Journal of Controlled Release最新文献_第9页

Targeting and exploiting macropinocytosis in cancer therapy 巨红细胞增多症在癌症治疗中的靶向和利用

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-16 DOI: 10.1016/j.jconrel.2025.113962

Hye-ran Moon , Bo Kyung Cho , Seung Hyun Kang , Ju Hee Ryu , Ick Chan Kwon

{"title":"Targeting and exploiting macropinocytosis in cancer therapy","authors":"Hye-ran Moon , Bo Kyung Cho , Seung Hyun Kang , Ju Hee Ryu , Ick Chan Kwon","doi":"10.1016/j.jconrel.2025.113962","DOIUrl":"10.1016/j.jconrel.2025.113962","url":null,"abstract":"<div><div>Macropinocytosis, a cellular process often hyperactivated in cancers with KRAS mutations or PTEN deficiencies, plays a crucial role in tumor survival and therapy. While inhibiting this pathway has been explored as a strategy to deprive cancer cells of essential nutrients, recent advances in nanotechnology offer an innovative approach that exploits macropinocytosis for selective drug delivery. Engineered therapeutics, including nanoparticles, peptide-drug conjugates, and macromolecule-bound drugs, leverage the elevated macropinocytic activity in tumor cells to enhance drug uptake, thereby improving treatment efficacy while minimizing off-target effects. This review provides a comprehensive examination of the molecular mechanisms regulating macropinocytosis in cancer, addressing both intrinsic factors, such as oncogenic mutations, and extrinsic influences from the tumor microenvironment. We explore both inhibition strategies and therapeutic exploitation of macropinocytosis in cancer therapy, focusing specifically on the latest innovations in engineered therapeutics designed to enhance selective drug delivery. By addressing the challenges of translating macropinocytosis-targeting therapies into clinical practice, including tumor heterogeneity and drug resistance, this review highlights how modulating macropinocytosis presents new opportunities for more effective and personalized cancer treatments.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 113962"},"PeriodicalIF":10.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305169","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}

引用次数: 0

Dual-barrier traversing liposomes with ROS-responsive rigidity tuning for oral ischemic stroke therapy 双屏障穿越脂质体与ros反应刚性调节口服缺血性脑卒中治疗

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-15 DOI: 10.1016/j.jconrel.2025.113955

Jinjie Zhang , Jieke Zhang , Shuo Zhang , Weijing Yang , Wenhui Yang , Jun Guo , Bingxin Sun , Lulu Lv , Jianbo Li

{"title":"Dual-barrier traversing liposomes with ROS-responsive rigidity tuning for oral ischemic stroke therapy","authors":"Jinjie Zhang , Jieke Zhang , Shuo Zhang , Weijing Yang , Wenhui Yang , Jun Guo , Bingxin Sun , Lulu Lv , Jianbo Li","doi":"10.1016/j.jconrel.2025.113955","DOIUrl":"10.1016/j.jconrel.2025.113955","url":null,"abstract":"<div><div>For sustained ischemic stroke intervention, oral delivery remains optimal. However, conventional nanocarriers like liposomes fail to overcome both the intestinal epithelial (IEB) and blood-brain barriers (BBB). We engineered dual-functional, butylphthalide (NBP)-loaded liposomes (C-NBP Lip) via amphiphilic cytidine-lipoic acid conjugate (LA-C) functionalization, establishing the first unified nanoplatform for nucleoside transporter-mediated targeting and reactive oxygen species (ROS)-responsive membrane modulation. Our strategy exploits cytidine's dual affinity for apical concentrative (CNT1) and basolateral equilibrative (ENT1) nucleoside transporters on gut epithelia, enabling efficient intestinal translocation and subsequent ENT1-mediated BBB transcytosis via a single ligand. Crucially, hydrophobic interactions between LA-C's dithiolane ring and phospholipids dynamically tuned membrane rigidity of C-NBP Lip. enabling ROS-triggered drug release at ischemic lesions. In rats, C-NBP Lip exhibited 44.61 % oral bioavailability, 137 % higher than free NBP (18.80 %), and demonstrated robust neuroprotection without toxicity in both short- and long-term rat ischemic stroke model. This work pioneers “barrier-adaptive liposomes” that integrate endogenous transporter exploitation with stimulus-responsive membrane engineering for transformative oral brain delivery.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 113955"},"PeriodicalIF":10.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290045","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}

引用次数: 0

Syngeneic CAR T cells engineered for persistent delivery of desired proteins 用于持续递送所需蛋白质的同源CAR - T细胞

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-06-14 DOI: 10.1016/j.jconrel.2025.113960

Sherri L. Newmyer, Harikrishnan Radhakrishnan, Harold S. Javitz, Parijat Bhatnagar

{"title":"Syngeneic CAR T cells engineered for persistent delivery of desired proteins","authors":"Sherri L. Newmyer, Harikrishnan Radhakrishnan, Harold S. Javitz, Parijat Bhatnagar","doi":"10.1016/j.jconrel.2025.113960","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.113960","url":null,"abstract":"AbstractMouse primary T cells have been engineered as a platform using chimeric antigen receptors (CARs) to induce the synthesis of desired proteins at the disease site. This approach allows for the use of immunocompetent syngeneic tumor models to evaluate the CAR T cells' function within the context of a fully functioning immune system. Current efforts to evaluate cell-based technologies typically rely on xenograft tumor models in immunodeficient mice, which provide early feasibility data but may not fully capture the immune effects present in the tumor microenvironment. In this study, a primary T-cell-based system for site-specific protein expression has been translated from human T cells to mouse T cells, allowing for the use of an immunocompetent syngeneic tumor model. A lentivector transduction, effective in human T cells, was adapted to engineer mouse T cells. CD4 and CD8 CAR T cell subsets were engineered separately and evaluated in immunocompetent mice for site-specific expression of the desired proteins. Co-expression of membrane-bound interleukin 15 (mbIL15) on the T cells enhanced intratumoral accumulation of both CD4 and CD8 CAR T cells and supported their delivery function. Validation of this platform in syngeneic models will enable efficacy assessments beyond solid tumors and allow for the evaluation of immune-related toxicities arising from interactions between the therapeutic protein, CAR T cells, and the host immune system.”","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"32 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288378","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}

引用次数: 0

Posttranslational remodeling micelle reverses cell-surface and exosomal PD-L1 immunosuppression in tumors resistant to PD-L1 antibody therapy 在PD-L1抗体治疗耐药的肿瘤中，翻译后重塑胶束逆转细胞表面和外泌体PD-L1免疫抑制

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-14 DOI: 10.1016/j.jconrel.2025.113961

Xue Shi , Xiejun Zhao , Yinli He , Linpei Zhang , Xinmin Zheng , Xiangchuan Qin , Kefeng Li , Jing Li , Yawen Wang , Liangliang Dai , Xiaojiao Li

{"title":"Posttranslational remodeling micelle reverses cell-surface and exosomal PD-L1 immunosuppression in tumors resistant to PD-L1 antibody therapy","authors":"Xue Shi , Xiejun Zhao , Yinli He , Linpei Zhang , Xinmin Zheng , Xiangchuan Qin , Kefeng Li , Jing Li , Yawen Wang , Liangliang Dai , Xiaojiao Li","doi":"10.1016/j.jconrel.2025.113961","DOIUrl":"10.1016/j.jconrel.2025.113961","url":null,"abstract":"<div><div>Sustained replenishment of cell-surface and exosomal PD-L1 has been believed as the most important factor in the progression of PD-L1 antibody therapy resistance. Given that direct genetic blockade of PD-L1 may lead to unintended consequences and that posttranslational modifications (PTMs) are often used as pharmacological targets of cancer therapy, approaches targeting PD-L1 PTMs show great potential as new therapeutic paradigms. Palmitoylation has emerged as a critical PTM for modulating PD-L1 stability and distribution. In this work, it is found that disruption of palmitoylation by 2-bromopalmitate (2-BP) dual-impaired PD-L1 on the cell surface and exosomes. An amphiphilic TME-responsive micelle was fabricated to efficiently deliver 2-BP and the chemotherapeutic agent cisplatin to tumor milieu. The composite formulation unifying elimination of cell-surface and exosomal PD-L1 with chemotherapy synergistically relieved immunosuppression in the tumor bed and draining lymph node, thereby dramatically restraining growth, postsurgical relapse, and metastasis in melanoma resistant to PD-L1 antibody therapy. Moreover, the formulation elicits potent T cell memory responses for long-term protection against tumor rechallenge. In summary, our study takes advantage of an amphiphilic nanoformula combination of a posttranslational modifier and chemotherapy to target tumors resistant to PD-L1 antibody therapy, and paves a new path for multimodal cancer treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113961"},"PeriodicalIF":10.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288377","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}

引用次数: 0

Oral delivery of tunable oxidation-responsive budesonide-loaded nanoparticles enhances inflammation modulation in intestinal colitis 口服可调氧化反应布地奈德负载纳米颗粒增强肠结肠炎的炎症调节

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-11 DOI: 10.1016/j.jconrel.2025.113948

Cecília Cristelo , Juliana Viegas , Andreia S. Barros , Helena Almeida , José das Neves , Bruno Sarmento , Rute Nunes

{"title":"Oral delivery of tunable oxidation-responsive budesonide-loaded nanoparticles enhances inflammation modulation in intestinal colitis","authors":"Cecília Cristelo , Juliana Viegas , Andreia S. Barros , Helena Almeida , José das Neves , Bruno Sarmento , Rute Nunes","doi":"10.1016/j.jconrel.2025.113948","DOIUrl":"10.1016/j.jconrel.2025.113948","url":null,"abstract":"<div><div>The rising global prevalence and socio-economic impact of Inflammatory Bowel Disease (IBD) highlight the pressing demand of innovative solutions. Drug-targeting technologies are urgently needed to effectively deliver drugs directly to the affected areas of the gastrointestinal tract (GIT). In this work, a surface-tunable nanosystem responsive to reactive oxygen species (ROS) was developed for the focal oral delivery of budesonide to IBD affected GIT areas. Poly(lactic-<em>co</em>-glycolic) acid (PLGA) nanoparticles (NPs) were functionalized with a dense hydrophilic polyethylene glycol (PEG) corona linked by a ROS-sensitive moiety to obtain cleavable PEG (CleavPEG) NPs. CleavPEG NPs with nearly 100 nm and high association efficiency (∼70 %) presented an oxidation-responsive <em>in vitro</em> release of budesonide highly associated (> 60 %) with epithelial intestinal cells and macrophages without decreasing cell metabolic activity. In an inflamed 3D intestinal model, budesonide association to NPs allowed for minimal permeation of budesonide, when compared to its free form, with a similar reduction of IL-8, CXCL10/IP-10 and CCL20/MIP3a. Moreover, in a DSS-induced colitis mice model, CleavPEG NPs accumulated more in the colon than PEG NPs without cleavable linker, and repeated oral treatment with budesonide-loaded CleavPEG NPs decreased intestinal inflammation: confirmed by colonoscopy and quantified by a disease activity index (DAI) and levels of pro-inflammatory cytokines in colon comparable to healthy animals. CleavPEG NPs were efficiently responsive to oxidative environment, and improved budesonide efficacy in resolving inflammation, showing promise for the treatment of IBD.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113948"},"PeriodicalIF":10.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260400","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}

引用次数: 0

A thermoresponsive magnetic nanocarrier with the DNA-mimetic base pairing-guided controlled release of methotrexate in the treatment of rheumatoid arthritis 一种热响应性磁性纳米载体，具有dna模拟碱基配对引导的甲氨蝶呤控释治疗类风湿性关节炎

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-11 DOI: 10.1016/j.jconrel.2025.113952

Cheng Chen , Qingyun Wei , Zhen Zhu , Wenhui Wu , Tiantian Gong , Yangbo Lv , Aimei Zhang , Chunping Hu , Qichen Zhan , Tao Cao , Peng Cao

{"title":"A thermoresponsive magnetic nanocarrier with the DNA-mimetic base pairing-guided controlled release of methotrexate in the treatment of rheumatoid arthritis","authors":"Cheng Chen , Qingyun Wei , Zhen Zhu , Wenhui Wu , Tiantian Gong , Yangbo Lv , Aimei Zhang , Chunping Hu , Qichen Zhan , Tao Cao , Peng Cao","doi":"10.1016/j.jconrel.2025.113952","DOIUrl":"10.1016/j.jconrel.2025.113952","url":null,"abstract":"<div><div>Controlled drug delivery systems not only augment the therapeutic efficacy of drugs but also mitigate their adverse effects. Methotrexate (MTX) is a prominent first-line therapeutic agent in the management of rheumatoid arthritis (RA), yet it is characterized by its limited aqueous solubility, pronounced hemolytic activity, and propensity for off-target binding, which collectively contribute to its significant toxicity profile. To address these issues, a temperature-responsive controlled release system for MTX based on the analogous base pairing rule was designed for the RA treatment. Magnetic ferroferric oxide nanoparticles (Fe<sub>3</sub>O<sub>4</sub> NPs) coated with polydopamine (PDA) were modified with thymidine-1-acetic acid (TAA) to prepare nanocarrier (FPT NPs). Furthermore, the thymine molecules within the FPT NPs possessed the strong ability to specifically bind with the pteridine structure present in MTX, thereby enabling the fabrication of a nanomedicine (designated as FPT-MTX NPs) through the base pairing rule. Under the influence of an applied magnetic field, the FPT-MTX NPs demonstrated a remarkable capacity for precisely targeting the joint tissue in a mouse model of RA. Analogous to DNA, where double-strand breaks occurred due to heating-induced disruption of base pairing, MTX was released from FPT-MTX NPs following near-infrared irradiation-induced light-to-heat conversion. This mechanism facilitated the achievement of satisfactory therapeutic outcomes in the RA treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113952"},"PeriodicalIF":10.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260224","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}

引用次数: 0

A biodegradable suction patch for sustainable transbuccal peptide delivery 一种可生物降解的吸痰贴，用于可持续的经口腔肽输送

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-11 DOI: 10.1016/j.jconrel.2025.113947

Hanna Krupke , Nicole Zoratto , Lucie Rabut , Daniel Gao , Nevena Paunović , David Klein Cerrejon , Benoit Dehapiot , Jean-Christophe Leroux

{"title":"A biodegradable suction patch for sustainable transbuccal peptide delivery","authors":"Hanna Krupke , Nicole Zoratto , Lucie Rabut , Daniel Gao , Nevena Paunović , David Klein Cerrejon , Benoit Dehapiot , Jean-Christophe Leroux","doi":"10.1016/j.jconrel.2025.113947","DOIUrl":"10.1016/j.jconrel.2025.113947","url":null,"abstract":"<div><div>Despite considerable advances in the systemic delivery of peptides, their susceptibility to gastrointestinal degradation and high molecular weight, which restricts permeability across biological barriers, remain obstacles to oral administration. As a result, most peptide therapies rely on injections to achieve therapeutic effects. Recent studies on a bioinspired suction patch demonstrated positive effects <em>in vivo</em> with three peptides – desmopressin, semaglutide, and teriparatide – yet materials used for patch fabrication were non-degradable. In this work, a more sustainable patch alternative is introduced by replacing previously used materials with biodegradable polymers, aiming for degradation of the patch after removal to reduce environmental impact. A scalable mold casting process was employed to thermally crosslink synthesized and functionalized copolyesters, yielding the desired devices. Mechanical testing across various materials and shapes identified the best-performing polymer, while its degradation was confirmed in both aqueous medium and simulated waste. An <em>ex vivo</em> model using porcine buccal tissue validated the functionality of biodegradable patches, showing enhanced permeation of a poorly permeable dye when combined with a chemical permeation enhancer. In beagle dogs, the bioavailability of semaglutide (4.11 kDa) was substantially improved compared to the commercially available tablet, with an application time of only 10 min. Additionally, the patch achieved a relative bioavailability of 26% for bremelanotide (1.03 kDa) compared to subcutaneous administration. This work underscores the potential of replacing silicone devices with biodegradable alternatives, providing a more sustainable approach for peptide delivery <em>via</em> the buccal suction patch.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113947"},"PeriodicalIF":10.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260219","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}

引用次数: 0

Polypeptide-protein conjugation: A new paradigm for therapeutic protein delivery 多肽-蛋白偶联：治疗性蛋白递送的新范式

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-11 DOI: 10.1016/j.jconrel.2025.113953

Xiao Zhang , Shiwei Fu , Bowen Zhao , Yilin Liu , Ronald S. Seruya , Fuwu Zhang

{"title":"Polypeptide-protein conjugation: A new paradigm for therapeutic protein delivery","authors":"Xiao Zhang , Shiwei Fu , Bowen Zhao , Yilin Liu , Ronald S. Seruya , Fuwu Zhang","doi":"10.1016/j.jconrel.2025.113953","DOIUrl":"10.1016/j.jconrel.2025.113953","url":null,"abstract":"<div><div>Protein therapeutics have emerged as a potent and highly targeted treatment for a wide range of diseases, including cancer, immune disorders, and genetic conditions. However, their clinical applications are often constrained by challenges such as low stability, short circulation half-life, immunogenic responses, and high manufacturing expenses. The rapid development of biodegradable and biocompatible polypeptide materials provides innovative strategies to address these limitations. In particular, polypeptide-protein conjugation, the covalent linkage of a polypeptide chain to therapeutic proteins, has emerged as a promising strategy for enhancing specific delivery of therapeutic proteins. Leveraging the unique properties of polypeptides, these conjugates significantly improve the stability, solubility, and bioavailability of therapeutic proteins, thereby enhancing their therapeutic efficacy and reducing side effects. This review comprehensively summarizes the recent progress in this field, discussing the current obstacles faced by therapeutic proteins in clinical applications, fundamental design principles, and methodologies for constructing well-defined polypeptide-protein conjugates. Key advancements discussed include innovations in polypeptide synthesis, protein modification, bioorthogonal reactions for precise conjugation, techniques for conjugate purification and characterization. The review further summarizes recent progresses of various polypeptide-protein conjugates for therapeutic protein delivery. Current obstacles and future research directions are also highlighted, underscoring the potential of polypeptide-protein conjugation to propel further advancement in therapeutic protein delivery.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113953"},"PeriodicalIF":10.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269251","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}

引用次数: 0

Advanced biomaterials for the targeted delivery of immune checkpoint inhibitors to solid tumors 针对实体肿瘤靶向递送免疫检查点抑制剂的先进生物材料

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-11 DOI: 10.1016/j.jconrel.2025.113951

Emily M. Henrich , Kevin J. McHugh

{"title":"Advanced biomaterials for the targeted delivery of immune checkpoint inhibitors to solid tumors","authors":"Emily M. Henrich , Kevin J. McHugh","doi":"10.1016/j.jconrel.2025.113951","DOIUrl":"10.1016/j.jconrel.2025.113951","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized the way cancer is treated by engaging the patient's own immune system to attack cancer. ICIs can also achieve favorable outcomes in patients whose cancers are unresponsive or resistant to first-line therapies. Despite these exciting prospects, ICIs are ineffective in many patients and cause immune-related adverse events (irAEs) in up to 89 % of patients. Therefore, there is a clear clinical need to reduce irAEs while maintaining or improving the therapeutic efficacy of ICIs. The local administration of ICIs through intratumoral injection or peritumoral administration has been shown to increase the potency of these therapeutics while reducing irAEs and extending survival in preclinical models. However, the rapid systemic distribution of intratumorally delivered drugs (hours) prevents this strategy from achieving even better efficacy and reduced toxicity; this is particularly problematic for ICIs due to their long biological (weeks), consequently acting at non-target sites for weeks before being cleared by the body. Engineered biomaterials have the potential to enhance local administration by improving permeation and retention, employing antibody-mediated targeting, leveraging tumor microenvironment sense-and-respond systems, or taking advantage of cell trafficking. This paper reviews the cutting-edge delivery strategies shown to improve the safety and efficacy of drugs targeting PD-1, PD-L1, and CTLA-4 and identifies the most promising strategies for clinical translation.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113951"},"PeriodicalIF":10.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260220","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}

引用次数: 0

Novel biomarker discovery-coupled plasma therapy with enhanced tumor penetration for non-surgical treatment of cervical cancer 新的生物标志物发现-结合血浆治疗与增强肿瘤穿透非手术治疗宫颈癌

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-06-10 DOI: 10.1016/j.jconrel.2025.113946

Sung Wook Kim , Min-Jung Kang , Youngsun Kim , Woo Yeon Hwang , Aram Lee , Quoc-Viet Le , Ihn Han , Min Hyung Jung , Kiyong Na , Kyung Sook Kim , Sung Jong Lee , Dong Soo Suh , Ki Hyung Kim , Kyung Un Choi , Eun Ha Choi , Gayong Shim , Jongmin Kim , Byung Su Kwon

{"title":"Novel biomarker discovery-coupled plasma therapy with enhanced tumor penetration for non-surgical treatment of cervical cancer","authors":"Sung Wook Kim , Min-Jung Kang , Youngsun Kim , Woo Yeon Hwang , Aram Lee , Quoc-Viet Le , Ihn Han , Min Hyung Jung , Kiyong Na , Kyung Sook Kim , Sung Jong Lee , Dong Soo Suh , Ki Hyung Kim , Kyung Un Choi , Eun Ha Choi , Gayong Shim , Jongmin Kim , Byung Su Kwon","doi":"10.1016/j.jconrel.2025.113946","DOIUrl":"10.1016/j.jconrel.2025.113946","url":null,"abstract":"<div><div>There is a growing need for non-surgical, fertility-preserving treatments for young patients with cervical cancer. This study explores biomarker-driven non-thermal plasma (NTP) therapy as a localized therapeutic strategy with deep tissue penetration, highlighting its potential for controlled oxidative modulation and targeted drug delivery. Screening of ROS-related molecules revealed an association between sensitivity to NTP and the expression of the antioxidant enzyme superoxide dismutase 1 (SOD1), with human papillomavirus (HPV) oncoprotein E6 and p53 identified as upstream regulators. Additionally, NTP was shown to influence toll-like receptor signaling 9 and induce immunogenic cell death (ICD), enhancing localized immune activation within the tumor microenvironment. In a xenografted animal tumor model, SOD1 was identified as a potential biomarker for NTP, while in a syngeneic tumor model using TC-1 cell lines expressing HPV16-E6 and HPV16-E7, NTP treatment demonstrated both antitumor effects and an increase in tumor-infiltrating lymphocytes. Evaluation of NTP penetration in patient uterine tissues showed that the depth of penetration was significantly greater in the transformation zone, where cervical cancer occurs, than in the squamous zone. Notably, NTP reached a penetration depth of ∼5 mm in cervical cancer tissues, suggesting its potential as a drug delivery enhancer for localized therapeutic applications. These findings suggest that NTP may serve as a novel non-invasive platform for controlled therapeutic delivery in cervical cancer treatment, offering an alternative to conventional surgical approaches.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"384 ","pages":"Article 113946"},"PeriodicalIF":10.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260222","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}

引用次数: 0