Journal of Controlled Release最新文献_第2页

Polyphenol-based pH-responsive nanoparticles enhance chemo-immunotherapy in pancreatic cancer

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-16 DOI: 10.1016/j.jconrel.2025.02.021

Jieru Li , Yiwei Dai , Tao Wang , Xinyu Zhang , Pengcheng Du , Yuman Dong , Zuoyi Jiao

{"title":"Polyphenol-based pH-responsive nanoparticles enhance chemo-immunotherapy in pancreatic cancer","authors":"Jieru Li , Yiwei Dai , Tao Wang , Xinyu Zhang , Pengcheng Du , Yuman Dong , Zuoyi Jiao","doi":"10.1016/j.jconrel.2025.02.021","DOIUrl":"10.1016/j.jconrel.2025.02.021","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat due to its difficulty in early diagnosis, highly invasive nature, and high metastatic potential. Currently, the primary treatments for PDAC are chemotherapy and immunotherapy. However, the abundance of extracellular matrix and immunosuppressive cells in the tumor microenvironment (TME) severely impedes the effectiveness of chemotherapy and immunotherapy, promoting tumor growth and metastasis. Indoleamine 2,3-dioxygenase 1 (IDO1), an immunosuppressive tryptophan-metabolizing enzyme, is upregulated in PDAC and degrades tryptophan (Trp) into kynurenine (Kyn), which is toxic to effector T cells and induces regulatory T cells (Treg) recruitment. Herein, we propose a concise strategy to construct a biocompatible, polyphenol-based, pH-responsive nanoparticle to co-deliver docetaxel (DTX) and NLG919 (an IDO1 inhibitor) to significantly enhance chemo-immunotherapy for PDAC by remodeling the TME. The DTX/NLG919-loaded nanoparticles (FPND) effectively elicited immunogenic cell death (ICD) in PDAC cells while limiting immunosuppressive Kyn production through IDO1 inhibition. FPND triggered an effective anti-tumor immune response, characterized by increased CD8<sup>+</sup> T cells infiltration and decreased Treg recruitment, leading to significant inhibition of subcutaneous tumor growth in KPC mice through a combination of chemotherapy and immunotherapy. Overall, FPND nanoparticles showed excellent anti-tumor efficacy as a PDAC therapeutic strategy with broad potential in precision medicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 615-629"},"PeriodicalIF":10.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414362","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

Injectable hydrogel microspheres promoting inflammation modulation and nucleus pulposus-like differentiation for intervertebral disc regeneration

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-15 DOI: 10.1016/j.jconrel.2025.02.016

Yuhang Chen , Zhuo-Ran Yang , Zhangrong Cheng , Pengzhi Shi , Anran Zhang , Jing-Wen Fan , Zhiguo Zhao , Hao Jiang , Jintao Zhu , Yukun Zhang

{"title":"Injectable hydrogel microspheres promoting inflammation modulation and nucleus pulposus-like differentiation for intervertebral disc regeneration","authors":"Yuhang Chen , Zhuo-Ran Yang , Zhangrong Cheng , Pengzhi Shi , Anran Zhang , Jing-Wen Fan , Zhiguo Zhao , Hao Jiang , Jintao Zhu , Yukun Zhang","doi":"10.1016/j.jconrel.2025.02.016","DOIUrl":"10.1016/j.jconrel.2025.02.016","url":null,"abstract":"<div><div>Local inflammation modulation and stem cell therapy have attracted much attention in the treatment of intervertebral disc degeneration (IDD). However, severe oxidative stress and limited nucleus pulposus (NP)-like differentiation of stem cells largely impair biomaterial implantation's therapeutic efficacy. Due to their excellent performance in injectability and flowability, and minor compression to NP tissue, hydrogel microspheres have become an attractive carrier for IDD treatment. Herein, an injectable hydrogel microsphere consisting of Wnt5a-mimetic peptide Foxy5- and the antioxidative peptide-grafted gelatin methacryloyl matrix (GFA), was developed as a stem cell delivery system for IDD therapy. Being fabricated and encapsulating bone marrow-derived mesenchymal stem cells (BMSCs) using the microfluidic technology, GFA hydrogel microspheres ameliorate IDD by promoting inflammation inhibition, NP-like differentiation and extracellular matrix regeneration. They efficiently eliminated reactive oxygen species, and downregulated the inflammation level through the inhibition of interleukin-17B/nuclear factor-κB signaling pathway. Moreover, the NP-like differentiation of BMSCs was effectively stimulated by Foxy5 <em>via</em> the calcium/calmodulin dependent protein kinase kinase 2/protein kinase A/sex determining region Y box protein 9 signaling pathway, thereby leading to a rebalance between the generation and degradation of NP matrix. <em>In vivo</em> rat IDD model demonstrated that BMSC-loaded GFA hydrogel microspheres mitigated local inflammation, preserved disc height, and promoted intervertebral disc regeneration. In conclusion, this study introduces an BMSC-loaded injectable hydrogel microspheres as a promising therapy for regulating the microenvironment and alleviating the progression of IDD.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 599-614"},"PeriodicalIF":10.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408097","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

Inside back cover: Wanting Dai et al

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/S0168-3659(25)00124-5

引用次数: 0

Outside Back Cover: Anqi Ye et al

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/S0168-3659(25)00125-7

引用次数: 0

Multidrug micelles and sonopermeation for chemotherapy co-delivery to brain tumors.

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/j.jconrel.2025.02.018

Anshuman Dasgupta, Jan-Niklas May, Geir Klinkenberg, Helena C Besse, Eva Miriam Buhl, Diana Moeckel, Rahaf Mihyar, Quim Peña, Armin Azadkhah Shalmani, Christopher Hark, Anne Rix, Susanne Koletnik, Josbert Metselaar, Yang Shi, Wim E Hennink, Gert Storm, Dannis van Vuurden, Chrit Moonen, Mario Ries, Ruth Schmid, Fabian Kiessling, Twan Lammers

{"title":"Multidrug micelles and sonopermeation for chemotherapy co-delivery to brain tumors.","authors":"Anshuman Dasgupta, Jan-Niklas May, Geir Klinkenberg, Helena C Besse, Eva Miriam Buhl, Diana Moeckel, Rahaf Mihyar, Quim Peña, Armin Azadkhah Shalmani, Christopher Hark, Anne Rix, Susanne Koletnik, Josbert Metselaar, Yang Shi, Wim E Hennink, Gert Storm, Dannis van Vuurden, Chrit Moonen, Mario Ries, Ruth Schmid, Fabian Kiessling, Twan Lammers","doi":"10.1016/j.jconrel.2025.02.018","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.02.018","url":null,"abstract":"<p><p>Brain tumors are difficult to target and treat. The blood-brain barrier (BBB) limits drug delivery to pathological sites, and standard mono-chemotherapy typically results in suboptimal efficacy and development of drug resistance. We here set out to load a synergistic drug combination in polymeric micelles, and combined them with ultrasound- and microbubble-mediated BBB opening in glioma models in mice. Via high-throughput screening of various chemotherapy combinations in different glioma cell lines, valrubicin and panobinostat were identified as a synergic drug combination and co-loaded in mPEG-b-p(HPMAm-Bz)-based polymeric micelles. Intravenous administration of double-drug micelles showed good tolerability and resulted in significant tumor growth inhibition in mice with subcutaneous GL261 gliomas. In orthotopically inoculated patient-derived HSJD-DIPG-007 diffuse intrinsic pontine gliomas, notoriously known to have an intact BBB and poor drug responsiveness, we provide initial experimental evidence showing that multidrug micelles plus sonopermeation can help to improve treatment efficacy. Our work exemplifies that synergistic drug combinations can be efficiently co-loaded in polymeric micelles, and that advanced nanosonochemotherapy combination regimens hold promise for the treatment of hard-to-treat brain cancers.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433180","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

Outside Front Cover: Dali Chen et al

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/S0168-3659(25)00118-X

引用次数: 0

Black phosphorus nanosheets fortified with catalase to enhance Schwann cell responses for neural repair

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/j.jconrel.2025.02.017

Junjie Shen , Guoping Jia , Qinghe Wu , Huizhen Yang , Yifei Jiang , Xubo Wu , Yimin Chai , Chunfu Zhang , Jia Xu

{"title":"Black phosphorus nanosheets fortified with catalase to enhance Schwann cell responses for neural repair","authors":"Junjie Shen , Guoping Jia , Qinghe Wu , Huizhen Yang , Yifei Jiang , Xubo Wu , Yimin Chai , Chunfu Zhang , Jia Xu","doi":"10.1016/j.jconrel.2025.02.017","DOIUrl":"10.1016/j.jconrel.2025.02.017","url":null,"abstract":"<div><div>Peripheral nerve injuries (PNI) present a significant clinical challenge due to the complex cellular and molecular activities that hinder functional recovery. Schwann cells (SCs), the principal glial cells in the peripheral nervous system, play a vital role in neural repair by transitioning into a repairing phenotype capable of supporting axonal regrowth. However, these regenerative properties fade over time, leading to poor clinical outcomes. To address this issue, we engineered a black phosphorus nanosheet (BPNS) functionalized with catalase (BPNS@CAT) to modulate SC activity and enhance nerve regeneration. In vitro experiments demonstrated that BPNS@CAT reduced ROS levels, regulated the angiogenic and immunomodulatory functions of SCs. Mechanistically, we identified that BPNS@CAT activated the JAK/STAT pathway, which is crucial for SC-mediated repair processes. To validate its therapeutic potential, a BPNS@CAT-GelMA/PCL hydrogel scaffold was fabricated and applied in a rat sciatic nerve-crush model. The scaffold enhanced axonal regeneration, restored nerve function, and improved sensory, motor, and emotional behaviors. Our study broadens the range of BPNS applications in SC-based nerve repair and pave the way for future applications of BPNS in translational medicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages 579-598"},"PeriodicalIF":10.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408094","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

In vivo MRI of breast cancer using carbonic anhydrase IX proteoglycan-like domain -targeting liposomes.

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/j.jconrel.2025.02.032

Claudia Quattrociocchi, Sergio Padovan, Sharmila Fagoonee, Silvio Aime, Valeria Menchise, Daniela Delli Castelli

{"title":"In vivo MRI of breast cancer using carbonic anhydrase IX proteoglycan-like domain -targeting liposomes.","authors":"Claudia Quattrociocchi, Sergio Padovan, Sharmila Fagoonee, Silvio Aime, Valeria Menchise, Daniela Delli Castelli","doi":"10.1016/j.jconrel.2025.02.032","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.02.032","url":null,"abstract":"<p><p>Molecular imaging of breast cancer is increasingly recognized as a valuable tool for optimizing therapeutic interventions. Among potential targets for molecular imaging reporters, Carbonic Anhydrase IX (CAIX) stands out for its overexpression in tumors characterized by large hypoxic areas and aggressive phenotypes. CAIX, a transmembrane glycoprotein involved in pH regulation, displays a unique proteoglycan-like (PG) domain, not present in other isoforms, that could represent a specific target for imaging and therapy. While high sensitivity imaging techniques such as Positron Emission Tomography (PET) and optical imaging have been applied for CAIX targeting, no in vivo study utilizing Magnetic Resonance Imaging (MRI) to target CAIX has yet been reported. Herein, we address this gap by applying CAIX PG-targeting functionalized liposomes in the first in vivo MRI study on a murine model of breast cancer. TS/A cells were subcutaneously injected to generate primary tumors in mice, and targeted liposomes were delivered intravenously after 15 days. Internalization of the targeted liposomes by receptor-mediated endocytosis led to an enhanced MRI signal in the tumor region. Cytoplasmic and endosomal distribution of the liposomes' payload was observed. Conversely, non-functionalized liposomes and liposomes bearing a scrambled peptide, while entering tumor cells in smaller amounts, localized only to endosomes as expected. The findings reported herein suggest that CAIX PG domain-targeting liposomal formulations exploiting receptor-mediated endocytosis can lead to improved diagnostic capabilities and open avenues for targeted therapeutic delivery for the treatment of tumors overexpressing CAIX, particularly breast cancer.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433166","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

Content list including Graphcal Abstracts

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/S0168-3659(25)00123-3

引用次数: 0

Syncytial therapeutics: Receptor-specific and direct-to-cytosol biologic drug delivery mediated by measles fusion complex.

IF 10.5 1区医学

Journal of Controlled Release Pub Date : 2025-02-14 DOI: 10.1016/j.jconrel.2025.02.033

Victor A Garcia, Casim A Sarkar, Brenda M Ogle

{"title":"Syncytial therapeutics: Receptor-specific and direct-to-cytosol biologic drug delivery mediated by measles fusion complex.","authors":"Victor A Garcia, Casim A Sarkar, Brenda M Ogle","doi":"10.1016/j.jconrel.2025.02.033","DOIUrl":"https://doi.org/10.1016/j.jconrel.2025.02.033","url":null,"abstract":"<p><p>This work explores cell-cell fusion mediated by measles virus (MeV) as a potential new cell therapy modality that achieves direct-to-cytosol (DTC) drug delivery. MeV induces receptor-mediated fusion at the cell surface via its hemagglutinin (H) and fusion glycoproteins (F), bypassing endocytic membrane transport, and enabling direct cytosolic mixing between a fusogenic donor and host target cell. Fusion of this type gives rise to large syncytia formed by the inclusion of additional target cells over time. Fusion receptor specificity was first examined in CHO \"non-target\" and CHO \"target\" cells exogenously expressing the measles target SLAM (CHO-SLAM) by mono- or co-transfection of each cell type with plasmids encoding MeV-H and MeV-F. Fusion was observed only in CHO-SLAM cells which were co-transfected with both plasmids, which verified receptor-specificity without false-triggering of fusion in co-transfected \"non-target\" CHO or in MeV-F mono-transfectants of either cell type. Next, CHO donor cells with constitutive mCherry expression were co-transfected with MeV-H and MeV-F, and mCherry-positive syncytia were observed when cells were mixed with CHO-SLAM demonstrating the ability to deliver the mCherry payload via DTC. Increasing the cell dose does not affect the size distribution of resulting syncytia but contributes to a higher total mCherry delivery. Further, control of MeV stoichiometry can modulate the degree of syncytia formation and protein delivery, demonstrating that limiting MeV-H and increasing MeV-F favors fusion and cytosolic delivery. Taken together, these results demonstrate MeV cell-fusion-based, DTC delivery as a robust and tunable system for achieving targeted cytosolic delivery and controlled syncytia formation.</p>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433183","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