JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Min Gao,Yue Song,Jing Liang,Tiantian Chen,Jiajia Luo,Panyu Du,Han Wang,Hongyu Leng,Zheng Wang,Xinlong Ma,Kai Wang,Yanjun Zhao
Concurrent induction of apoptosis and ferroptosis is promising in handling heterogenous cancers. We report a tailored polymeric micellar nanoplatform for the combinational anti-tumor therapy. Two stimuli-responsive amphiphlic block copolymers were synthesized, bearing three functional moieties, i.e. azobenzene, nitroimidazole and 3-fluorophenylboronic acid. Azobenzene could enhance the cellular uptake of micelles. Nitroimidazole and 3-fluorophenylboronic acid could deplete the reduced nicotinamide adenine dinucleotide phosphate (NADPH), glucose and adenosine triphosphate (ATP) under hypoxia, sensitizing ferroptotic and apoptotic cell death. The proof-of-concept was demonstrated in a triple-negative breast cancer cell line (MDA-MB-231). Irrespective of the free or encapsulated form, doxorubicin and auranofin showed a synergistic action, evidenced by a low combination index (< 1). The co-delivery micelles showed improved potency than the single drug-loaded micelles in terms of the biomarkers of apoptosis ( e.g. caspase 3/9, cytochrome c and ATP) and ferroptosis ( e.g. thioredoxin reductase, thioredoxin, glutathione, NADPH, malondialdehyde and lipid peroxides). The apoptosis and ferroptosis induction ability of cargo-free micelles was proved. The in vivo efficacy was verified in the MDA-MB 231 tumor-bearing nude mice model. The current work offers a promising strategy of combinational anti-tumor drug delivery for potent induction of ferroptosis and apoptosis via the sensitization effect of vehicle in the hypoxic tumor.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Chemistry
·
2025
·
IF 6.7
Dawei Zhen,Yirong Qiao,Fengmao Liu,Xiaohui Liu,Shouhe Pan,Qingrong Peng
This work investigated the interaction between micelles of surface-active ionic liquids (SAILs) and the peptide drug HPV16E7 49-57 . Nine SAILs were designed, including 1-octyl-3-methyl imidazolium with glycinate ([C 8 mim][Gly]), lysinate ([C 8 mim][Lys]), aspartate ([C 8 mim][Asp]), leucinate ([C 8 mim][Leu]), or phenylalaninate [C 8 mim][Phe]; 1-ethyl-3-methyl imidazolium with oleate (C 2 mim][Ole]) or myristate ([C 2 mim][Myr]); and cholinium with oleate ([Cho][Ole]) or myristate ([Cho][Myr]). The CMC and micellar sizes of SAILs were compared for variation of SAIL constituents. UV–Vis spectroscopy, fluorescence spectroscopy, and solubility determination by HPLC found that the amino acid-based SAIL micelles had higher interaction abilities with the peptide drug than the fatty acid-based SAIL micelles. Their interaction abilities followed the order of [C 8 mim][Phe] > [C 8 mim][Asp] ≈ [C 8 mim][Leu] > [C 8 mim][Gly] > [C 8 mim][Lys] and [C 2 mim][Myr] > [Cho][Myr] ＞[C 2 mim][Ole] > [Cho][Ole], respectively. 1 H NMR analysis revealed that dissimilar solubilization patterns of the peptide in SAIL micelles and the varied interaction forces between SAIL hydrophilic heads and the peptide functional groups caused the different interaction abilities. [C 8 mim][Phe] micelles exhibited the strongest interaction ability due to the solubilization pattern between SAIL monomers and presence of phenyl group at the SAIL hydrophilic head. Furthermore, circular dichroism measurement showed conformational alteration of the peptide by the SAILs. This work lays a foundation for delivery of peptide drugs using SAILs.
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yanan Gao,Xue Hu,Haiying Zhang,Simin Chen,Jiaqi Yu,Deqiao Dong,Haihe Zhan,Bingmiao Gao,Dingguo Li,Zhenmiao Qin,Yan Liu
Myocardial infarction (MI) is a critical heart disease with a high mortality rate, posing a serious risk to human health. Injectable hydrogels possess considerable therapeutic promise for managing MI through the application of tissue-engineered scaffolds for cell delivery. However, the oxidative stress microenvironment of MI lesions leads to low cell retention and survival. In this study, a thermo-sensitive resveratrol micelles (RES-M) loaded chitosan hydrogel (RM-CH) was developed against oxidative stress injury in cardiomyocytes (CMs). RM-CH had better scavenging ability against DPPH and ABTS radicals compared to industry-standard ascorbic acid. RM-CH had good biodegradability, histocompatibility and cytocompatibility. The injection process of the hydrogel did not cause cell injury. DHE and DCFH-DA staining showed that it can improve the survival of CMs by fighting against the oxidative stress microenvironment. Live/Dead staining of CMs in hydrogels showed that the addition of RES-M could rescue cell survival under oxidative stress. Hence, this work highlights the potential clinical applications of RM-CH which may present an ideal scaffold material for injectable cardiac tissue engineering.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Siying Che,Gaoqiong Deng,Yaoyu Qi,Xiutan Peng,Haiyan Fu,Yuanbin She
Residues of organophosphorus pesticides (OPs) raise considerable concern, while achieving high enough detection sensitivity is still a challenge for on-site fluorescence techniques. Herein, we report a “double-end samplification” strategy by encapsulating a low-emission fluorescent ion probe [DCF][P66614]2 into a cetyltrimethylammonium bromide (CTAB) hydrophobic core to form ionic luminescent micelles. At the probe end, ionic liquid micelles locally concentrated the probes, achieving a 350-fold fluorescence enhancement. Benefiting from the strong fluorescence characteristics of DCFP@CTAB, the electron transfer effect between phoxim and DCFP@CTAB, and the fluorescence “turn-off” caused by phoxim, fluorometric and colorimetric methods for simple and sensitive determination of phoxim were proposed. At the analyte end, electrostatic interactions and hydrophobic micellar cavities enhanced phoxim adsorption, improving the fluorescence quenching efficiency by 149%. Under optimized experimental conditions, this sensing platform with a “turn-off” pattern achieves visual limits of detection of 1.7 × 10–7 M and 3.0 × 10–8 M for colorimetric and fluorescence patterns, respectively. Besides, to meet the demand for convenient detection of phoxim, a self-correcting portable paper-based device was constructed, which enabled on-site quantitative analysis of phoxim with a LOD of 0.3 μM. This work represents the first attempt to assemble an ionic liquid with a surfactant, effectively improving the sensitive detection of trace pesticide residues and providing a method for on-the-spot monitoring of food safety.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Haihan Sun,Jiansong Zhao,Boyuan Liu,Jingxin Gou,Haibing He,Yu Zhang,Tian Yin,Xiangqun Jin,Xing Tang
This study comprehensively investigated the effect of structural integrity on the oral delivery efficacy of mPEG- b -PCL polymeric micelles (PMs) using fluorescence resonance energy transfer (FRET) technology. During mucus penetration, the integrity loss of PMs resulted from the “hydration effect” of mucins and the “solubilization effect” of bile salts. Increasing surface PEG density or decreasing particle size <50 nm resisted the “hydration effect”, while shortening PCL chain or increasing aggregation number alleviated the “solubilization effect”. Fluorescence colocalization studies demonstrated that low surface PEG density and small particle size enhanced the cellular uptake of PMs, but high surface PEG density preserved the intracellular integrity of PMs. Approximately 30 %–60 % of endocytosed PMs were expelled within 4 h, correlating with their cellular uptake efficiency. Transcellular transport results indicated that 5 %–25 % of PMs underwent transcytosis within 4 h, 0.5 %–10 % of initial PMs remained intact. In situ intestine perfusion data confirmed the consistency between the in vitro findings and the actual performance of PMs in vivo . Two types of PMs were selected to encapsulate cyclosporine A (CyA) based on their enhanced integrity and transcytosis efficiency. The PM with a short amphiphilic block and loose structure exhibited comparable in vitro release and in vivo performance to Neoral®, with a C max of 1356.28 ± 170.01 ng/mL, a T max of 2 h, and an AUC 0-t of 16,408.92 ± 1166.78 ng/mL*h. However, the PM with a long amphiphilic block and ordered core PCL arrangement exhibited sustained release of CyA both in vitro and in vivo , decreasing CyA accumulation in major organs and improving the oral bioavailability of CyA, with a C max of 757.07 ± 66.19 ng/mL, a T max of 9.33 ± 2.31 h, and an AUC 0-t of 21,938.44 ± 2183.59 ng/mL*h.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jiajia Luo,Yaqi Shang,Ning Zhao,Xiaoying Lv,Zheng Wang,Xin Li,Xuan Meng,Yanjun Zhao
ABSTRACT Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn 2+ ) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn 2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. An SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn 2+ compared to that of histidine and Zn 2+ , such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing difficult-to-treat ovarian cancer.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Xiu-ying Li,Feng-yuan Zhang,Xin Wang,Qin-qing Li,Yan-dong Li,Cai-xia Liu
Inflammation and bone damage are the primary factors contributing to poor quality of life in patients with rheumatoid arthritis (RA). Triptolide (TP), the main active component of Tripterygium wilfordii , exhibits a certain inhibitory effect on RA, however, its clinical application is hindered by systemic toxicity and poor spatiotemporal specificity in vivo . Based on the pathological features of RA, we designed and constructed a novel multifunctional TP-loaded micelle (Mul@MC) with acid sensitivity and particle size shrinkage properties. Specifically, Mul@MC first accumulates at inflammatory sites via passive targeting. In the acidic microenvironment of RA lesions, acid-sensitive bonds on the micelle surface are disrupted, exposing folate ligands. This process is accompanied by a significant reduction in particle size, which the penetration of the formulation into inflamed joints. Subsequently, the exposed folate ligands enable active targeting of folate receptors (FR) overexpressed on M1 macrophages. This targeted delivery inhibits M1 polarization of macrophages, promotes M1 macrophage repolarization, reduces the secretion of pro-inflammatory cytokines, and decreases the release of nitric oxide (NO) and reactive oxygen species (ROS). Consequently, the inflammatory microenvironment is rebalanced, chondrocytes are protected, and the toxicity of TP to normal tissues is effectively alleviated. In conclusion, the Mul@MC designed in this study exhibit excellent in vivo spatiotemporal selectivity for TP delivery. By integrating anti-inflammatory and chondroprotective effects, Mul@MC exerts a significant anti-RA effect, providing new prospects for the clinical application of TP in RA treatment
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2016
·
IF 4.889
Yanjun Chen,Qiaoxin Yue,Gejing De,Jie Wang,Zhenzhen Li,Shuiming Xiao,Huatao Yu,Hai Ma,Feng Sui,Qinghe Zhao
Aim: Tumor metastasis is one of the leading causes of insufficient chemotherapy during cancer treatment. In this study, a poly(β-amino ester) derivate was developed to fabricate paclitaxel (PTX) entrapped pH-responsive copolymer micelles for inhibition of breast cancer metastasis. Materials & methods: PTX-loaded micelles were fabricated by thin film hydration method. The inhibition efficacy of the as-prepared micelles was evaluated on MDA-MB-231 cells and tumor bearing mice. Results: PTX-loaded micelles were successfully prepared. Such micelles could promote drug uptake and MDA-MB-231 cell deaths, and suppress tumor metastasis. Conclusion: The pH-responsive PTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor microenvironments with improved inhibitory effects on tumor metastasis.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Sen Xu,Mengyu Fan,Qimeng Ding,Yibin Wang,Muhammad Ismail,Weimin Ruan,Yan Zou,Dongya Zhang,Meng Zheng
RNA interference (RNAi) has emerged as a highly promising therapeutic strategy for glioblastoma (GBM), yet its clinical efficacy heavily relies on the success of delivery systems. Traditional vehicles, including cationic polymers, lipids, and inorganic nanoparticles, frequently encounter critical challenges such as cationic toxicity, poor blood-brain barrier (BBB) penetration, or poorly-defined structures that hinder their clinical translation. To overcome these challenges, we developed a novel, structurally-defined non-cationic siRNA-micelle system based on siRNA-docosahexaenoic acid (DHA) conjugates. These conjugates self-assemble into stable siRNA-micelles that exhibit prolonged blood circulation, enhanced cellular uptake, and efficient BBB penetration. Due to their non-cationic nature and the inherent safety profile of DHA, these siRNA-DHA micelles exhibit exceptional biocompatibility, potentially minimizing carrier-based toxicity. By simultaneously targeting epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGFA), the siRNA-micelles potently inhibited tumor progression and substantially extended survival in orthotopic GBM mouse models via dual-target modulation. This structurally-defined, non-cationic siRNA delivery platform represents a robust and clinically translatable strategy for GBM treatment, and holds considerable promise for the RNAi-based therapy of other neurological disorders.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lei Nie,Xiaoyue Ding,Yingsong Zhao,Peng Ding,Meili Zhao,Yuanna Sun,Yanfang Sun,Guohua Jiang
Multifunctional hydrogel dressings, with their robust antibacterial and anti-inflammatory properties, represent a great potential in biomaterials for wound care. Injectable and self-healing hydrogels that mimic the natural extracellular matrix of tissues offer a promising strategy for effective wound repair. This study designs a hydrogel based on the formation of a dynamic cross-linking network within the hydrogel matrix through the Schiff base reaction between the synthesized polymers L-hydroxyproline-conjugated chitosan (LHCS) and oxidized pullulan (OPL). The fabricated LP hydrogels preserve the porous interconnected microstructure, excellent self-healing capacity, and injectability, suitable swelling capability, robust mechanical strength, and outstanding tissue adhesion. Moreover, curcumin was encapsulated in Polyether F127 (Pluronic F127) micelles to obtain curcumin loaded PF127 (Cur-PF127) micelles and then incorporated into LP hydrogel to fabricate the composite hydrogels. The composite hydrogels exhibit effective antibacterial properties and antioxidant abilities, admired hemostatic effect and hemocompatibility, excellent cytocompatibility and cell pro-migration ability. In addition, in vivo evaluation confirmed that curcumin loaded hydrogels could facilitate the regeneration of epithelial and hair follicles, increase the collagen production, alleviate the inflammatory response via the downregulation of the tumor necrosis factor-α (TNF-α), and reduce the fibrosis, thus promote the wound repair process. This work offers a promising facile approach for the development of the composite hydrogel as wound dressing in wound healing applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2025
·
IF 3.9
Haiqian Zhao,Fang Chen,Minghong Feng,Wenjing Lin,Hangbo Yue,Jianwei Guo,Chufen Yang
To improve the stability and drug-controlled release capability of folic acid-modified pH-responsive polymeric mixed micelles FA-PEG-PHEMA-PDEAEMA (FA-P1)/PCL-PHEMA-PPEGMA (P2), the hydroxyl termini of the PHEMA blocks in polymers FA-P1 and P2 were esterified with selenooctanoic acid (SA) to produce FA-P1-SA and P2-SA, which were capable of self-cross-linking and exhibited reduction responsiveness. Thus, folic acid-modified dual-responsive diselenide-containing mixed cross-linked micelles composed of FA-P1-SA and P2-SA were constructed and employed for the delivery of doxorubicin (DOX). Structural characterization by 1H NMR, FT-IR, Raman spectroscopy, and GPC confirmed successful SA conjugation at an esterification degree of approximately 70%. Experimental and dissipative particle dynamics (DPD) analyses showed that the DOX loading content and encapsulation efficiency of the FA-containing mixed cross-linked micelles (MCLM@DOX) (1:1 mass ratio of FA-P1-SA/P2-SA) were slightly lower than those of non-cross-linked micelles (MMSA@DOX), yet afforded superior retention under physiological conditions (16.11% vs 22.49% release at 120 h) and rapid, stimuli-triggered release (75.20% vs 83.32%) in reductive, acidic conditions. Cytotoxicity assays indicated minimal polymer toxicity after SA modification. Furthermore, FA-containing MCLM@DOX exhibited relatively good tumor-targeting and anticancer efficacy compared with FA-free counterparts (MCLM1@DOX).
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Jinfeng Dou,Haiqun Zhang,Xiuju Liu,Mengyu Zhang,Guangxi Zhai
A mixed micelle that comprised of monomethylol poly(ethylene glycol)-poly( d , l -lactic acid) (MPP), d -α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and stearic acid grafted chitosan oligosaccharide(CSO-SA) copolymers was developed to enhance the oral absorption of docetaxel (DTX). DTX-loaded MPP/TPGS/CSO-SA mixed polymeric micelles (MPMs) were prepared with thin film hydration method and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, critical micellization concentration, and in vitro stability in media modeling physiological conditions. The in vitro release of docetaxel from the mixed micelles was studied with dialysis method. The oral bioavailability studies were conducted in rats and the pharmacokinetic parameters were evaluated. The results showed that DTX-loaded MPP/TPGS/CSO-SA MPMs had a mean diameter of 34.96 nm and exhibited spherical shape under transmission electron microscopy. The drug loading of DTX in the mixed micelles was 19.15%. The critical micellization concentration of MPP/TPGS/CSO-SA copolymer was 2.11 × 10 −5 M, and the size of mixed micelles in gastric fluid (pH 1.6) for 2 h and simulated intestinal fluid (pH 6.5) for 6 h showed no significant change. The in vitro release study showed that DTX-loaded MPP/TPGS/CSO-SA MPMs exhibited slower release characteristics compared to DTX solution. The oral bioavailability of the DTX-loaded MPP/TPGS/CSO-SA MPMs was increased by 2.52 times compared to that of DTX solution. The current results encourage further development of DTX mixed polymeric micelles as the oral drug delivery system.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）