Journal of Controlled Release最新文献

{"title":"Corrigendum to ‘A LDL-masked liposomal-doxorubicin reverses drug resistance in human cancer cells’ [Journal of Controlled Release 149(2) (2011) 196–205]","authors":"Joanna Kopecka , Ivana Campia , Paolo Olivero , Gianpiero Pescarmona , Dario Ghigo , Amalia Bosia , Chiara Riganti","doi":"10.1016/j.jconrel.2026.114675","DOIUrl":"10.1016/j.jconrel.2026.114675","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114675"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking component-level chemical structural information for AI-driven targeted nanoparticle design","authors":"Haomin Wu ,&nbsp;Yu Cheng ,&nbsp;Yuanhui Ji","doi":"10.1016/j.jconrel.2026.114704","DOIUrl":"10.1016/j.jconrel.2026.114704","url":null,"abstract":"<div><div>The structural complexity and unpredictable in vivo fate of nanoparticles pose major barriers to rational design of targeted nanoparticles. The rapidly developing artificial intelligence (AI) technology brings new opportunities to establish structure-property relationships. However, the effectiveness of AI-based prediction models is still constrained by the absence of nanoparticle compositional representation. To address this, we innovatively developed component-level image-based structural descriptors (CISD) and integrated them into the nanoparticle biodistribution prediction model. Our framework addresses several challenges in generating representations of nanoparticle compositions, such as data scarcity, poor generalizability across different nanoparticle types, and limited interpretability. Therefore, our work provides a tool that bridges the chemical structural information of nanoparticle components with representations usable by machine learning. In independent cross-domain validation, our developed predictive model significantly outperformed the traditional frameworks that rely solely on nanoparticle characteristics and biodistribution experimental parameters, with an R² increase of 0.25 and an RMSE reduction of 3.22. Leveraging SHapley Additive exPlanations (SHAP) analysis and hook functions, we disentangled multi-level structure-property relationships, with CISD enhancing tunable factors in nanoparticle design. Building upon the extracted structure-property relationships and model projections, we achieved up to a 12.66-fold enhancement in predicted biodistribution values. In the future, synergistic integration with advanced algorithms like generative AI holds promise not merely for curtailing animal experimentation, but for pioneering closed-loop inverse design systems to rationally screen a wider range of potential structures of nanoparticle components and nanoparticle physicochemical attributes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114704"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146129474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular engineering of designer diabetes therapeutics","authors":"Emily L. DeWolf,&nbsp;Bernice Webber,&nbsp;Matthew J. Webber","doi":"10.1016/j.jconrel.2026.114705","DOIUrl":"10.1016/j.jconrel.2026.114705","url":null,"abstract":"<div><div>Biologic therapies for diabetes have advanced significantly through molecular engineering strategies that optimize therapeutic stability, pharmacokinetics, and delivery. This review presents an integrated overview of design principles used to develop insulin, glucagon, amylin analogs, and GLP-1 receptor agonists, highlighting their unique physicochemical challenges and therapeutic requirements. Structural modifications—including amino acid substitutions, peptide stapling, glycosylation, and PEGylation—are discussed for their roles in enhancing stability, reducing aggregation, and extending half-life. Strategies for tuning pharmacokinetics are examined, ranging from sequence-driven solubility modulation to formulation-based depot formation and vascular binding mechanisms. Various administration routes, including oral, inhaled, and intranasal delivery, are evaluated for their potential to improve adherence and more closely mimic endogenous hormone profiles. The review also addresses the development of combination therapies and multi-receptor agonists designed to synergize complementary hormonal pathways. Finally, recent progress in glucose-responsive systems is reviewed, emphasizing molecular and materials-based approaches that enable real-time, glucose-triggered therapeutic activation. Taken together, the evolution of diabetes therapeutics exemplifies the application of core molecular design concepts in biologic drug development. The strategies outlined herein not only address the complex demands of glycemic control but also provide a broadly applicable framework for engineering next-generation protein-based therapies for applications beyond diabetes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114705"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesalamine premix-based delayed release formulation and its efficacy assessment using a 3D in-vitro gut model for inflammatory bowel disease","authors":"Sunil Kumar Sah ,&nbsp;Mamta Kumari ,&nbsp;Lohare Rahul Sanjay ,&nbsp;Makka Krupali Ashokbhai ,&nbsp;Ujjwal Gupta ,&nbsp;Subhadeep Roy ,&nbsp;Santanu Kaity","doi":"10.1016/j.jconrel.2026.114672","DOIUrl":"10.1016/j.jconrel.2026.114672","url":null,"abstract":"<div><div>Mesalamine is a widely used drug for inflammatory bowel disease (IBD) but suffers from limited solubility, permeability, and multiple formulation challenges. In this study, we tried to tune mesalamine's Biopharmaceutical Classification System (BCS) properties using premix technology to enhance its solubility and intestinal permeability, and to develop a delayed-release formulation. Mesalamine premix was prepared by the spray drying technique. Particle size analysis (PSA), solubility study, Fourier-transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and <em>in-vitro</em> dissolution study were performed to characterize the premix. The premix showed reduced particle size, higher solubility, and lower crystallinity compared to pure mesalamine. Thermal analyses confirmed improved stability, while SEM revealed spherical morphology. Epithelial and endothelial permeability studies using Caco-2, HUVEC, and heterogeneous co-culture (Caco-2/HT-29/M1 macrophage) models assessed increased permeation potential. It shows its efficacy in a pro-inflammatory (M1) macrophage-induced intestinal inflammatory condition in a heterogeneous co-culture. An <em>in-vitro</em> dissolution study of the novel mesalamine delayed-release tablet showed no drug release at 0.1 N HCl (pH 1.2), and complete drug release at pH 6.8, while marketed tablets released the drug more slowly due to the enteric coating. Thus, the formulation approach showed potential as a delayed-release mesalamine oral formulation, which can be used for drug targeting to the colon without the need for a functional coating on the tablet.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114672"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically encoded self-assembling affibody-streptavidin nanoparticles for HER2-positive cancer theranostics","authors":"Anastasiia S. Obozina ,&nbsp;Anna M. Iureva ,&nbsp;Alexandr A. Kotov ,&nbsp;Sergey M. Deyev ,&nbsp;Egor S. Korenkov ,&nbsp;Victoria O. Shipunova","doi":"10.1016/j.jconrel.2026.114679","DOIUrl":"10.1016/j.jconrel.2026.114679","url":null,"abstract":"<div><div>Targeted therapy is a revolutionary approach in cancer treatment, enabling the precise elimination of malignant cells with fewer side effects than conventional chemotherapy. Among clinically approved strategies, antibody-drug conjugates (ADCs) and immunotoxins represent a rapidly expanding class of biotherapeutics, often serving as theranostic tools when linked to diagnostic components. However, their production requires complex chemical conjugation, making it a technically and economically demanding process. Similarly, nanoparticle-based systems offer targeted delivery but usually rely on multi-step, poorly reproducible syntheses. Here, we introduce a novel type of genetically encoded self-assembling protein nanoparticles with targeting functionality. These nanometer-sized particles, which we propose to term “<strong>avisomes</strong>”, self-assemble upon refolding of a fusion protein comprising the HER2-specific affibody Z_HER2:342 and streptavidin (Z_HER2:342-Strp), combining the strengths of bioconjugates and nanoparticles while avoiding the drawbacks of chemical synthesis. Importantly, they are easily and reproducibly synthesized in <em>E. coli</em>. HER2 recognition was confirmed by flow cytometry and fluorescence microscopy. To confer cytotoxic activity, avisomes were loaded with doxorubicin (DOX), yielding Z_HER2:342-Strp-DOX nanoparticles that selectively killed HER2-overexpressing cells <em>in vitro</em>. <em>In vivo</em>, treatment with Z_HER2:342-Strp-DOX significantly suppressed the growth of HER2-positive tumors in BALB/c mice. Notably, therapy was well tolerated, with no abnormal hematological or biochemical changes, and it alleviated DOX-induced neutropenia. These findings establish avisomes as a highly promising theranostic platform for HER2-positive breast cancer. Its genetically encoded, self-assembling nature eliminates the major limitations of ADCs and synthetic nanoparticles, providing a scalable, reproducible, and cost-efficient alternative for next-generation targeted cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114679"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proimmunotoxin nanodrug targeting AIDS-associated non-Hodgkin lymphoma","authors":"Shilin Chen ,&nbsp;Tong Qi ,&nbsp;Hongxu Peng ,&nbsp;Eugene Kimura ,&nbsp;Xiang Zhang ,&nbsp;Emiko Kranz ,&nbsp;Zheng Cao ,&nbsp;Zi Wang ,&nbsp;Wenting Chen ,&nbsp;Leonardo R. Ancheta ,&nbsp;Douglas A. Lappi ,&nbsp;Pei-Yu Chiou ,&nbsp;Yunfeng Lu ,&nbsp;Tracy R. Daniels-Wells ,&nbsp;Manuel L. Penichet ,&nbsp;Jing Wen","doi":"10.1016/j.jconrel.2026.114661","DOIUrl":"10.1016/j.jconrel.2026.114661","url":null,"abstract":"<div><div>B-cell non-Hodgkin lymphoma (NHL) is the most common hematopoietic malignancy in the United States, with a notably higher incidence and aggressiveness observed in individuals infected with human immunodeficiency virus (HIV), leading to AIDS-associated NHL (AIDS-NHL). The transferrin receptor 1 (TfR1/CD71), a type II transmembrane homodimeric protein, is overexpressed on several cancers, including NHL, providing a meaningful therapeutic target. Our group developed an anti-TfR1 IgG3-avidin fusion protein, ch128.1Av, designed to deliver biotinylated therapeutic agents into cancer cells through receptor-mediated endocytosis. When coupled with biotinylated saporin 6 (b-SO6), a plant-derived protein synthesis inhibitor, the resulting ch128.1Av/b-SO6 immunotoxin is highly effective at killing malignant cells. However, toxicity to normal cells limits its systemic administration. To overcome this problem, we developed a proimmunotoxin nanodrug, named “n(ch128.1Av/b-SO6)-CXCL13”. This strategy involves encapsulating individual immunotoxins within a thin zwitterionic polymer shell, which is stabilized by peptide crosslinkers that only respond to metalloproteinase-2 (MMP-2), a tumor microenvironment-specific enzyme. The nanodrug is further conjugated with a B-cell targeting chemokine CXCL13. This design allows the proimmunotoxin to circulate safely, specifically accumulate and release encapsulated ch128.1Av/b-SO6 intratumorally in response to MMP-2. This approach not only minimizes off-target toxicity but also enhances tissue penetration by enabling choline analogues on proimmunotoxin nanodrugs to bind choline transporters expressed on tumor cells or the blood-brain barrier. Importantly, n(ch128.1Av/b-SO6)-CXCL13 demonstrated antitumor efficacy in an AIDS-associated NHL xenograft mouse model. Taken together, our results suggest that n(ch128.1Av/b-SO6)-CXCL13, or similar proimmunotoxin strategies, represents a promising therapeutic avenue for AIDS-NHL and potentially other malignancies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114661"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprinted dressing with symbiotic microbes for oxygen supply and antibacterial therapy for enhanced diabetic wound healing","authors":"Kaifeng Lin ,&nbsp;He Xu ,&nbsp;Hai Liu ,&nbsp;Hejin Jiang ,&nbsp;Hongxiang Mei ,&nbsp;Linli Jiang ,&nbsp;Zhongyang Du ,&nbsp;Weiwei Tan ,&nbsp;Xiaojie Li ,&nbsp;Jiajing Zhou ,&nbsp;Juan Li","doi":"10.1016/j.jconrel.2026.114653","DOIUrl":"10.1016/j.jconrel.2026.114653","url":null,"abstract":"<div><div>Diabetic chronic wounds exhibit delayed healing due to the high blood sugar, persistent inflammation, and bacterial infections, drawing remarkable attention worldwide. Current therapeutic approaches (e.g., surgical debridement, offloading treatment, antibiotic therapy) commonly target individual factors but fall short of modulating the complex wound microenvironment, particularly the chronic hypoxia. The symbiotic relationship between photosynthetic microorganisms and antibacterial probiotics offers a unique approach to this clinical challenge. Here, we engineer a 3D-printed bioactive microbial hydrogel (BMH) dressing by embedding <em>Chlorella zofingiensis</em> and <em>Bacillus subtilis</em> in gelatin methacryloyl as an artificial symbiotic system for modulating the diabetic wound microenvironment to promote wound healing. This BMH system demonstrates photosynthetic self‑oxygenation capability and potent antibacterial activity, thus boosting fibroblast migration and angiogenesis under hyperglycemic conditions. In diabetic rat models, BMH mitigates wound hypoxia and inflammation while enhancing vascularization and collagen deposition, thereby accelerating the healing of diabetic chronic wounds. RNA sequencing results further suggest the upregulation of genes in immune-regulation and skin-regeneration pathways. This study presents a multimodal therapeutic strategy for diabetic chronic wounds, offering insights into the design of living materials for regenerative engineering and clinical translation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114653"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrate-responsive genetically engineered probiotics locally release TNF-α nanobodies against inflammatory bowel disease","authors":"Bochuan Yuan ,&nbsp;Zhangyu Li ,&nbsp;Yuanyuan Song ,&nbsp;Yaqian Zhang ,&nbsp;Feng Zhang ,&nbsp;Ke Wang ,&nbsp;Lina Du ,&nbsp;Yiguang Jin","doi":"10.1016/j.jconrel.2026.114666","DOIUrl":"10.1016/j.jconrel.2026.114666","url":null,"abstract":"<div><div>The clinical potential of oral genetically engineered probiotics is widely recognized, which is usually distinguished by the release of expressed active molecules. However, the impact of the release mode of bacterial payloads remains unknown. Here, we propose a novel release mode, “producing and storing first, then responding and releasing”, in a genetically engineered probiotic. Inflammatory bowel disease is a typical chronic intestinal disease, where nitrate in the intestinal route is highly produced. <em>Escherichia coli</em> Nissle 1917 (EcN) was genetically engineered to highly express TNF-α nanobodies (Nb^TNF-α) for storing and releasing in response to nitrate. Two types of release systems were designed: a protein complex secretion machine, Hly system, and a φX174E-based lysis-release system. These systems were separately recombined into EcN as E5 and E7. The expression and strong anti-inflammation activity of Nb^TNF-α from <em>E. coli</em> were first confirmed. A NarX/L sensing system was tailored for nitrate, which was a typical biomarker of intestinal inflammation. Both E5 and E7 exhibited similar <em>in vitro</em> kinetics of Nb^TNF-α secretion. High anti-ulcerative colitis effects were achieved by oral administration of E5 and E7, characterized by inflammation attenuation and recovery of intestinal mucosal barriers, and the levels of Nb^TNF-α expressed by both in the intestinal tract were similar. This work provides new insights into the design of pathological environment-responsive genetically engineered probiotics against diseases.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114666"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid nanoparticles containing zwitterionic lipids versatilely enhance the efficiency of mRNA delivery","authors":"Yuichi Suzuki ,&nbsp;Yuma Yamada ,&nbsp;Hideyoshi Harashima ,&nbsp;Yusuke Sato","doi":"10.1016/j.jconrel.2026.114709","DOIUrl":"10.1016/j.jconrel.2026.114709","url":null,"abstract":"<div><div>Ionizable lipids enable lipid nanoparticles (LNPs) to deliver nucleic acids, including mRNA, to target cells. However, the efficiency of the endosomal escape of conventional LNPs remains limited to a small percentage. Lipid components that actively interact with net-neutral phospholipids in endosomal membranes and promote membrane fusion potentially enhance the efficiency of endosomal escape and further improve functional mRNA delivery. In this study, we developed a zwitterionic tri-oleoyl-Tris (zTOT) library and used it to enhance mRNA delivery by replacing the widely used helper lipid 1,2-distearoyl-<em>sn</em>-glycero-3-phosphocholine (DSPC) in LNPs with zTOT. LNPs containing TOT-15, an example of zTOT, demonstrated a 5-fold higher gene expression compared with that of DSPC-LNPs. TOT-15-LNPs composed of commercially available ionizable lipids showed enhanced gene expression compared with that of DSPC-LNPs. The TOT-15-LNPs also showed almost 100% gene knockout efficiency with no toxicity. The TOT-15 system interacts with 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine (POPC) and induces a non-lamellar structure. Pharmacokinetic calculation revealed that endosomal escape efficiency of the TOT-15-LNPs was more than 9.6%. In summary, the results of this study demonstrate that the zTOT system enhances the efficiency of both endosomal escape and functional mRNA delivery.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114709"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New-generation advanced Nano-PROTACs as potential therapeutic agents in cancer therapy","authors":"Jingjuan Zhang ,&nbsp;Yongzheng Li ,&nbsp;Huiyuan Jin ,&nbsp;Peizhen Yang ,&nbsp;Huan Min ,&nbsp;Jian Song ,&nbsp;Yingqiu Qi","doi":"10.1016/j.jconrel.2026.114673","DOIUrl":"10.1016/j.jconrel.2026.114673","url":null,"abstract":"<div><div>Proteolysis targeting chimeras (PROTACs) are catalytic degraders that eliminate pathogenic proteins via the ubiquitin-proteasome system (UPS). Building on this mechanism, nano-engineered PROTACs (Nano-PROTACs) integrate PROTACs with rationally designed nanomaterials to create an emerging therapeutic platform for cancer. This integrative approach preserves the core capability of PROTACs to precisely degrade pathogenic proteins through the UPS, and also confers multiple therapeutic advantages including enhanced tissue targeting, improved membrane permeability, and controlled drug release, thereby significantly improving cancer therapeutic efficacy while effectively reducing systemic toxicity. This review provides a comprehensive overview of recent advances in Nano-PROTACs for cancer therapy, with a particular focus on the design strategies enabled by nanomaterial-based delivery systems, along with the applications in monotherapy and synergistic therapies. In addition, the therapeutic advantages and existing challenges of Nano-PROTACs are critically discussed, while delineating their potential future clinical applications, providing critical insights to the understanding of this emerging technology and offering novel perspectives for future development of precision therapeutics.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"392 ","pages":"Article 114673"},"PeriodicalIF":11.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}