Journal of Controlled Release最新文献_第3页

Manganese oxide nanoparticle acts as a promising immune adjuvant via tuning ferroptosis signaling 氧化锰纳米颗粒通过调控铁凋亡信号作为一种有前景的免疫佐剂

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-07-09 DOI: 10.1016/j.jconrel.2025.114022

Xiaoyu Liang, Shanshan Qi, Lirong Fang, Yue Wu, Canquan Mao, Yuhong Jiang

{"title":"Manganese oxide nanoparticle acts as a promising immune adjuvant via tuning ferroptosis signaling","authors":"Xiaoyu Liang, Shanshan Qi, Lirong Fang, Yue Wu, Canquan Mao, Yuhong Jiang","doi":"10.1016/j.jconrel.2025.114022","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114022","url":null,"abstract":"While aluminum is one of the most commonly-used adjuvants in vaccine strategies, there are emerging explorations on other metals, which can trigger excellent immunoenhancing effects. Manganese (Mn) as an essential trace metal has been considered to amplify immune responses, however, it is still needed for probing the detailed adjuvant mechanism and functions. This work constructed manganese oxide nanoparticles (Mn NPs) to deliver antigens and revealed that Mn NPs, but not Mn<sup>2+</sup> or aluminum, largely promoted antigen uptake, DC maturation, CD4<sup>+</sup>/CD8<sup>+</sup> T cell responses and humoral immune responses, suggesting that nanoparticle form augmented the adjuvanticity of Mn<sup>2+</sup>. Moreover, these effects were dose-dependent since H<img alt=\"single bond\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/sbnd.gif\" style=\"vertical-align:middle\"/>Mn NP with high dosage exerted more remarkable immunoenhancements than L-Mn NP and M-Mn NP. Significantly, it uncovered the adjuvant mechanism involving immune cell death signaling, in which H<img alt=\"single bond\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/sbnd.gif\" style=\"vertical-align:middle\"/>Mn NP mitigated the ferroptosis of immune cells to elevate immune responses via crosstalk with STING/NLRP3 signaling. Intriguingly, H<img alt=\"single bond\" src=\"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/55/entities/sbnd.gif\" style=\"vertical-align:middle\"/>Mn NP triggered adverse effects in ferroptosis, which stimulated ferroptosis in cancer cells to attenuate tumor progression, indicating that the role of Mn NPs in ferroptosis depended on cell types and context. Therefore, it highlighted that manganese nanoparticles possessed extraordinary adjuvant capacity for vaccine efficacy and anti-tumor immunotherapy mainly through ferroptosis signaling.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"72 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586831","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

Recent advances and challenges of injectable hydrogels in drug delivery 注射水凝胶在给药中的最新进展和挑战

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-09 DOI: 10.1016/j.jconrel.2025.114021

Anna Guo , Qiannan Cao , Huapan Fang , Huayu Tian

{"title":"Recent advances and challenges of injectable hydrogels in drug delivery","authors":"Anna Guo , Qiannan Cao , Huapan Fang , Huayu Tian","doi":"10.1016/j.jconrel.2025.114021","DOIUrl":"10.1016/j.jconrel.2025.114021","url":null,"abstract":"<div><div>Injectable hydrogels, serving as multifunctional biomaterials, exhibit exceptional shear-thinning behavior, tunable mechanical properties, and biocompatibility, attributed to their dynamic porous network structure and biomimetic microenvironment characteristics. It can be used as a drug carrier to achieve precise delivery and controlled release, and regulate cell behavior through biomimetic microenvironment, which has important application prospects in minimally invasive therapy and regenerative medicine. This review systematically describes their classifications, preparation methods, functional modifications, performance optimization and the latest advances including drug and cell delivery, and tissue engineering. Moreover, the current challenges associated with their clinical translation are also discussed, along with strategies to overcome these hurdles. Finally, the future research directions of injectable hydrogels are outlined, with an emphasis on enhancing their clinical applicability and overcoming current technological and clinical barriers to promote the widespread use in precision medicine and personalized therapies. This work will provide valuable insights for the design and application of injectable hydrogel-based biomaterials in biomedicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114021"},"PeriodicalIF":10.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586837","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

Formulation methods for peptide-modified lipid nanoparticles 肽修饰脂质纳米颗粒的制备方法

IF 10.8 1区医学

Journal of Controlled Release Pub Date : 2025-07-09 DOI: 10.1016/j.jconrel.2025.114030

Katelyn Miyasaki, Sangwoo Han, Olivia Carton, Rebecca M. Kandell, Jonathan Gunn, Ester J. Kwon

{"title":"Formulation methods for peptide-modified lipid nanoparticles","authors":"Katelyn Miyasaki, Sangwoo Han, Olivia Carton, Rebecca M. Kandell, Jonathan Gunn, Ester J. Kwon","doi":"10.1016/j.jconrel.2025.114030","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.114030","url":null,"abstract":"Lipid nanoparticles (LNPs) are a promising non-viral gene carrier, but one significant unmet challenge is cell-specific delivery in extrahepatic organs. Peptides are one class of targeting ligand that have been used to target nanoparticles, including LNPs. Herein, we compared two formulation approaches that use the polyethylene glycol (PEG)-lipid to display targeting peptides: (1) post-conjugation targeted (PCT), in which LNPs were formulated with PEG-lipid with chemical handles and subsequently modified with peptides, and (2) in-line targeted (ILT), in which peptide-PEG-lipid conjugates were directly used in LNP formulation<em>.</em> We observed that PCT and ILT LNPs had similar physicochemical properties, but ILT LNPs aggregated when formulated with a large peptide. Using cyclic RGD as a model ligand, we observed that while binding and uptake of LNPs in cultured cells were similar between approaches, PCT LNPs led to higher activity. Systemic administration revealed that LNPs formulated with both methods led to shifts in organ biodistribution compared to untargeted LNPs, but PCT resulted in higher transfection compared to ILT. Finally, analysis of cell tropism showed that the transfection activity of cRGD LNPs was shifted towards endothelial cells in multiple organs. We conclude that while PCT LNPs required more processing steps over the ILT LNPs, they led to superior formulations that led to active peptide targeting.","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"14 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586832","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

Lecithin-modified hybrid nanocarriers for enhanced locoregional therapy of melanoma: Influence of surface modification on therapeutic response 用于增强黑色素瘤局部治疗的卵磷脂修饰杂交纳米载体：表面修饰对治疗反应的影响

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-08 DOI: 10.1016/j.jconrel.2025.114020

Alexander S. Timin , Vladislava A. Rusakova , Kseniia E. Ilina , Anna Rogova , Yulia A. Tishchenko , Darya R. Akhmetova , Irina A. Gorbunova , Daria A. Shipilovskikh , Dmitriy V. Lipin , Sergei A. Shipilovskikh

{"title":"Lecithin-modified hybrid nanocarriers for enhanced locoregional therapy of melanoma: Influence of surface modification on therapeutic response","authors":"Alexander S. Timin , Vladislava A. Rusakova , Kseniia E. Ilina , Anna Rogova , Yulia A. Tishchenko , Darya R. Akhmetova , Irina A. Gorbunova , Daria A. Shipilovskikh , Dmitriy V. Lipin , Sergei A. Shipilovskikh","doi":"10.1016/j.jconrel.2025.114020","DOIUrl":"10.1016/j.jconrel.2025.114020","url":null,"abstract":"<div><div>Nanomedicine has enormous potential and can overcome the limitations of conventional methods of cancer therapy. However, a major problem is still unfavorable tumor biodistribution of nanocarriers that can lead to inefficient cancer therapy. The surface modification of nanoparticles (NPs) can increase the depth of tumor penetration and improve therapeutic outcome. This study demonstrates the enhanced therapeutic effect of lecithin-modified silica NPs (LSi NPs, < 100 nm in size, D<sub>h</sub> ∼ 150–190 nm) loaded with anticancer drug (ATS) for locoregional therapy of melanoma. Both <em>in vitro</em> and <em>in vivo</em> investigations confirmed that the lecithin functionalization not only leads to uniform intratumoral biodistribution of NPs, but also provides a more pronounced therapeutic effect on melanoma. In particular, fluorescent imaging showed increased cellular uptake and tumor spheroid penetration (B16-F10, 4T1 and CT26 cells) in case of LSi NPs. By employing localized injection of the developed NPs, their biodistribution in the tumors was determined to be 96.35–98.84 %ID/g. The evaluation of <em>in vivo</em> antitumor efficiency revealed a significant reduction of the tumor growth for lecithin-modified nanocarriers (ATS@LSi NPs) compared to non-modified nanocarriers (ATS@Si NPs): ∼ 0.25 cm<sup>3</sup> <em>versus</em> ∼ 1.1 cm<sup>3</sup>). No unwanted side effects were observed during the therapy, as confirmed by body weight measurements and histological analysis of key organs, including the heart, lungs, liver, spleen, and kidneys. Thus, we believe this study will aid in the design of nanocarriers for cancer therapy and help to accelerate the clinical translation of nanomedicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114020"},"PeriodicalIF":10.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578255","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

The impact of peptide surface density on PD-L1 receptor inhibition as a therapeutic strategy for triple negative breast cancer 肽表面密度对PD-L1受体抑制的影响作为三阴性乳腺癌的治疗策略

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-07 DOI: 10.1016/j.jconrel.2025.114019

Naira Keshishian, Rudolf G. Abdelmessih, Debra T. Auguste

{"title":"The impact of peptide surface density on PD-L1 receptor inhibition as a therapeutic strategy for triple negative breast cancer","authors":"Naira Keshishian, Rudolf G. Abdelmessih, Debra T. Auguste","doi":"10.1016/j.jconrel.2025.114019","DOIUrl":"10.1016/j.jconrel.2025.114019","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) disrupt receptor signaling, allowing the immune system to recognize and eliminate tumor cells across various cancers. ICI therapies have success in some cancers; however, most cancer patients do not show a therapeutic response. Antibodies, the current standard for ICIs, exhibit limited tumor penetration and immune-related side effects prompting the need for alternative strategies. Peptides are a promising alternative with the potential to overcome these limitations; however, their moderate binding affinity necessitates delivery platforms that enhance their therapeutic potential. Coupling peptides to nanoscale drug delivery systems such as liposomes has enhanced peptide binding affinity, selectivity and in vivo effectiveness. In this study, programmed cell death ligand 1 (PD-L1) antagonist peptides were conjugated to liposomes at varying surface densities to investigate the impact of density on tumor progression and immune cell infiltration. In vitro studies revealed that increasing the peptide density from 9000 peptides/μm<sup>2</sup> (1 mol%) to 53,000 peptides/μm<sup>2</sup> (3 mol%) enhanced binding extent, affinity, and rate. In contrast, in vivo studies showed that higher-density formulations had reduced tumor accumulation and no therapeutic effect, while the 24,000 peptides/μm<sup>2</sup> (1.5 mol%) formulation significantly inhibited tumor growth and promoted CD8<sup>+</sup> T cell infiltration. These findings highlight the importance of optimizing ligand density for effective peptide-based ICI therapies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114019"},"PeriodicalIF":10.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568757","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

Nanomodulation of blood-labyrinth barrier enhances neuroprotection and antioxidant intervention for noise-induced hearing loss 血液迷宫屏障的纳米调节增强了噪声性听力损失的神经保护和抗氧化干预

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-07 DOI: 10.1016/j.jconrel.2025.114006

Ke Xu , Wenjing Li , Qingjun Jiang , Dehong Yu , Yu Chen , Xueling Wang

{"title":"Nanomodulation of blood-labyrinth barrier enhances neuroprotection and antioxidant intervention for noise-induced hearing loss","authors":"Ke Xu , Wenjing Li , Qingjun Jiang , Dehong Yu , Yu Chen , Xueling Wang","doi":"10.1016/j.jconrel.2025.114006","DOIUrl":"10.1016/j.jconrel.2025.114006","url":null,"abstract":"<div><div>The treatment of noise-induced hearing loss (NIHL) is challenged by the blood-labyrinth barrier (BLB), which impedes effective drug delivery to the cochlea. NIHL serves as a model for sensorineural hearing loss (SNHL), highlighting the urgent need for advanced therapeutic strategies that can traverse BLB and target cochlear pathology. Here, we report the development of tFNA-RA@G-Ang2, a multi-stage, biomimetic nanocomposite designed for targeted inner ear therapy. This platform integrates tetrahedral framework nucleic acids (tFNA) to enhance cellular internalization, gelatin nanoparticles (GNPs) with MMP2-responsive degradability for dynamic size modulation, and Ang2 peptide functionalization for low-density lipoprotein receptor-related protein 1 (LRP1)-mediated transcytosis across the BLB. These features enable efficient delivery of rosmarinic acid (RA) to cochlear synapses and neurons, maximizing neuroprotection and antioxidant effects. The enzymatic degradation of GNPs enables controlled nanoparticle disassembly, facilitating deep cochlear penetration and prolonged retention. In vitro and in vivo studies demonstrate that tFNA-RA@G-Ang2 significantly reduces oxidative stress, protects cochlear ribbon synapses, prevents neuronal apoptosis, and restores auditory function in NIHL treatment. This approach outperforms conventional delivery systems by integrating biomimetic targeting, enzymatic-triggered adaptability, and spatiotemporal control. Collectively, our work offers a versatile platform for overcoming BLB-related therapeutic barriers, with broad implications for NIHL, age-related hearing loss, ototoxicity, and inner ear neuroprotection.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114006"},"PeriodicalIF":10.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568680","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

Irinotecan and dexamethasone prodrug co-loaded liposomes for the treatment of breast cancer 伊立替康和地塞米松前药共载脂质体治疗乳腺癌

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-07 DOI: 10.1016/j.jconrel.2025.114017

Mei Chen , Hongbing Liu , Mengqi Xiu , Muse Ji , Dongmei Shi , Jingxin Gou , Haibing He , Tian Yin , Xing Tang , Guoliang Chen , Yu Zhang

{"title":"Irinotecan and dexamethasone prodrug co-loaded liposomes for the treatment of breast cancer","authors":"Mei Chen , Hongbing Liu , Mengqi Xiu , Muse Ji , Dongmei Shi , Jingxin Gou , Haibing He , Tian Yin , Xing Tang , Guoliang Chen , Yu Zhang","doi":"10.1016/j.jconrel.2025.114017","DOIUrl":"10.1016/j.jconrel.2025.114017","url":null,"abstract":"<div><div>Cancer is a major global health challenge, which has a serious impact on human health and life. While Irinotecan (IRI) has been demonstrated to treat various cancers with remarkable efficacy, addressing its associated side effects remains a critical concern in clinical. Chemotherapy drugs are often used in combination with dexamethasone (DEX) in clinical practice to reduce their side effects. Besides, DEX can enhance the anti-tumor effect by improving tumor microenvironment (TME) and anti-inflammation. Therefore, in this study, IRI and DPD (DEX prodrug) co-loaded liposomes (LipID) were constructed to improve the side effects and anti-tumor efficacy. It was found that LipID had an average size of 108.60 ± 0.36 nm with a narrow PDI of 0.098 ± 0.020. The encapsulation efficiency (EE) of either IRI or DPD was further determined to be more than 95 %. Furthermore, the results of <em>in vitro</em> release indicated that LipID exhibited sequential release characteristics. Cells and animal experiments clarified that preferential release of DPD contributed to improving TME and facilitate greater accumulation of drugs within the tumors. Besides, the combined application of IRI and DPD could also reduce the side effects caused by IRI, achieving the goal of enhancing efficacy while minimizing toxicity. Therefore, LipID has excellent prospects for efficient tumor inhibition and clinical application.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114017"},"PeriodicalIF":10.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568758","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

Low-frequency ultrasound-mediated blood-brain barrier opening enables non-invasive lipid nanoparticle RNA delivery to glioblastoma 低频超声介导的血脑屏障打开使非侵入性脂质纳米颗粒RNA递送到胶质母细胞瘤

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-07 DOI: 10.1016/j.jconrel.2025.114018

Maya Shumer-Elbaz , Nitay Ad-El , Yulia Chulanova , Dor Brier , Meir Goldsmith , Mike Bismuth , Alina Brosque , Roni Gattegno , Divsha Sher , Anna Gutkin , Dana Bar-On , Dinorah Friedmann-Morvinski , Dan Peer , Tali Ilovitsh

{"title":"Low-frequency ultrasound-mediated blood-brain barrier opening enables non-invasive lipid nanoparticle RNA delivery to glioblastoma","authors":"Maya Shumer-Elbaz , Nitay Ad-El , Yulia Chulanova , Dor Brier , Meir Goldsmith , Mike Bismuth , Alina Brosque , Roni Gattegno , Divsha Sher , Anna Gutkin , Dana Bar-On , Dinorah Friedmann-Morvinski , Dan Peer , Tali Ilovitsh","doi":"10.1016/j.jconrel.2025.114018","DOIUrl":"10.1016/j.jconrel.2025.114018","url":null,"abstract":"<div><div>Ionizable Lipid Nanoparticles (LNP) are an FDA-approved non-viral RNA delivery system, though their use for brain therapy is restricted by the blood-brain barrier (BBB). Focused ultrasound combined with microbubbles can disrupt the BBB, but delivering large particles requires balancing increased peak negative pressures while maintaining microvascular integrity. Herein, we optimized low-frequency focused ultrasound (FUS) parameters to induce high-amplitude microbubble oscillations, enabling the safe delivery of LNPs across the BBB. First, BBB opening was assessed at different frequencies (850, 250, and 80 kHz) and pressures by monitoring the extravasation of Evans blue (∼1 kDa). Next, the delivery of 4, 70, and 150 kDa Dextrans, LNPs entrapping Cy5-siRNAs (∼70 nm in diameter), and LNPs entrapping mRNA (∼100 nm in diameter) was evaluated via microscopy and bioluminescence. Two types of LNPs containing different ionizable lipids (SM-102 and Lipid-14) were compared and both achieved successful brain delivery following FUS-mediated BBB opening. In a glioblastoma syngeneic mouse model, where the BBB remains largely intact under baseline conditions, siRNA-Cy5-LNP was successfully delivered. A frequency of 850 kHz and 180 kPa pressure induced safe BBB opening, enabling delivery of both small molecules and LNPs. In healthy brains, LNP entrapping siRNAs delivery increased 10-fold compared to controls, and LNPs with mRNAs showed a 12-fold increase in bioluminescence after 24 h. In glioblastoma tumors, LNPs with siRNAs delivery resulted in a 6.7-fold increase in fluorescence. This study paves the way for non-invasive LNP delivery to the brain, offering a versatile platform for brain therapies.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114018"},"PeriodicalIF":10.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568756","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 delayed-melting cryomicroneedle system for probiotic delivery against invasive Candida albicans infection 一种用于抗侵袭性白色念珠菌感染的益生菌输送的延迟融化低温微针系统

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-06 DOI: 10.1016/j.jconrel.2025.114016

Qin Yu , Zhichao Chang , Yuhan Sun , Fenfen Ma , Haisheng He , Yi Lu , Zongguang Tai , Quangang Zhu , Jingyuan Wen , Zhongjian Chen , Wei Wu

{"title":"A delayed-melting cryomicroneedle system for probiotic delivery against invasive Candida albicans infection","authors":"Qin Yu , Zhichao Chang , Yuhan Sun , Fenfen Ma , Haisheng He , Yi Lu , Zongguang Tai , Quangang Zhu , Jingyuan Wen , Zhongjian Chen , Wei Wu","doi":"10.1016/j.jconrel.2025.114016","DOIUrl":"10.1016/j.jconrel.2025.114016","url":null,"abstract":"<div><div>The resilience of <em>Candida albicans</em> (<em>C. albicans</em>) biofilms against conventional antifungals necessitates innovative therapeutic strategies. This study presents a delayed-melting cryomicroneedle (cryoMN) platform that enables dermal delivery of <em>Lacticaseibacillus rhamnosus</em> LA3, a probiotic strain exhibiting superior anti<em>-C. albicans</em> activity among the five screened candidates. LA3 achieved a 1.01-lg reduction in planktonic <em>C. albicans</em> viability within 48 h of co-culture while maintaining self-proliferation. Its cell-free supernatant (CFS) displayed concentration-dependent antifungal efficacy, with 50 % CFS resulting in 62.6 % inhibition of planktonic <em>C. albicans</em> and 98 % reduction in biofilm biomass, as confirmed by confocal laser scanning microscopy, which revealed structural biofilm collapse. In infected keratinocyte models, LA3 restored cell viability to approximately 90 % (compared with ≤79.3 % in controls). A biofilm-mimicking gelatin-hyaluronic acid hydrogel scaffold was developed, preserving >90 % probiotic viability for 5 days at 4 °C, relaxing frozen-chain requirement while maintaining microneedle integrity. In murine models of invasive <em>candidiasis</em>, LA3-loaded cryoMNs demonstrated superior therapeutic efficacy compared with both topical LA3 gel and clotrimazole cream, with excellent biosafety (> 90 % cell viability, < 5 % hemolysis, and no detectable organ toxicity). By integrating strain-optimized probiotics with biomimetic delivery technology, this platform represents a minimally invasive strategy for treating deep-seated fungal infections.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114016"},"PeriodicalIF":10.5,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568761","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

Microenvironment responsive nanoplatform for targeted removal of cholesterol and reshaping inflammatory microenvironment in atherosclerotic plaques 微环境响应纳米平台用于靶向去除胆固醇和重塑动脉粥样硬化斑块中的炎症微环境

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-07-06 DOI: 10.1016/j.jconrel.2025.114000

Lin Shen , Chengli Jiang , Jingjing Song , Yanran Bi , Weiqian Chen , Chenying Lu , Minjiang Chen , Lingchun Lv , Risheng Yu , Jianhua Zou , Zhongwei Zhao , Xiaoyuan Chen , Jiansong Ji

{"title":"Microenvironment responsive nanoplatform for targeted removal of cholesterol and reshaping inflammatory microenvironment in atherosclerotic plaques","authors":"Lin Shen , Chengli Jiang , Jingjing Song , Yanran Bi , Weiqian Chen , Chenying Lu , Minjiang Chen , Lingchun Lv , Risheng Yu , Jianhua Zou , Zhongwei Zhao , Xiaoyuan Chen , Jiansong Ji","doi":"10.1016/j.jconrel.2025.114000","DOIUrl":"10.1016/j.jconrel.2025.114000","url":null,"abstract":"<div><div>The microenvironment of atherosclerotic plaques features abundant cholesterol crystals (CCs), reactive oxygen species (ROS), and pro-inflammatory M1 macrophages, leading to the progression and mortality of atherosclerotic cardiovascular disease (ASCVD). Targeted removal of CCs and scavenging of ROS are crucial for treatment of ASCVD. In this study, an intelligent nanoformulation consisting of epigallocatechin gallate (EGCG), cysteine (Cys), ursodeoxycholic acid (UDCA) and VHPK (Valine-Histidine-Proline-Lysine)-Lipo, was designed to precisely target and remodel the inflammatory microenvironment of atherosclerotic plaques. With the assistance of VHPK peptide-modified liposomes, this nanoplatform significantly enhances the targeting ability and therapeutic efficacy. UDCA promotes cholesterol dissolution and efflux and improves cholesterol clearance in foam cells by over 70 %. EGCG, an antioxidant, significantly enhances ROS clearance by approximately 50 %. EGCG/Cys/UDCA@VHPK-Lipo boosts plaque clearance efficiency by 75.43 % <em>in vivo</em>. RNA-seq analysis reveals that these nanoparticles upregulate ATP-binding cassette transporters A1 (<em>ABCA1</em>) and G1 (<em>ABCG1</em>) expression, promoting cholesterol metabolism and M2 macrophage polarization. Additionally, inflammation markers in plasma and plaque tissues were significantly reduced, indicating good biocompatibility and safety. EGCG/Cys/UDCA@VHPK-Lipo demonstrates superior plaque clearance and safety both <em>in vitro</em> and <em>in vivo</em>, offering promising clinical potential for atherosclerosis treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"385 ","pages":"Article 114000"},"PeriodicalIF":10.5,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565820","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}

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