors to urinary tract infections (UTIs) recurrence and antibiotic failure. Here, we report a precisely engineered nanotherapeutic based on ZnO quantum dots (QDs) surface-functionalized with low-molecular-weight polyethylene glycol (PEG200), designed to enhance biocompatibility while preserving potent antibacterial activity. The optimized ZnO@PEG200 QDs exhibited excellent aqueous dispersibility, minimal cytotoxicity, and broad-spectrum efficacy against both drug-sensitive and multidrug-resistant <em>Escherichia coli</em> strains. Mechanistic studies revealed that the QDs exerted multimodal bactericidal effects, including Zn²⁺ ion release, membrane destabilization, intracellular reactive oxygen species (ROS) generation, genomic DNA fragmentation, and transcriptional repression of key virulence genes such as papG, FimH, and FliC. Notably, ZnO@PEG200 QDs disrupted bacterial motility and eradicated established biofilms even at sub-inhibitory concentrations. Long-term passaging assays demonstrated that sub-MIC exposure to ZnO@PEG200 QDs did not induce resistance development. In vivo, the QDs preferentially accumulated in the bladder and kidneys, significantly reduced intracellular bacterial burden, suppressed inflammatory cytokine expression, and promoted tissue repair in a murine UTIs model. Collectively, this work establishes ZnO@PEG200 QDs as a safe and effective nanoplatform for precision antimicrobial therapy, offering a resistance-free strategy for the treatment of intracellular and biofilm-associated bacterial infections.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"Article 100479"},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}