INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Lin Yue,Meihong Zheng,Imran Mahmood Khan,Zhouping Wang
The development of antibacterial agents with high bacteria-binding capability and antibacterial efficiency is highly desirable. Herein, cationic polysaccharide chitosan (CS) was combined with photosensitizer Chlorin e6 (Ce6) to construct a novel photodynamic antibacterial agent (CS-Ce6 conjugates) for combating gram-positive bacteria Staphylococcus aureus (S. aureus) and gram-negative bacteria Escherichia coli (E. coli) . CS-Ce6 conjugates with different degrees of substitution (DS) were synthesized and characterized by a spectroscopic method and organic elemental analysis to understand the relationship between structure and antibacterial effect. CS-Ce6 conjugates revealed good reactive oxygen species (ROS) generation ability and photodynamic antibacterial effect. Meanwhile, they both were positively correlated with DS in the range of 4.81% ~ 11.56% resulting in stronger photodynamic antibacterial ability. These findings highlight that CS-Ce6 conjugates have the potential as an effective photodynamic bactericidal agent in the antibacterial field.
研究领域:
微生物学
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药学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 30
·305709
·
IF 3.551
Xuemei Wang,Xin Ding,Bing Yu,Xiaoming Zhang,Youqing Shen,Hailin Cong
Cancer treatment has always been a big problem for people. With the application of photodynamic therapy, the problem has been alleviated. However, the problem of tumor hypoxia affecting photodynamic therapy has been waiting to be resolved. Therefore, we report here that a redox nanocarrier (called RN) is prepared by hollow mesoporous silica sphere (HMSNs) and a redox-responsive polymer ligand. The nanocarrier is loaded with metformin and catalase, and the polymer is linked to the photosensitizer chlorin e6 (Ce6). Metformin inhibits the mitochondrial respiration of cancer cells, reducing the activity of cancer cells and increasing the oxygen concentration required for photodynamic therapy. Not only the effect of photodynamic therapy is enhanced, but also the effect of chemotherapy is increased to achieve super additive treatment. These RNs exhibit not only low cytotoxicity but also high biocompatibility in vitro experiments. In vitro Ce6 release studies have shown a higher release in the presence of glutathione (GSH). Confocal microscopy can further indicate that the nanoparticles are carried to the area around the nucleus of the cancer cells. In addition, treatment with a mouse tumor model demonstrated that RN has an effective therapeutic effect on tumors.
研究领域:
生物医学工程
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肿瘤学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Xin Zhou,Pengbo Zhang,Haibo Ding,Hao Wang,Zhongze Gu
The persistent and recurrent nature of biofilm infections, coupled with their increased resistance to antibiotics, poses a significant health risk. Photodynamic therapy has emerged as a promising strategy against biofilms, and it is crucial to fully harness the optimal potential of photosensitizers for generating reactive oxygen species (ROS) in order to prevent the development of resistance through insufficient ROS induction. The present study describes the fabrication of a photodynamic platform through the conjugation of photosensitizer chlorine e6 (Ce6) into inverse opal photonic crystal (IOPC) with a matching photonic band edge. The resulting slow photon effect of IOPC improves the light-harvesting capacity of Ce6 and ensures a 370% enhancement in the production of high levels of ROS at low Ce6 dosage (nanomolar levels) and light intensity (3 mW cm −2 ). In vitro experiments demonstrate that IOPC enhances the photodynamic antibiofilm efficacy of Ce6 by an impressive 375%. Furthermore, in vivo experiments confirm that IOPC expedites wound healing in mice infected with biofilm through photodynamic treatment. This work provides valuable insights into the phenomenon of slow photon effect in enhancing photodynamic therapy and presents a recommended design principle for achieving efficient antibiofilm treatment.
研究领域:
医学
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生物学
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纳米技术
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产品关联
DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Hang Hu,Ting Yuan,Jiahao Qian,Xinya Lu,Xi Chen,Xiaoya Sun,Yuchen Lin,Yuxiang Tang,Qingbo Xu,Tianyu Zhu,Yu Hu,Defeng Xu
Photodynamic therapy attracts great attention in cancer treatment due to its minimal invasiveness, good tolerance and specific cancer targeting. However, most of tumors are hypoxic and the tumors will become more hypoxic after photodynamic therapy, which might cause the poor prognosis by inducing tumor angiogenesis. In the present work, polyethylene glycol modified protamine-chlorin e6 conjugate (PEG-protamine-Ce6) was synthesized for enhanced cancer photodynamic therapy. PEG-protamine-Ce6 was synthesized by conjugating protamine with methoxypolyethylene glycol acetaldehyde and Ce6 sequentially. The in vitro studies show that PEG-protamine-Ce6 self-assembles into nanoparticles in aqueous solution with uniform size (∼200 nm), positive zeta potential and spherical morphology. The in vitro cell studies show that PEG-protamine-Ce6 nanoparticles exhibit enhanced cellular uptake amount, intracellular ROS level elevation upon laser irradiation, cell apoptosis and photocytotoxicity as compared to Ce6. The in vivo studies show that PEG-protamine-Ce6 nanoparticles exhibit enhanced antitumor effect as compared to Ce6 upon laser irradiation. PEG-protamine-Ce6 with laser irradiation not only inhibits tumor cell proliferation, but also inhibits tumor angiogenesis by suppression of VEGF expression, whereas Ce6 with laser irradiation promotes tumor angiogenesis by enhancing VEGF expression. PEG-protamine-Ce6 nanoparticles developed in this work offer a novel nanomedicine for enhancing cancer photodynamic therapy.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
高影响因子
LASER PHYSICS LETTERS
·
2016
·Vol. 13
·期 9
·095602
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IF 2.391
Jing Wang,Xiongwei Wang,Shimiao Wang,Zheng Huang,Jun Liu
Chlorin e6 (Ce6), a large heterocyclic aromatic molecule, is a promising photosensitizer for photodynamic therapy (PDT). We propose an efficient nano-photosensitizer delivery system based on covalent interactions between Ce6 and polyethylenimine (PEI) coated carbon nanodots (CDots). We observed >50% Ce6 drug loading content for PEI, due to this compound's unique 'proton sponge effect.' We found that the covalently incorporated Ce6 molecules retained their functional properties for near-infrared (NIR) fluorescence imaging and PDT. The chemical characteristics of CDot-PEI-Ce6 and Ce6 were evaluated using different analytical methods, including transmission electron microscopy and UV–Visible absorption spectra. Time-correlated single photon counting (TCSPC) and fluorescence spectra were used to demonstrate that Ce6 successfully conjugated to the CDots. The high cellular uptake of CDots-PEI-Ce6 was confirmed using flow cytometry and confocal laser scanning microscopy. According to the MTT assay, the CDots-PEI-Ce6 exhibited low dark toxicity and efficient PDT efficacy to HeLa cancer cells. These results indicate that CDot-PEI-Ce6 conjugates are potential photosensitizer delivery systems for PDT.
研究领域:
生物医学工程
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肿瘤学
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
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2021
·
IF 0
Baoqu Zhang,Hongjun Yan,Zhouting Meng,Peiyuan Li,Xiantao Jiang,Zihua Wu,Jun-An Xiao,Wei Su
The global rise of antibiotic resistance of pathogenic bacteria has become an increasing medical and public concern, which is further urging the development of antimicrobial channels for treating infectious diseases. The combination of photodynamic therapy (PDT) with photothermal therapy (PTT) has been considered as a promising alternative way for the replacement of traditional antibiotic therapy. In this research, the newly fabricated Chlorin-e6 (Ce6) conjugated mesoporous silica-coated AuNRs, designated AuNR@SiO2-NH2-Ce6, exhibited synergistic photothermal effects and single oxygen localized generation property, and showed stronger photoinactivation for bacteria compared with Ce6. AuNR@SiO2-NH2-Ce6 can anchor to the cell membrane and accumulate in the interior of cells. Furthermore, the unique porous structure of AuNR@SiO2NH2 enabled Ce6 encapsulation in the mesopores and was subsequently released and activated by photothermic effect, allowing the generated single oxygen to penetrate into the cytoplasmic membrane or directly enter the interior of bacteria cells, thus overcoming the inherent defects of single oxygen. AuNR@SiO2-NH2-Ce6 not only damaged the integrity of the cell membrane of bacteria but also facilitated the cellular permeation and accumulation of external nanoagents in the bacteria upon light irradiation. In addition, AuNR@SiO2-NH2-Ce6 exhibited negligible cytotoxicity toward mammalian cells and hemolytic activity. Therefore, AuNR@SiO2-NH2-Ce6 may be highly promising candidates as topical antibacterial agents, and this study has wide implications on the design of next-generation antimicrobial agents.
研究领域:
生物医学工程
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微生物学
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纳米医学
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产品关联
DOI
PubMed
ACS Infectious Diseases
·
2025
·
IF 3.8
Feiyang Xu,Ting Cui,Zhendong Long,Haidong Shen,Hong Xie,Hongfu Liu,Jianfei Xie,Kai Yang,Yugui Tao
The development of drug-resistant biofilms has resulted in treatment failures for multidrug resistant (MDR) bacteria, presenting a substantial challenge to global public health. Consequently, the development of antibacterial agents has become an urgent priority. To overcome the limitations of poor penetration and inadequate efficacy of single-modal treatments for MDR bacterial biofilm infections, this study developed a Ce6/SFP nanocomposite system utilizing silk fibroin and polydopamine. The nanoparticles, fabricated via a desolvation-in situ polymerization method, demonstrated pH-responsive drug release properties. When subjected to an 808 nm NIR laser, the material exhibited a photothermal conversion efficiency of 29.3%. Furthermore, when paired with singlet oxygen produced through 660 nm excitation, it was highly effective in eliminating MDR Escherichia coli and MDR Staphylococcus aureus. The synergistic effect of photothermal therapy (PTT) and photodynamic therapy (PDT) disrupted the stability of the cell membrane and enhanced the antibacterial efficacy. Experimental results showed that the photothermal effect increased biofilm permeability, significantly improving Ce6 penetration depth. Moreover, in vivo treatments exhibited accelerated wound healing. Biocompatibility assessments revealed a hemolysis rate below 5% and no pathological damage to major organs. This study proposes a synergistic strategy to effectively address the challenges posed by biofilms and bacterial resistance.
研究领域:
医学
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材料科学
·
生物工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Zhiwei Li,Chao Wang,Liang Cheng,Hua Gong,Shengnan Yin,Qiufang Gong,Yonggang Li,Zhuang Liu
Magnetic targeting that utilizes a magnetic field to specifically delivery theranostic agents to targeted tumor regions can greatly improve the cancer treatment efficiency. Herein, we load chlorin e6 (Ce6), a widely used PS molecule in PDT , on polyethylene glycol (PEG) functionalized iron oxide nanoclusters (IONCs), obtaining IONC–PEG–Ce6 as a theranostic agent for dual-mode imaging guided and magnetic-targeting enhanced in vivo PDT. Interestingly, after being loaded on PEGylated IONCs, the absorbance/excitation peak of Ce6 shows an obvious red-shift from ∼650 nm to ∼700 nm, which locates in the NIR region with improved tissue penetration. Without noticeable dark toxicity, Ce6 loaded IONC–PEG (IONC–PEG–Ce6) exhibits significantly accelerated cellular uptake compared with free Ce6, and thus offers greatly improved in vitro photodynamic cancer cell killing efficiency under a low-power light exposure. After demonstrating the magnetic field (MF) enhanced PDT using IONC–PEG–Ce6, we then further test this concept in animal experiments. Owing to the strong magnetism of IONCs and the long blood-circulation time offered by the condensed PEG coating, IONC–PEG–Ce6 shows strong MF-induced tumor homing ability, as evidenced by in vivo dual modal optical and magnetic resonance (MR) imaging. In vivo PDT experiment based magnetic tumor targeting using IONC–PEG–Ce6 is finally carried out, achieving high therapeutic efficacy with dramatically delayed tumor growth after just a single injection and the MF-enhanced photodynamic treatment. Considering the biodegradability and non-toxicity of iron oxide, our IONC–PEG–Ce6 presented in this work may be a useful multifunctional agent promising in photodynamic cancer treatment under magnetic targeting.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
✓ 已验证
DOI
PubMed
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
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Yingying Liao,Jiahui Ye,Luoyijun Xie,Longfei Mao,Jiangcun Wei,Chutong Liu,Jing Liang,Jianlong Zhou,Miaomiao Yuan,Zujie Qin
The theophylline derivative d17 is a candidate drug for nonsmall cell lung cancer (NSCLC) treatment previously developed by our group. However, it has the limitations of inadequate bioavailability, poor targeting, and insignificant therapeutic effect. Chemo-photodynamic synergistic therapy is a promising method of synergistic antitumor therapy. Herein, d17 and photosensitizer chlorin e6 (Ce6) were loaded into nanoparticles (NPs) via supramolecular self-assembly, which are self-assembled through π–π stacking and hydrogen bond interactions to form nanospheres with a size of about 85 nm and a surface charge of −33 mV. Compared with free Ce6, the d17–Ce6 NPs have good hydrophilicity and stability and can effectively accumulate in NSCLC tumor tissues due to the enhancement and retention effect. More significantly, the d17–Ce6 NPs can synergistically inhibit tumor growth compared with other treatment groups with no obvious toxicity. Taken together, the d17–Ce6 NPs may be an effective carrier-free nanodrug for the chemo-photodynamic synergistic treatment of NSCLC.
研究领域:
药学
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Feng Chan,Zhu Donglei,Chen Lv,Lu Yonglin,Liu Jie,Kim Na Yoon,Liang Shujing,Zhang Xia,Lin Yun,Ma Yabin,Dong Chunyan
The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.
研究领域:
癌症研究
·
药学科学
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治疗学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Peishan Li,Jiaxin Li,Jinmei Cheng,Junyi Huang,Jinhui Li,Jisheng Xiao,Xiaopin Duan
Liposomes, especially polyethylene glycol (PEG)-modified long-circulating liposomes, have been approved for market use, due to good biocompatibility, passive tumor targeting, and sustained drug release. PEG-modified long-circulating liposomes address issues such as poor stability and rapid clearance by the reticuloendothelial system. However, they still face challenges like hindering drug uptake by tumor cells and preventing tumor penetration. Inspired by the hypoxic tumor microenvironment, we constructed a hypoxia-responsive liposome (PAO-L) to enhance the intracellular uptake and photodynamic therapy (PDT) effect of chlorin e6 (Ce6). The intelligent hypoxia-cleavable PEG-AZO-OA (PAO) was prepared by coupling PEG and octadecylamine (OA) to hypoxia-sensitive azobenzene-4,4′-dicarboxylic acid (AZO) through amide reaction. The synthesized PAO was further incorporated into Ce6-loaded liposomes to enhance the circulation stability, while promote the tumor penetration and internalization by the responsive shedding of PEG from liposome surface upon reaching the hypoxic tumor tissue. PAO-L mediated PDT significantly inhibited the growth of B16F10 and 4T1 tumors, as well as lung metastasis of 4T1 breast cancer. The excellent therapeutic effect and good tolerability make PAO-L a promising candidate for enhanced PDT.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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