COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xiaoting Yu,Yannan Chen,Mingqian Tan
The controlled release of antioxidant substances at the intestinal oxidative damage site is crucial for alleviating intestine-related diseases. Herein, the novel ROS-responsive carrier was synthesized through simple amidation reaction between carboxymethyl chitosan (CMC) and methionine (Met), a natural organic compound containing ROS-responsive linkages (thioether). Initially, astaxanthin (AXT) nanoparticles (AXT 2 @CMT) with excellent stability and drug loading capacity (39.68 ± 0.23 μg/mL) were prepared by optimizing various reaction conditions. In the simulated high-concentration ROS environment of the intestine, CMT achieved a transition from hydrophobic groups (thioether) into hydrophilic groups (sulfone), which was conducive to the controlled release of AXT. In vitro cell experiments revealed that AXT 2 @CMT could effectively alleviate the oxidative damage in intestinal epithelioid cell line No. 6 (IEC-6 cell) caused by H 2 O 2 . This study achieved a straightforward preparation of ROS-responsive nanocarrier through food ingredients, offering a theoretical foundation for the controlled release of AXT at the intestinal oxidative damage site.
研究领域:
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2025
·
IF 3.9
Sheng Lin,Xia Cheng,Xiyi Chen,Jinxuan He,Wenxiu An,Qiufang Bai,Qixian Chen,Lie Ma,Jianhua Hu,Yue Wang,Xiabin Lan
The refinement of dynamic molecular mechanisms regulating mRNA release kinetics represents a critical frontier in advancing the synthetic mRNA delivery systems. This study details the synthesis of an intriguing ROS-responsive cationic block copolymer (pM-pBD) via reversible addition−fragmentation chain transfer (RAFT) polymerization, employing biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) and charge-reversible (2-acryloyl)ethyl(boronic acid benzyl)diethylammonium bromide (BD) as monomeric precursors. The synthesized copolymer facilitates electrostatic-driven self-assembly with anionic mRNA. Mechanistically, the pBD block exhibits ROS-mediated charge transition, enabling stimulus-dependent molecular decomposition and promoting mRNA payload liberation, thereby establishing spatial regulation of translational activity. Furthermore, intracellular ROS modulation experiments revealed that systemic ascorbic acid administration selectively enriches reactive oxygen species within tumor microenvironments. This redox microenvironment significantly amplifies pM-pBD nanocomplex-mediated mRNA expression by an order of magnitude across multiple carcinogenic cell lines, validating the ROS-responsive characteristics of our rationally designed delivery platform. In vivo studies demonstrated the highest mRNA expression levels in tumors when aided by ascorbic acid adjuvants, despite lower tumor accumulation of mRNA compared to renal and hepatic sequestration post intravenous administration of the pM-pBD nanocomplex. This spatial expression pattern correlates with ascorbic acid-mediated intratumoral ROS accumulation, which promotes cargo release and subsequent protein synthesis of approximately 6.4-fold enhancement. Our approach, integrating redox-responsive polymer design with organ-specific pharmacological modulation, signifies a transformative advancement in targeted nucleic acid delivery. By merging stimulus-responsive materials science with tumor microenvironment biology, this methodology provides a foundation for spatially controlled mRNA expression, presenting an innovative strategy for precision oncology applications.
研究领域:
生物材料
·
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Yaqin Tu,Wei Zhang,Guorun Fan,Chenming Zou,Jie Zhang,Nan Wu,Jiahui Ding,Wen Qing Zou,Hongjun Xiao,Songwei Tan
High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.
研究领域:
癌症治疗
·
药学科学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 7
·936
·
IF 4.9
Peng Chen,Zhihui Wang,Xinmo Wang,Junni Gong,Ju Sheng,Yufei Pan,Dandan Zhu,Xiaoxuan Liu
Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers,Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover,Fc-C8-AmD 8Aalso integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Innovative Food Science & Emerging Technologies
·
2025
·
IF 6.8
Yumeng Wang,Siyi Tang,Meili Xin,Zhiying Li,Guoli Ao,Xu Xie,Yihan Li,Zijing Li,Zeming Wang,Xilin Wu,Jinlong Tian,Bin Li
As a clinically prevalent condition, dysphagia substantially compromises the quality of life of patients and imposes substantial economic burdens on healthcare systems. In this study, a reactive oxygen species (ROS)-responsive cationic liposome and inulin hydrogel composite system was developed to deliver blueberry anthocyanins (ACNs). Mitochondria-targeting ACN-loaded liposomes with triphenylphosphonium (TPP) (TPP-Lip@ACNs) were prepared using the thin-film hydration method, and a hydrogel with 60 % inulin concentration, International Dysphagia Diet Standardisation Initiative (IDDSI) Level 5, was screened as the optimal carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that TPP-Lip@ACNs had a particle size of 101.5 nm, with structural disintegration under H₂O₂ stimulation due to the cleavage of thioketal (TK) bonds, demonstrating ROS-responsive characteristics. Scanning electron microscopy (SEM) revealed that the inulin hydrogel had a honeycomb-like porous structure, encapsulating liposomes and slowing down drug release, reducing the 12-h cumulative release rate from 90.20 % (free liposomes) to 65.67 %. The IDDSI testing classified the hydrogel as Level 5 (pureed) for safe swallowing. Rheological analysis highlighted the superior viscoelastic and self-healing capabilities of the system. In vitro digestion simulations confirmed the stability of the system in simulated gastric fluid (SGF) and intestinal fluid (SIF), with a triggered controlled release in simulated colon fluid (SCF). Cytotoxicity and hemocompatibility tests showed no significant impact on Caco-2 cell viability and hemolysis rates of <5 %, indicating high biocompatibility. These findings provide a novel strategy for designing functional pigment delivery systems and developing dysphagia-oriented diets.
研究领域:
生物材料学
·
药物递送系统
·
功能性食品科学
·
转化医学
·
老年医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Guiping Yuan,Yifan Zhang,Shiqun Shao,Zhuxian Zhou,Jianbin Tang,Jiajia Xiang,Youqing Shen
Drug self-delivery systems (DSDSs) have been extensively exploited to enhance drug loading capacity and avoid excipient-related toxicity issues. However, deficient tumor targeting, inferior tumor permeability, prominent burst release, and nonspecific subcellular distribution remain major obstacles. Herein, we reported a ROS-responsive amphiphilic prodrug (CPT-S-NO) synthesized by the conjugation of zwitterionic tertiary amine-oxide (TAO) moiety and hydrophobic camptothecin (CPT) through a thioether linkage, which formed a nanoparticulate DSDS in an aqueous solution. CPT-S-NO, compared with CPT-11 and the water-soluble TAO-modified CPT prodrug (CPT-NO), exhibited prolonged blood circulation, enhanced tumor accumulation, deep tumor penetration, efficient mitochondrial targeting, and ROS-activated drug release to induce mitochondrial dysfunction, corporately conducing to the superior antitumor efficacy in vivo. This TAO decoration strategy promises potential applications in designing multipotent DSDSs for various drugs.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Nano Today
·
2025
·
IF 10.9
Zhaochu Xu,Jiang Yu,Yingxi Zhang,Yue Wang,Wenxiao Li,Baoyue Zhang,Wenwen Cui,Yicheng Li,Yue Wang,Zimeng Yang,Yubo Liu,Xin Li,Yongjun Wang,Zhonggui He,Hongzhuo Liu
Cancer vaccine has emerged as a promising therapeutic paradigm for cancer therapy. However, the lack of tumor-associated antigens and abundant immunosuppressive factors seriously diminish the efficacy of immunotherapy, resulting in poor clinical benefits. In this report, we engineered a coordinated immunostimulatory nanoplatform, termed MP@PPS NPs, by physically combining reactive oxygen species (ROS)-responsive poly (propylene sulfide) nanoparticles loaded with the photosensitizer pyropheophorbide a (PPa) and stimulator of interferon genes (STING) agonist (MSA-2), to function as an in situ cancer vaccine to amplify immunotherapeutic outcomes. Excellent stability of MP@PPS NPs endowed prolonged drug circulation time and improved tumor accumulation, while their small size boosted deeper drug penetration within tumors. Crucially, upon laser irradiation, the MP@PPS NPs could generate abundant ROS, which induced tumor ablation, triggered immunogenic cell death to initiate an adaptive antitumor immune response and facilitated the local release of MSA-2, thereby promoting innate antitumor immunity through the cGAS-STING pathway. MP@PPS NPs markedly suppressed both primary and distant tumor progression, promoted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration, elicited robust antitumor immunity. Meanwhile, MP@PPS NPs treatment impeded the lung metastatic in conjunction with anti-PD-L1 treatment. This work holds significant promise for the synergistic photodynamic immunotherapy, and offers a crucial inspiration for addressing the problems of insufficient antitumor immunity and ineffective cancer treatments.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Yiyan Song,Ping Zhu,Zhihui Xu,Jin Chen
Multidrug resistance evoked by overusing pharmaceuticals of poor water solubility has posed a serious threat to public health, which urges the development of safe and efficacious therapeutic formulations. In this study, biomimetic nanospherical polydopamine (PDA) formed under mild conditions was modified using methoxypolyethylene glycol amine (m-PEG-NH2) to produce a polydopamine-based drug delivery platform. As characterized by various physicochemical methods, the PEGylated PDA with a uniform size distribution showed superior biocompatibility and efficient load capability for two hydrophobic anticancer drugs of paclitaxel and phytochemical curcumin, which exhibited synergistic cytotoxicity and a pH/ROS-responsive release behavior. Significantly, an enhanced effect of the encapsulated paclitaxel and curcumin was identified toward the drug-resistant A549/TAX cancer cells, which was correlated with the improved cellular internalization of hyperbranched PDA composites and distinctive cell cycle arrest of loaded drugs. The dual-drug-loaded spherical PDA nanocomposites hold enormous potential to tackle drug resistance from a chemotherapy perspective.
研究领域:
药学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Qingqing Pan,Xin Deng,Wenxia Gao,Jing Chang,Yuji Pu,Bin He
With the utilization of high concentration reactive oxygen species (ROS) in tumor microenvironment, PEG-doxorubicin (PEG-DOX) prodrug was synthesized via a thioketal moiety as the linker, which was ROS cleavable to trigger DOX release from the self-assembled prodrug nanoparticles. The in vitro ROS sensitivity of prodrug nanoparticles (NPs) was investigated in Fenton agent and H 2 O 2 , and the disassembly of NPs was more sensitive to Fenton reagent. After internalized in HepG2 cells via endocytosis, the cellular ROS consuming test revealed intracellular DOX release. The pharmacokinetics and biodistribution study demonstrated that the in vivo elimination of NPs was significantly improved and the NPs were passively targeted to tumor tissues via EPR effect. The ROS-responsive prodrug NPs exhibited excellent antitumor activity in HepG2 tumor-bearing nude mice, remarkably induced tumor cells apoptosis and reduced the systemic toxicity of DOX. Our study revealed the ROS responsive prodrug nanoparticle is an effective strategy to fabricate nanomedicine for cancer chemotherapy.
研究领域:
药物递送系统
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Qiao Luo,Nianlan Cheng,Yongqing Yang,Ni Shao,Tianqi Nie,Jifeng Chen,Cuiqing Huang,Siqi Zhang,Yanyu Huang,Chon Man Ieong,Xiaokai Zhang,Kuan Hu,Zeyu Xiao,Liangping Luo
Myocardial ischemia-reperfusion (I/R) injury is characterized by oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis, ultimately leading to chronic cardiac dysfunction and heart failure. Current therapeutic strategies that predominantly target single biological pathways exhibit limited long-term efficacy, underscoring the necessity for multi-targeted approaches. In this study, we developed a ROS-responsive hydrogel system, S1&FT/Lipo-QCFT, tailored to deliver drugs for treating various stages of myocardial I/R injury. This system timing of drug release to achieve rapid deployment at early intervention stages and maintain sustained release thereafter. Initially, the hydrogel platform quickly releases the molecular forms of the superoxide inhibitor S1QEL1.1 and tannic acid, specifically targeting the elevated ROS levels at the I/R site to alleviate early oxidative damage and encourage macrophage polarization toward the M2 phenotype. Subsequently, the system gradually releases anti-fibrotic agent FT011, encapsulated in lipid nanocarriers, which actively counters TGF-β1-induced fibrosis and forestalls adverse ventricular remodeling, thereby enhancing long-term cardiac repair. In vivo studies demonstrated that the S1&FT/Lipo-QCFT hydrogel significantly improved cardiac function and reduced adverse ventricular remodeling. This hydrogel system provides a promising multi-targeted therapeutic strategy for comprehensive myocardial I/R injury treatment with strong potential for clinical translation.
研究领域:
药理学
·
心血管医学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yuxuan Dai,Shenghan Gao,Zhi Zhang,Wan-Jie Du,Xinyu Bao,Yun Xu
Alzheimer's disease (AD) has displayed complex pathological features, in which oxidative stress and ferroptosis play important roles. The development of collaborative treatment methods aimed at multiple pathological factors is particularly important for effective alleviation of AD. In our research, a multifunctional delivery system (CART-CeO 2 )@HA was developed for the co-delivery of neuroprotective Cocaine- and amphetamine-regulated transcript (CART) peptides and antioxidant CeO 2 nanozymes encapsulated within an ROS-responsive nanogel. Under the stimulation of Aβ, (CART-CeO 2 )@HA exhibited effective relief for cell apoptosis, mitochondrial dysfunction and synaptic loss on account of ROS removal and ferrous ions chelation. With sufficient accumulation and sustained drug release in the brain of APP/PS1 mice, (CART-CeO 2 )@HA significantly reduced the levels of oxidative stress and ferroptosis, which facilitate the reduction of Aβ deposition and the repair of neuronal damage, jointly rescuing the cognitive impairment in APP/PS1 mice. These results verified the clinical potential of the multi-target delivery system in AD synergistic therapy.
研究领域:
神经科学
·
纳米技术
·
药剂学
·
生物医学工程
·
病理学
✓ 已验证
产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2019
·Vol. 19
·期 8
·1900112
·
IF 2.895
Zehong Xiang,Yanming Wang,Zhifang Ma,Zhirong Xin,Runhai Chen,Qiang Shi,Shing-Chung Wong,Jinghua Yin
Inflammation-associated thrombosis is a non-negligible source of mortalities and morbidities worldwide. To manipulate inflammation-associated coagulation, nanoparticles that contain anti-inflammatory polymer (copolyoxalate containing vanillyl alcohol, PVAX) and anti-thrombotic heparin derivative deoxycholic acid (Hep-DOCA) are prepared. The strategy takes advantage of the reducted side effects of heparin through heparin conjugation, achievement of long-term anti-inflammation by inflammation-trigged release of anti-inflammatory agents, and formation of PVAX/heparin-DOCA nanoparticles by co-self-assembly. It is demonstrated that the Hep-DOCA conjugate and PVAX are synthesized successfully; PVAX and Hep-DOCA nanodrugs (HDP) are obtained by co-assembly; the HDP nanoparticles effectively reduce the inflammation and coagulation without inducing lethal bleeding both in vivo and in vitro. The method provided here is versatile and effective, which paves new way to develop nanodrugs to treat inflammation-associated thrombosis safely.
研究领域:
药学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）