ACS Applied Polymer Materials
·
2025
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IF 4.7
Xinyi Tang,Abiao Li,Xiaohong Cheng,Ruyi Ren,Tiange Zhao,Xiaoli Zhang,Tianqi Qin,Zhiyong Cui,Yuanyuan Ding,Chenguang Liu
Oral probiotics are a multitarget regulatory strategy for treating ulcerative colitis (UC), but their viability is mainly affected by gastric acid and reactive oxygen species (ROS). Herein, a pH and ROS dual-responsive alginate-based hydrogel facilitating the delivery of epigallocatechin gallate (EGCG)-Mn nanoparticle-modified Lacticaseibacillus rhamnosus GG (LGG@EGCG-Mn) to the colon is constructed to treat UC. EGCG-Mn layer enhances LGG’s oxidative stress resistance by 6.28-fold. The dual-responsive alginate/thioketal hydrogel (SA-tK-Ca2+) protects LGG@EGCG-Mn from gastric acid with a 71.6% survival rate and releases it at colonic lesions, resulting in improved LGG@EGCG-Mn colon retention. In vivo, LGG@EGCG-Mn@SA-tK-Ca2+ effectively prevents and treats UC by increasing the expression of ZO-1 and Occludin to restore the intestinal barrier, mitigating colon inflammation, maintaining intestinal homeostasis, and facilitating the synthesis of short-chain fatty acids. This study overcomes the challenges of probiotic delivery across the barriers of harsh gastric pH and intestinal ROS, offering a more effective probiotic therapy for UC.
研究领域:
药剂学
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胃肠病学
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纳米技术
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微生物学
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药物递送
✓ 已验证
产品关联
DOI
高影响因子
Nano Research
·
2024
·
IF 9.5
Wang Ding,Jiang Qi,Shen Ruoyu,Peng Lijun,Zhou Wentao,Meng Tingting,Hu Fuqiang,Wang Jianwei,Yuan Hong
The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage. Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease (IBD). Oral administration is the most common route for intestinal diseases. In this study, a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment, which can interrupt the pathological process of IBD, resulting in the significantly improved efficacy of existing treatments. Based on the specific pH values and high reactive oxygen species (ROS) levels in inflammatory sites of IBD, an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed, and confirmed in vitro and in vivo . The antiinflammatory drug dexamethasone acetate (Dex) and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions (TJs). The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis. In brief, a drug delivery system and a therapeutic strategy for IBD are successfully developed.
研究领域:
药学
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纳米技术
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炎症性肠病
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Xiaoxiao Hu,Mo Zhang,Cuilu Quan,Saisai Ren,Wei Chen,Jing Wang
Immunogenic cell death (ICD) represents a modality of apoptosis distinguished by the emanation of an array of damage-related molecular signals. This mechanism introduces a novel concept in the field of contemporary tumor immunotherapy. The inception of reactive oxygen species (ROS) within tumor cells stands as the essential prerequisite and foundation for ICD induction. The formulation of highly efficacious photodynamic therapy (PDT) nanomedicines for the successful induction of ICD is an area of significant scientific inquiry. In this work, we devised a ROS-responsive and triple-synergistic mitochondria-targeted polymer micelle (CAT/CPT-TPP/PEG-Ce6, CTC) that operates with multistage amplification of ROS to achieve the potent induction of ICD. Utilizing an “all-in-one” strategy, we direct both the PDT and chemotherapeutic units to the mitochondria. Concurrently, a multistage cyclical amplification that caused by triple synergy strategy stimulates continuous, stable, and adequate ROS generation (domino effect) within the mitochondria of cells. Conclusively, influenced by ROS, tumor cell-induced ICD is effectively activated, remodeling immunogenicity, and enhancing the therapeutic impact of PDT when synergized with chemotherapy. Empirical evidence from in vitro study substantiates that CTC micelles can efficiently provoke ICD, catalyzing CRT translocation, the liberation of HMGB1 and ATP. Furthermore, animal trials corroborate that polymer micelles, following tail vein injection, can induce ICD, accumulate effectively within tumor tissues, and markedly inhibit tumor growth subsequent to laser irradiation. Finally, transcriptome analysis was carried out to evaluate the changes in tumor genome induced by CTC micelles. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Deteng Zhang,Jinxiao Song,Zhenghui Jing,Huan Qin,You Wu,Jingyi Zhou,Xinlong Zang
Background Hepatocellular carcinoma (HCC) is a serious global health concern, accounting for about 90% of all liver cancer instances. Surgical treatment is a fundamental aspect of HCC management; however, the challenge of postoperative recurrence significantly impacts mortality rates.Methods We have developed a pH and reactive oxygen species (ROS) dual stimulus-responsive drug delivery system (PN@GPB-PEG NPs) loaded with chemotherapeutic paclitaxel (PTX) and indoleamine 2.3-dioxygenase (IDO) inhibitor NLG919, for HCC chemoimmunotherapy. The physiochemical properties, such as particle size, zeta potential, morphology, and encapsulation efficiency, were characterized. Furthermore, we investigated in vitro cytotoxicity, cellular uptake and immunogenic cell death in tumor cells treated with our nanoparticles. In vivo biodistribution, antitumor effects and immune responses were assessed in an HCC mice model.Results PN@GPB-PEG NPs display pH-responsive properties with improved targeting abilities toward tumors and improved uptake by HCC cells. Upon exposure to oxygen peroxide (H2O2), the sophisticated design allows for rapid release of therapeutic agents. In this process, PTX induces immunogenic cell death (ICD), which activates the immune system to generate an antitumor response. Simultaneously, NLG919 works to inhibit IDO, mitigating the immunosuppressive environment. This combination strategy leverages the advantages of both chemotherapy and immunotherapy, resulting in a powerful synergistic antitumor effect. In a mouse model of HCC, our nanoparticles effectively inhibited the growth of primary and recurrent tumors.Conclusion These encouraging results highlight the potential of our nanocarrier system as an innovative therapeutic approach to address HCC primary tumor and postsurgical recurrence, providing hope for enhanced patient outcomes.
研究领域:
肿瘤学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Rui Ni,Lele Huang,Zhen Li,Wenli Zhang,Yajie Wang,Yan Shen,Jianxin Wang,Weigen Lu
Purpose To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug. Methods A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG 5% ). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging. Results ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the un-transformable preparations in three-dimensional (3D) tumor spheroids. Furthermore, synergetic penetrating enhancement was achieved by LST-loaded transformable LPNs in 4T1 and fibroblast cell mixed 3D tumor spheroids. The improved tumor penetration of LST-loaded transformable LPNs was observed in vivo, which could be due to their collagen inhibiting and size/shape transformable effect. Due to their enhanced penetrability, LST and PTX-loaded transformable LPNs demonstrated significant in vivo antitumor efficacy in comparison to other preparations. Conclusion The results confirmed the efficacy of M/LST-Lip/PTX-PEG 5% in tumor targeting, collagen inhibition in TME, and enhanced tumor penetration. This novel drug delivery system can therefore play a substantial role in improving the therapeutic efficacy of antitumor drugs combined with TME-improving agents.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Jianing Zhao,Longbing Ling,Wei Zhu,Tianhao Ying,Tao Yu,Mengmeng Sun,Xuan Zhu,Yuan Du,Leiming Zhang
Atherosclerosis (AS), a leading cause of death worldwide, involves chronic macrophage inflammation from its initiation to the emergence of complications. Targeting plaque inflammation by re-polarizing pro-inflammatory M1 to anti-inflammatory M2 could therefore provide a promising strategy to treat AS, but currently available anti-inflammatory drugs limit clinical outcomes. In this study, we found that kaempferol (KPF) is capable of potential anti-inflammation as a novel drug candidate, which has been scarcely reported. Building upon these findings, we fabricated a macrophage-biomimetic KPF delivery platform, abbreviated as [email protected] to potentiate therapeutic payloads, wherein the designed ROS-responsive Dextran- g -PBMEO NPs with π-π stacking were coated with macrophage membrane (MM) for effective target and accumulation in atherosclerotic lesions. Therapy of [email protected] afforded significant decrease in proliferating macrophage inflammation while went with the reduction of key pro-inflammatory cytokines and re-polarization M1 to M2 phenotype, inducing excellent anti-AS responses in ApoE −/− mice after i.p. delivery. The mechanism of [email protected] was further investigated and found it related to block the ROS/NF-κB signaling pathways. Together with as well demonstrated biosafety profiles, this proof-of-concept opens an instructive door for the study of KPF-mediated nanodrugs in treatment of AS based on biomimetic NPs.
研究领域:
药理学
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纳米技术
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心血管疾病
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炎症
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
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IF 9.5
Haifeng Lu,Qi Lu,Hongwu Sun,Zhongkun Wang,Xiang Shi,Yuling Ding,Xiang Ran,Jing Pei,Yubo Pan,Qunlin Zhang
Intracellular reactive oxygen species (ROS) are closely associated with cancer cell types. Therefore, ROS-based pattern recognition is a promising strategy for precise diagnosis of cancer, but such a possibility has never been reported yet. Herein, we proposed an ROS-responsive fluorescent sensor array based on pH-controlled histidine-templated gold nanoclusters (AuNCs@His) to distinguish cancer cell types and their proliferation states. In this strategy, three types of AuNCs@His with diverse fluorescence profiles were first synthesized by only adjusting the pH value. Upon the addition of various ROS, fluorescence quenching of three types of AuNCs@His occurred with different degrees, thereby forming unique optical “fingerprints”, which were well-clustered into several separated groups without overlap by principal component analysis (PCA). The sensing mechanism was attributable to the oxidation of AuNCs@His by ROS, as revealed by X-ray photoemission spectroscopy, Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Based on the ROS-responsive sensing pattern, cancer cell types were successfully differentiated via PCA with 100% accuracy. Additionally, the proposed sensor array exhibited excellent performance in distinguishing the proliferation states of cancer cells, which was supported by the results of the Ki-67 immunohistochemistry assay. Overall, the ROS-responsive fluorescent sensor array can serve as a promising tool for precise diagnosis of cancer, indicating great potential for clinical application.
研究领域:
癌症生物学
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纳米技术
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分析化学
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
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IF 10.633
Rong Shi,Haisheng Li,Xin Jin,Xue Huang,Zelin Ou,Xuanfen Zhang,Gaoxing Luo,Jun Deng
Engineering smart nano-therapeutics for re-epithelialisation of chronic wounds facilitates the wound healing process. However, due to excessive oxidative stress damage and persistent inflammation in diabetic wound microenvironment, the migration of stimulating epidermal cells in diabetic wounds represents a significant challenge. Here we synthesised P311-loaded micelles by self-assembly of P311 peptides and diblock copolymer poly (ethylene glycol)-block-poly (propylene sulfide) (PEG-b-PPS, denoted as PEPS) that have unique ability to transform an oxidative wound microenvironment into a proregenerative one while also providing cues for epidermal cell migration. The [email protected] showed an accelerated migration of epidermal cells via activation of the Akt signalling pathway , simultaneously suppressing the unfavourable oxidative wound microenvironment by scavenging reactive oxygen species (ROS), ultimately leading to the induction of an environment conducive to cell migration. Furthermore, the micelles were able to bypass the inhibitory effect of ROS on the Akt signalling pathway, thereby promoting epidermal cell migration. Additionally, we observed that diabetic wounds treated with [email protected] showed accelerated chronic wound healing, granulation tissue formation, collagen deposition and re-epithelialisation, thereby suggesting the efficacy of [email protected] as a promising nanoplatform for the treatment of chronic wounds. Statement of significance Based on the unique conditions of the diabetic wound microenvironment, a smart drug delivery system with ROS-responsive nanomaterials has been widely investigated to enhance diabetic wound healing. In our previous studies, we observed that P311 promotes epidermal cell migration to induce wound re-epithelialisation. However, the application of P311 suffers from its instability. Herein, we developed a therapeutic platform with P311-loaded micelles ( [email protected] ), which were synthesized by the self-assembly of P311 peptides and diblock copolymer poly (ethylene glycol)-block-poly (propylene sulfide) (PEG-b-PPS, denoted as PEPS). These micelles provide continuous migration signals for epidermal cells by ROS-trigged P311 release. Additionally, [email protected] scavenges excess ROS and provides a microenvironment that reduces inflammation, which could protect P311 from enzymatic degradation and improve the bioavailability of P311.
研究领域:
纳米技术
·
药学
·
伤口愈合
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生物材料
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2025
·
IF 5.1
Sha Liu,Lina Wang,Yupeng Wang,Lina Geng
Delayed healing of post-melanoma-resection wounds is prone to induce tumor recurrence. Therefore, postoperative wound management for tumor resection needs concurrently address anti-cancer activity and wound healing promotion. In this study, a multifunctional micelle-hydrogels (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which co-loaded with apigenin and BMS-202, into dodecyl-modified chitosan (DCS) based hydrogel via Schiff base linkages and hydrogen bonding interactions, for post-resection melanoma therapy. This micelle-hydrogel enables ROS-triggered drug release, thereby minimizing systemic toxicity. More importantly, the released apigenin exerts selective cytotoxicity against tumor cells and bacteria while inducing immunogenic cell death (ICD). When combined with co-released BMS-202, the formulation enhances anti-tumor efficacy without harming normal tissue cells. Moreover, the AB@MH is fabricated via a straightforward, crosslinker-free method, ensuring excellent biocompatibility and effective wound healing promotion. In the melanoma resection model, the AB@MH group exhibited marked suppression of tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yang Chen,Wenting Cheng,Hailong Tian,Yilin Wang,Weifeng He,Canhua Huang
Burns catastrophically compromise the skin barrier, driving impaired healing, infection susceptibility, and regenerative failure, primarily through dysregulated inflammation, immune dysfunction, and overwhelming oxidative stress. While reactive oxygen species (ROS) mediate essential host defense, their pathological excess necessitates targeted modulation for burn repair. We engineered a ROS-responsive nanoassembly (PTC@Cu NPs) for co-delivering chlorogenic acid (CGA) and copper ions (Cu 2+ ). Synthesizing the amphiphilic polymer mPEG-TK-CGA (PTC) via a ROS-cleavable thioketal linker enabled self-assembly with Cu 2+ into NPs. This system achieves triggered release specifically within high-ROS burn sites. CGA and Cu 2+ act synergistically to potently scavenge ROS, polarize macrophages to a pro-regenerative M2 phenotype, and thereby ameliorate oxidative damage, infection, and healing deficits in deep partial-thickness burns. In vitro and in vivo studies demonstrate PTC@Cu NPs significantly suppress apoptosis, enhance cell migration, exert potent antibacterial effects, and markedly accelerate healing. These comprehensive therapeutic benefits are mechanistically underpinned by dual ROS reduction and macrophage M2 polarization. Collectively, this platform presents a promising strategy for infected deep burn wounds by simultaneously targeting oxidative damage, microbial infection, and impaired tissue repair.
研究领域:
纳米医学
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烧伤修复
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炎症调控
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氧化应激
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免疫调节
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药物递送
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生物化学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
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IF 4.4
Kangyuan Hu,Xiuhua Li,Zhaodan Tan,Yan Shi
Ovarian cancer is the most common malignant tumor in women. Shikonin (SHK), an herbal extract from Chinese medicine, shows promise in treating ovarian cancer by inducing reactive oxygen species (ROS). However, its clinical use is limited by poor tumor targeting and low bioavailability, and its therapeutic potential is further compromised by the elevated levels of antioxidants such as glutathione (GSH) within tumor cells. In this study, a novel formulation of ROS-responsive micelles loaded with SHK was developed using hyaluronic acid-phenylboronic acid pinacol ester conjugation (HA-PBAP) for targeted therapy of ovarian cancer through disruption of intracellular redox homeostasis. The SHK@HA-PBAP exhibits targeted delivery to ovarian cancer cells through the interaction between HA and CD44 receptors. Upon internalization by cancer cells, the high levels of intracellular ROS triggered the degradation of SHK@HA-PBAP and simultaneously released SHK and generated GSH scavenger quinone methide (QM). The SHK and QM released from the SHK@HA-PBAP effectively induce the production of ROS and deplete intracellular GSH, leading to the disruption of intracellular redox homeostasis and subsequent induction of cell death. These characteristics collectively inhibit the growth of ovarian cancer. In vitro and in vivo studies have demonstrated that SHK@HA-PBAP micelles exhibit superior antitumor efficacy compared to free SHK in both A2780 cells and A2780 tumor-bearing mice. The ROS-responsive SHK@HA-PBA presents a promising therapeutic approach for the treatment of ovarian cancer.
研究领域:
药学
·
癌症生物学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Xitong Ren,Haochen Yao,Jiali Sun,Fuxin Xue,Linjie Cui,Yajun Xu,Kazuo Sakurai,Na Shen,Zhaohui Tang
Immune checkpoint blockade (ICB) therapy represents a promising approach widely embraced for its sustained efficacy upon activation of the body’s immune responses. Nonetheless, its effectiveness exhibits significant variability among patients, with a response rate below 30 %. A key limitation is the insufficient tumor infiltration and specific priming of CD8 + T cells. To address this, we develop ROS-responsive TLR7/8 nanoagonists {methoxy poly(ethylene glycol)- b -poly-[(N-2-hydroxyethyl)-aspartamide]- g -thioketal-R848}, designated as R848 NPs, wherein the C-4 amino of R848 is chemically blocked to enable selective release under endogenous tumor ROS conditions, thereby mitigating the severe systemic cytokine storms associated with R848. Additionally, ultrasound (US) is employed to induce immune cell death and facilitate intratumoral enrichment of R848 NPs. The proposed combination treatment, R848 NPs+US, effectively enhances antigen presentation by dendritic cells (DCs), facilitates intratumoral distribution of active R848, mitigates systemic inflammatory responses, promotes the release of damage-associated molecular patterns, and upregulates the expression of costimulatory molecules on DCs. Ultimately, R848 NPs+US plays a crucial role in bolstering CD8 + T cells immunity, synergizing with αPDL1 for CT26 tumor suppression (rate: 99.0 %, Q value: 1.68), eliciting memory immunity, and preventing tumor rechallenge. This work provides a novel strategy to potentiate the cancer immunity and a guidance for ICB therapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）