Journal of Physical Chemistry C
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2020
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IF 4.189
Lixin Zang,Huimin Zhao
Metalloporphyrins are suitable for medical oxygen sensing without disturbance to local tissue environment. To understand the correlation between the first triplet-state (T1) energy of metalloporphyrins and their phosphorescence responses to oxygen, the luminescence and oxygen sensing properties of two porphyrins (hematoporphyrin monomethyl ether, HMME; tetraphenylporphyrin, TPP) coordinated to gadolinium(III) (Gd) were studied comparatively. The absorption and luminescence of Gd-TPP are red-shifted relative to that of Gd-HMME, indicating that Gd-TPP has a lower T1 energy. The phosphorescence quantum yield (ΦP) of Gd-TPP is ∼10% of that of Gd-HMME. The large difference in ΦP is due to the increased nonradiative decay rate of T1 in Gd-TPP, as demonstrated by a shorter phosphorescence lifetime. The oxygen response (KSV) is related to the unquenched phosphorescence lifetimes (τ0) and oxygen quenching constants (kq) according to the equation KSV = τ0kq. KSV of Gd-HMME phosphorescence is larger than that of Gd-TPP. The larger kq of Gd-HMME stems from a better energy overlap between its T1 and the second excited state of oxygen, as demonstrated by its higher singlet oxygen quantum yield. Thus, the difference between the kq values of metalloporphyrins is another factor contributing to their diverse oxygen responses.
研究领域:
生物医学
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光化学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
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IF 5.999
Ying Xu,Peng Chen,Lei Tang,Xiaojun Zhang,Feng Shi,Xuyang Ning,Jingli Bi,Yang Qu,Hongfei Liu
Most chemotherapy agents have serious side effects due to lack of tumor targeting, which affects their clinical application. In addition, as an essential characteristic of malignant tumor, hypoxia is attracting exclusive research focus regarding its non-invasive real-time tracing in novel targeting delivery system. Herein, we designed a mixed micelle with tumor targeting and hypoxia responsiveness for tumor therapy and imaging. In particular, the dual-modified mix micelles were self-assembled by folic acid (FA) and 2-(2-nitroimidazole) ethylamine (NI) conjugated polymers , in which paclitaxel (PTX) and quantum dots (QDs) were co-loaded into the hydrophobic core. The drug loaded micelles showed satisfactory drug encapsulation, good storage stability, and sustained release properties. In vitro cell experiments showed that the mixed micelles exhibited enhanced cytotoxic effect and improved the cellular uptake, especially under hypoxic conditions, which was due to the FA mediated active targeting effect and NI induced hypoxic responsive release. In vivo experiments further proved that the mixed micelles possessed outstanding tumor targeting and hypoxia responsive properties. Furthermore, the drug loaded micelles showed excellent anti-tumor effect and can realize real-time in vivo imaging. This work demonstrates that the dual-modified mixed micelles co-loading with PTX and QDs might provide a novel approach for tumor therapy and imaging.
研究领域:
药剂学
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
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IF 15.7
Cong Rui,Deng Chengyu,Li Pengwei,Tang Yiwei,Hou Jinfan,Zhao Jiehui,Wang Qili,Chen Yingying,Tu Jiasheng,Jiang Xiqun,Jiang Lei
Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, which remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide (D-CuP) for diabetic wound treatment. The D-CuP is synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (M-CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biological stability against proteases, and broad biological activities. Meanwhile, the hydrogel matrix, exhibiting ROS-scavenging capabilities, has been engineered to be an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrates superior therapeutic efficacy, achieving 97.2% closure of infected wounds.
研究领域:
生物材料
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再生医学
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药剂学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Chemistry
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2018
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IF 0
Yan Zhang,Chuan Ma,Sihang Zhang,Chao Wei,Ying Xu,Wei Lu
Nowadays, the stability and on-demand release of drug carriers are still to be solved. To meet the demand of these issues, we developed a reactive oxygen species (ROS) responsive selenium-containing polyphosphoesters nanogel (PSeP) by a facile one-step ring-opening polymerization of the novel monomer 4-selenoctane-1,8-diyl bis(propylphosphatelane) (Se-COP) with polyethylene glycol (mPEG) employed as the macroinitiator. Their structure was confirmed by NMR, FT-IR and GPC. The crosslinked core-shell structure imparted the nanogels with excellent dimensional stability according to the dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the selenide groups endowed the nanogels with rich ROS responsiveness when subjected to the stimuli of H 2 O 2 , thus the drug-loaded PSeP nanogels displayed swollen behaviors leading to an activated doxorubicin hydrochloride (DOX · HCl) release. The release mechanisms fitted by the Ritger-Peppas power-law model also proved the swollen release process. MTT assays exhibited that the PSeP nanogels were nontoxic up to a tested concentration of 50 μg mL −1 by A549 and HEK293, and the DOX-loaded PSeP had a high anti-cancer behaviour against A549 cancer cells. Additionally, these nanogels possessed enhanced intracellular drug release by CLSM . Therefore, these results highlighted that the selenium-containing polyphosphoesters nanogels could be a potential platform for the ROS-sensitive drug delivery.
研究领域:
生物材料学
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
LANGMUIR
·
2018
·
IF 3.789
Shengran Li,Binggang Chen,Yangchun Qu,Xinxin Yan,Wenliang Wang,Xiaojing Ma,Bo Wang,Sanrong Liu,Xifei Yu
As one of the most promising therapeutic methods, gene therapy has been playing a more and more important role in treating disease due to its ultra-high therapy efficiency. Even if nonviral gene vectors represented by polycation, liposomal, dendrimers, and zwitterionic materials have made great progress in gene complexation, low immunogenicity, and biocompatibility, intracellular gene release with low toxicity is effectively still a bottleneck restricting the clinical application of gene therapy. We designed and synthesized a reactive oxygen species (ROS)-responsive dendrimer poly(amido amine)-N-(4-boronobenzyl)-N,N-diethyl-2-(propionyloxy)ethan-1-aminium (PAMAM-(B-DEAEP)16) as a gene vector whose potential can vary from positive to negative under the elevated ROS (H2O2) in cancerous cells. Dynamic light scattering results showed that the zeta potential of PAMAM-(B-DEAEP)16 decreased from +12.3 to −5 mV under 80 mM H2O2 in PBS buffer. The 1H NMR results demonstrated that the intermediate status of PAMAM-(B-DEAEP)16 was zwitterionic in ∼6 h because it consisted of the positive quaternary ammonium and negative carboxylic acid simultaneously before the ester bond was completely hydrolyzed. Gel retardation assay showed that PAMAM-(B-DEAEP)16 can condense DNA at above N/P = 1; then, PAMAM-(B-DEAEP)16 transfers to zwitterionic, which begins to continuously release DNA with the decrease in the positive charges and increase in the negative charges, and finally to negatively charged poly(amido amine)-propionic acid (PAMAM-PAc16) in the 80 mM H2O2. Fluorescence-labeled Cy-5 DNA indicated that PAMAM-(B-DEAEP)16 can enter into the cell completely in ∼4 h. The results showed that this compound we designed exhibited higher gene transfection efficiency and lower cytotoxicity than commercial PEI. This is the first time that the positively charged dendrimer was transferred to zwitterionic dendrimer under the stimuli of H2O2 and was successfully applied to gene delivery. Unlike all of the previous reports, we did not seek a compromise between the high gene transfection and low toxicity but find a new avenue to make the gene carrier not only have higher gene transfection efficiency but also exhibit lower toxicity by introducing stimuli-sensitive groups into the positively charged dendrimer to make it capable of adjusting the charge property according to the microenvironment. This study not only provides a good method to design materials for gene delivery but also opens a new perspective to understand the process of gene delivery.
研究领域:
生物医学工程
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基因治疗
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Hao Ying,Liu Tailuo,Zhou Hao,Xu Runhao,Li Ka,Chen Mao,Chen Yuwen
Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors.Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine–polyethylene glycol (DSPE–PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP).Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.
研究领域:
肿瘤学
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药剂学
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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 DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Lei Chen,Jiabao Liu,Chunxiang Gui,Ke mei,Xiaoshuang Dai,Yang Song,Daobing Jiang,Lian Deng,Junda Liu,Neng Qiu
Malignant tumors are one of the most dangerous types of diseases seriously threatening global health, and how to better treat them is a difficult issue for the medical community. Podophyllotoxin and its derivatives were known to have good antitumor efficacy. But their poor water solubility, toxicity to normal tissues, susceptibility to drug resistance, and low absorption by cancer cells have limited their clinical application. A striking feature of cancer cells compared to normal cells is the existence of intracellular overproduction of reactive oxygen species (ROS), frequently used as stimuli for drug release from nanocarriers. In this study, we developed a ROS responsive twin prodrug PPT-S-PPT, in which two podophyllotoxins (PPTs) were coupled by 3,3′-thiodipropionic acid via a thioether bond. PPT-S-PPT can form spherical nanoparticles with a mean diameter of about 200 nm in water. These self-assembled nanoparticles maintained good storage stability for up to 3 weeks. In vitro release study showed that H 2 O 2 can accelerate the drug release of PPT-S-PPT NPs in PBS. Both HPLC assay and fluorescence study showed that the intracellular uptake of PPT-S-PPT NPs was significantly higher than free drug or free fluorescence probe. The PPT-S-PPT NPs were up-taken by Hela cells via multiple endocytic pathways, and lipid rafts may play a greater role in the endocytosis of PPT-S-PPT NPs. In addition, the PPT-S-PPT NPs showed higher inhibitory effect (almost 14-fold) than free PPT against Hela cells after 24h treatment. The potent cellular inhibition effect of NPs might be due to the increased cellular uptake as well as the enhanced intracellular drug release resulting from the ROS responsiveness. Moreover, PPT-S-PPT NPs revealed favorable cytocompatibility and good hemocompatiblity. This carrier-free ROS-sensitive twin drug nanoassebly provides possibilities for the development of ROS-responsive prodrugs or dimer nanoparticles for efficient cancer therapy.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Wenliang Wang,Lin Lin,Xiaojing Ma,Bo Wang,Sanrong Liu,Xinxin Yan,Shengran Li,Huayu Tian,Xifei Yu
Living drug delivery system has been proposed as new concept materials because it is able to communicate with biological system, sense subtle changes in body microenvironment caused by disease, and then make rapid response to cure in the early stage of disease. Herein, taking full advantage of the tumor hypoxia physiology and successive effects of photodynamic therapy (PDT), we designed a new living delivery system via combining the PDT and hypoxia-responsive chemotherapy, abbreviated as Ce6-PEG-Azo-PCL. Then, according to the fact that oxygen can be converted into reactive oxygen species during irradiation of the photosensitizer, tumor cells could be killed after the poly(ethylene glycol) (PEG) conjugated photosensitizer chlorine e6 was irradiated at the tumor site. What is more, the continuous consumption of oxygen could further amplify the hypoxia condition of tumor and trigger the disassembly of hypoxia-responsive azobenzene bridges at the tumor site to release loaded chemotherapeutics drugs doxorubicin. The ongoing collaboration with PDT and hypoxia-responsive chemotherapy provided an integrated therapeutic effect in vitro and in vivo to suppress tumor growth.
研究领域:
生物医学工程
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肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2024
·
IF 2.6
Jingmou Yu,Mengqi Liu,Chao Zhang,Lizhen Cheng,Changchun Peng,Dengzhao Jiang,Wenbo Liu,Hongguang Jin,Jin Ren
Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yongming Wang,Yangcan Ming,Zhichao Yu,Zhenjin Xu,Minglang Zou,Cuiping Chen,Fang Luo,Da Huang,Na Wang,Zhenyu Lin,Zuquan Weng
The intracellular delivery of protein drugs via nanocarriers offers significant potential for expanding their therapeutic applications. However, the unintended activation of innate immune responses and inflammation triggered by the carriers presents a major challenge, often compromising therapeutic efficacy. Here, we present oligoethylenimine-thioketal (OEI-TK), a reactive oxygen species-responsive cationic polymer with intrinsic anti-inflammatory properties, to overcome this challenge. OEI-TK self-assembles electrostatically with bovine serum albumin (BSA) to form stable nanoparticles (OTB NPs) with excellent encapsulation efficiency. In vitro studies confirmed that OTB NPs retained OEI-TK’s antioxidant and anti-inflammatory properties, enhanced biocompatibility, and efficiently delivered BSA into cells. Furthermore, OEI-TK facilitated the intracellular delivery of β-galactosidase while preserving its enzymatic activity, demonstrating its potential for functional protein transport. These findings highlight OEI-TK as a promising platform with dual benefits of inflammation modulation and intracellular protein delivery, holding potential for the synergistic treatment of inflammation-related diseases.
研究领域:
药学
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生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Linzhu Su,Yuanfeng Li,Shuang Tian,Fan Huang,Yijin Ren,Cuihong Yang,Henny C. van der Mei,Henk J. Busscher,Linqi Shi
Antibiotic-loaded PEG/PAE-based micelles are frequently considered for eradicating infectious biofilms. At physiological pH, PEG facilitates transport through blood. Near an acidic infection-site, PAE becomes protonated causing micellar targeting to a biofilm. However, micellar penetration and accumulation is confined to the surface region of a biofilm. Especially matured biofilms also possess hypoxic regions. We here designed dual-responsive PEG/PAE- b -P(Lys-NBCF) micelles, responding to both acidity and low oxygen-saturation level in matured biofilms. Dual, pH- and hypoxia-responsive micelles targeted and accumulated evenly over the depth of 7- to 14-days old biofilms. Delineation demonstrated that pH-responsiveness was responsible for targeting of the infection-site and accumulation of micelles in the surface region of the biofilm. Hypoxia-responsiveness caused deep penetration in the biofilm. Dual, pH- and hypoxia-responsive micelles loaded with ciprofloxacin yielded more effective, synergistic eradication of 10-days old, matured Staphylococcus aureus biofilms underneath an abdominal imaging-window in living mice than achieved by ciprofloxacin in solution or single, pH- or hypoxia responsive micelles loaded with ciprofloxacin. Also, wound-healing after removal of window and its frame proceeded fastest after tail-vein injection of ciprofloxacin-loaded, dual, pH- and hypoxia-responsive micelles. Concluding, pH- and hypoxia-responsiveness are both required for eradicating mature biofilms and advancing responsive antibiotic nanocarriers to clinical application. Statement of significance pH-responsive antibiotic nanocarriers have emerged as a possible new strategy to prevent antimicrobial-resistant bacterial infections from becoming the leading cause of death. In this paper, we show that commonly studied, pH-responsive micellar nanocarriers merely allow self-targeting to an infectious biofilm, but do not penetrate deeply into the biofilm. The dual-responsive (acidic pH- and hypoxia) antibiotic-loaded micelles designed here not only self-target to an infectious biofilm, but also penetrate deeply. The in vitro and in vivo advantages of dual-responsive nanocarriers are most obvious when studied in infectious biofilms grown for 10 viz a viz the 2 days, usually applied in the literature. Significantly, clinical treatment of bacterial infection usually starts more than 2 days after appearance of the first symptoms.
研究领域:
药学
·
感染生物学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Ying Sun,Qimeng Wu,Quanyou Fu,Hailin Cong,Youqing Shen,Bing Yu,Hao Hu
Combination chemotherapy is a common strategy to enhance treatment efficacy and avoid multidrug resistance (MDR) in clinical practice. However, it is difficult to ensure the co-enrichment and reasonable ratio of synergistic drugs in the lesion site after intravenous administration. Integrating synergistic drugs into a nanocarrier can improve drug stability, targeting, drug loading, and importantly, ensure that synergistic drugs work at one destination. This study uses 10-hydroxycamptothecin (HCPT) to construct a polymeric prodrug micelle , and the demethylcantharidin (DMC) is proportionally encapsulated within the micelle. Triggered by reactive oxygen species (ROS), HCPT and DMC were released simultaneously from the co-delivery platform in tumor cells. DMC promotes abnormal cell division by inhibiting the synthesis of the cell cycle checkpoint kinase Protein phosphatase 2A (PP2A), leading to increased cell vulnerability to DNA damage, disordered replication, and death. The co-delivery platform exhibited satisfactory biosafety and antitumor efficacy in vivo . The proposed co-delivery platform may provide a valuable reference for the translation of clinical combination chemotherapy regimens into nano-drug delivery systems.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 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）