BIOMATERIALS
·
2018
·
IF 8.806
Jie Li,Chunyang Sun,Wei Tao,Ziyang Cao,Haisheng Qian,Xianzhu Yang,Jun Wang
Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo . However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NP Ce6&PTX to circumvent the aforementioned challenge. The TK-NP Ce6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d, l -lactic acid) (PEG- TK -PLA). We demonstrated that the high PEGylation of TK-NP Ce6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time . At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ , which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Yilun Luo,Sentao Hu,Yan Li,Lie Ma
The balance of macrophages in immune reaction is crucial to tissue repair. Despite some studies, responsive surfaces for immunomodulation regulated macrophage phenotypes by external stimuli, there would be limit to 2D and manual intervention. Here, to address these limitations, we developed an inflammation environment-responsive macrophage-laden hydrogel-filled scaffold for investigating the impact of matrix confinement on macrophages phenotypes adaptively. We fabricated gelatin scaffolds with controllable pore size and found that macrophages within smaller pores tend to anti-inflammation phenotype. We prepared poly (vinyl alcohol) (PVA)-based hydrogels which were crosslinked with phenylboronic acid (PBA) -based linkers. The hydrogels have the abilities of shear thinning, cell lading, and ROS-sensitive degradation. Then, a macrophages-laden hydrogel-filled scaffold was fabricated by filling the hydrogels into the porous scaffold under vacuum. With the degradation of the hydrogels under the overexpression of ROS in an inflammation environment, the macrophages were transferred from a state with strong matrix confinement to weaker ones. Meanwhile, with the change of matrix confinement, macrophages upregulated the expressions of Arg-1 and IL-10, and downregulated the expressions of IL-1β, TNF-α, and IL-6, indicating the polarization toward to anti-inflammatory phenotype. The inflammation environment-adaptive modulation of macrophages phenotypes in 3D provides a smart and biomimetic strategy for immunomodulation and regenerative medicine.
研究领域:
免疫学
·
组织工程
·
再生医学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xiaoya Hou,Hua Lin,Xiudi Zhou,Ziting Cheng,Yi Li,Xue Liu,Feng Zhao,Yanping Zhu,Peng Zhang,Daquan Chen
Although the clinical usage of drugs administration was raising, the application of nanoparticles encapsulating the hydrophobic drugs with plummy efficiency was very scarce for atherosclerosis (AS) treatment. In this work, a novel dual ROS-sensitive and CD44 receptors targeting amphiphilic carrier material, oligomeric hyaluronic acid-2′-[propane-2,2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (oHA-TKL-Fc), named HASF, was synthesized and characterized by 1 H-NMR spectra. Then, we combined curcumin (Cur) with HASF into nano-micelles ( [email protected] micelles) by self-assembling method. The resulting [email protected] micelles had the average size of 150.8 nm and zeta potential of -35.04 mV to maintain the will-defined spheroidal structure and stability. Importantly, the [email protected] micelles had ultrahigh entrapment efficiency (about 51.41 %). Moreover, in vitro release study, Cur release from [email protected] micelles was effective in the reactive oxygen species (ROS) condition, and the release rate was interrelated with the concentration of hydrogen peroxide (H 2 O 2 ). Further, fluorescence imaging showed that the [email protected] micelles could more selective access to Raw 264.7 cells than free Cur via oHA-receptor mediated endocytosis. The MTT assay attested the safety of amphiphilic carrier material HASF. Additionally, the results of in vivo Oil red O lipid staining studies showed that the lesion area of the aorta was reduced to 47.3±3.4 % with [email protected] micelles, compared with the lesion area of Cur group (63.2±2.7 %), [email protected] micelles had the more remarkable effect in reducing lesion area (*P < 0.05). Consequently, the novel dual ROS-sensitive and CD44 receptors targeting drug delivery system would become a promising strategy for atherosclerosis.
研究领域:
药学
·
纳米技术
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Chunyan Hou,Hu Bai,Zhaojie Wang,Yuanhao Qiu,Li-Li Kong,Feifei Sun,Dongdong Wang,Hong Yin,Xiaoli Zhang,Haibo Mu,Jinyou Duan
Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents. The in vitro transfection study of this nanosystem revealed improved intracellular accumulation of siRNA and excellent gene silencing efficacy comparable to that of conventional cationic liposome. Moreover, the mRNA expression of inflammatory cytokines was remarkably decreased by our nanosystem. Considering its biocompatibility, transfection efficacy, and anti-inflammatory capability, this co-delivery nanosystem proclaimed to be a promising combined therapeutic strategy for enhanced anti-inflammatory therapy.
研究领域:
药学
·
纳米技术
·
分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 41
·
IF 13.117
Di Liu,Gaofeng Shu,Feiyang Jin,Jing Qi,Xiaoling Xu,Yan Du,Hui Yu,Jun Wang,Mingchen Sun,Yuchan You,Minxia Zhu,Meixuan Chen,Luwen Zhu,Qiying Shen,Xiaoying Ying,Xuefang Lou,Saiping Jiang,Yongzhong Du
The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine–modified chitosan (SC) was synthesized as a potential AKI kidney–targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule–1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion–induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)–sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.
研究领域:
药学
·
肾病学
·
药物递送系统
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 9
·3706-3716
·
IF 5.251
Hang Liu,Wei Jiang,Qin Wang,Lifeng Hang,Yucai Wang,Yanmei Wang
Tumor hypoxia, which is indispensable to tumor propagation and therapy resistance, has been one of the most important factors influencing clinical outcomes. To modulate the hypoxia microenvironment, we herein developed reactive oxygen species (ROS)-sensitive arylboronic ester-based biomimetic nanocarriers co-encapsulated with a photosensitizer chlorin e6 (Ce6) and a hypoxia-activated prodrug tirapazamine (TPZp) for tumor-specific release and synergistic photodynamic chemotherapy. In order to bypass macrophage uptake and improve tumor penetration, the nanocarriers were further modified with the red blood cell membrane and iRGD peptide (denoted as NPs@i-RBMCe6+TPZp). After administration, NPs@i-RBMCe6+TPZp exhibited prolonged blood circulation, selective tumor accumulation and excellent penetration into the tumor interior. Upon light irradiation, ROS were generated by Ce6 for photodynamic therapy (PDT), which subsequently caused dissociation of the ROS-responsive nanocarriers. An enhanced therapeutic effect was further achieved through the activation of TPZp in the aggravated local hypoxia microenvironment. The synergistic cancer therapy based on NPs@i-RBMCe6+TPZp significantly suppressed tumor growth with negligible side effects. The biomimetic nanocarriers have great potential to overcome hypoxia-limited PDT, and significantly improve the anticancer efficacy by synergistic tumor-targeted PDT and hypoxia-activated chemotherapy.
研究领域:
癌症治疗
·
纳米医学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Qiang Chen,Chunjing Guo,Xiudi Zhou,Yanguo Su,Huimin Guo,Min Cao,Jing Li,Yue Zhang,Weiyi Zhao,Xin Gao,Shuqi Mi,Daquan Chen
Currently, very limited therapeutic approaches are available for the drug treatment of atherosclerosis(AS). H 2 S-donor is becoming a common trend in much life-threatening research. Several studies have documented that H 2 S-lyase is predominantly present in endothelial cells. N-Acetylneuraminic acid (SA), natural carbohydrate, binds specifically to the E -selectin receptor of endothelial cells. Meanwhile, recent studies related to Chondroitin sulfate have excellent target binding ability with CD44 receptor. We conjecture that the N-Acetylneuraminic acid and Chondroitin sulfate modified nanomicelles not only enhances the accumulation of the drug but also cleaves the H 2 S donor in the lesion, thus one stone two birds. Given these findings, we synthesized two kinds of nanoparticles, Carrier I (SCCF) and Carrier II (SCTM), for atherosclerosis to validate our guesses. Initially, S-allyl-L-cysteine and 4-methoxyphenylthiourea were used as H 2 S donors for SCCF and SCTM, respectively. After the introduction of ROS-sensitive groups. Then, micelles with N-Acetylneuraminic acid and Chondroitin sulfate were prepared to load rapamycin(RAP). Further, in atherosclerosis Oil Red O staining (ORO) results confirmed remarkable treatment effect with [email protected] and [email protected] Thus, we conclude that the effect of dual-targeting nanomicelles with ROS-sensitive H 2 S donor based on N-Acetylneuraminic acid and Chondroitin sulfate will have a better role in atherosclerosis.
研究领域:
药学
·
纳米技术
·
心血管疾病
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Qing Liu,Rui Cong,Jinping Yu,Xiaoxin Zhang,Jiasheng Tu,Yingchun Dong,Lei Jiang,Bin Chen
Periodontitis, the sixth most prevalent human disease, involves excessive ROS and mitochondrial dysfunction as key pathological drivers. However, therapeutic strategies simultaneously targeting both mechanisms for optimal regeneration remain scarce. To address this, we developed a ROS-responsive hydrogel (Gel) integrated with mitochondria-targeted liposomes encapsulating Coenzyme Q10 (CoQ10-MLip/Gel). The CoQ10-MLip combines CoQ10 (mitochondrial electron carrier) with arginine residues (mitochondrial-targeting motifs). The phenylboronic ester-based Gel degrades under high ROS, enabling controlled CoQ10-MLip release. Its self-healing properties and injectability ensure prolonged retention in periodontal pockets. This system effectively eliminated ROS, restored mitochondrial integrity, and significantly mitigated periodontal inflammation in vivo. The CoQ10-MLip/Gel platform thus offers a promising strategy for periodontitis treatment and potentially other chronic inflammatory diseases.
研究领域:
生物材料
·
纳米医学
·
牙周病学
·
药物递送系统
·
炎症性疾病
✓ 已验证
DOI
高影响因子
Journal of Functional Biomaterials
·
2025
·Vol. 16
·期 8
·304
·
IF 5.2
Kaixi Cui,Tianzheng Li,Yifei Ma,Chuanjin Zhang,Ke Zhang,Chao Qi,Kaiyong Cai
Ultrasound-responsive nanomaterials represent a promising approach for achieving non-invasive and localized drug delivery within tumor microenvironments. In this study, we developed a piezocatalysis-assisted hydrogel system that integrates reactive oxygen species (ROS) generation with stimulus-responsive drug release. The platform combines piezoelectric barium titanate (BTO) nanoparticles with a ROS-sensitive hydrogel matrix, forming an ultrasound-activated dual-function therapeutic system. Upon ultrasound irradiation, the BTO nanoparticles generate ROS—predominantly hydroxyl radicals (•OH) and singlet oxygen (1O2)—through the piezoelectric effect, which triggers hydrogel degradation and facilitates the controlled release of encapsulated therapeutic agents. The composition and kinetics of ROS generation were evaluated using radical scavenging assays and fluorescence probe techniques, while the drug release behavior was validated under simulated oxidative environments and acoustic fields. Structural and compositional characterizations (TEM, XRD, and XPS) confirmed the quality and stability of the nanoparticles, and cytocompatibility was assessed using 3T3 fibroblasts. This synergistic strategy, combining piezocatalytic ROS generation with hydrogel disintegration, demonstrates a feasible approach for designing responsive nanoplatforms in ultrasound-mediated drug delivery systems.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Yahong Liu,Longfei Miao,Yuying Guo,Renbin Yuan,Xuejiao Li,Xinxin Wang,Xiaona Lin,Hongqi Tian
Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)–poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen species-sensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)–poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage.
研究领域:
药学
·
辐射生物学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Carbohydrate Polymer Technologies and Applications
·
2023
·
IF 5.5
Zi-Dan Wang,Hu-Hong Peng,Dong-Qiang Lin,Yi-Xin Guan
Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H 2 O 2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.
研究领域:
药学
·
癌症研究
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·
IF 2.7
Yonghua Zhai,Lili Wu,Jie Gao,Jingsheng Zhou,Longhai Du,Xiaoda Fu,Yang Gao,Tinglin Zhang,Mengya Zhang,Weihong Lu,Yan Wu
Smart gene delivery vectors are gaining increasing attention in gene therapy, owing to their low cytotoxicity and intrinsic responsiveness. Our previously fabricated novel cationic brush polymer, comprising C Se bonds and tertiary amine EGIn- g -PDMAEMA, shows potential for gene transfection. In this study, its high efficiency for siRNA/pDNA transfection and low cytotoxicity in reactive oxygen species (ROS)-rich microenvironments is substantiated in vitro. Its superior binding capacity with siRNA/pDNA is confirmed by agarose gel electrophoresis assay. The threshold weight ratios for siRNA/pDNA migration delay are 15 and 3 (polymer-to-nucleic acid, w/w), respectively. Fluorescence microscopy and ribonucleotide reductase regulatory subunit M2 gene silencing essay verify the biodegradability and responsive control release of nucleic acids under hydrogen peroxide stimulation in Huh-7 cells. Compared with the gold standard, polyethylenimine 25 kDa, the target polymer displays superior transfection efficiency in ROS-rich tumor cells under serum-free conditions. Furthermore, the vector–nucleic acid complexes exhibit over 90% cell viability at a high concentration of 12 μg mL −1 and good colloidal stability in phosphate-buffered saline (PBS) and 10% fetal bovine serum-PBS for 24 h. The efficient control release and expression of nucleic acids in ROS environments and reduced cytotoxicity highlight the superiority of EGIn- g -PDMAEMA as a gene delivery platform for tumor gene therapy.
研究领域:
生物医学工程
·
基因治疗
·
材料科学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）