ACS Sustainable Chemistry & Engineering
·
2021
·
IF 8.198
Yong-E Gao,Shengxin Hou,Jiaqi Cheng,Xinyi Li,Yongqiong Wu,Yuran Tang,Yanke Li,Peng Xue,Yuejun Kang,Zhigang Xu,Mingming Guo
With the merits of noninvasiveness, flexibility of treatment, and nonsystemic toxicity, photodynamic therapy (PDT) holds great promise in fighting against malignant cancers. Issues with conventional PDT, including severe hydrophobicity of the majority of photosensitizers (PSs), poor accumulation at the tumor site, and potential long-term side effects, greatly attenuate its therapeutic efficacy. Nanotheranostic systems are thus expected to assist our battle against cancer. Herein, we rationally designed the silk sericin (SS) based nanoparticles (designated as SSC NPs), in which photosensitizer chlorin e6 (Ce6) was conjugated with water-soluble SS via simple amidation reaction, for enhanced imaging-guided PDT. Compared with free Ce6, the as-prepared SSC NPs showed enhanced intracellular uptake efficiency and penetrability into tumor spheres. Furthermore, the SSC NPs exhibited negligible cytotoxicity toward 4T1 cells in darkness, while presenting a remarkable anticancer effect under a reduced laser power density (660 nm, 100 mW cm−2), indicating their good biocompatibility and feasibility as PDT nanoagents. Following systemic administration in 4T1 tumor-bearing mice, the SSC NPs achieved superior accumulation in tumor sites in comparison with free Ce6, which might contribute to prolonged blood circulation of nanoscale drugs. In vivo studies revealed that SSC NPs suppress the growth of tumors more effectively compared to free Ce6 and did not induce apparent side effects to the treated animals. Taken together, these results indicate that the SSC NPs have an exciting opportunity as an alternative candidate for SS-based phototherapy of cancer.
研究领域:
纳米技术
·
癌症研究
·
治疗诊断学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Lin Yue,Meihong Zheng,Min Wang,Imran Mahmood Khan,Xiaowei Ding,Yin Zhang,Zhouping Wang
The development of new antimicrobial agents is important to combat infections caused by pathogenic bacteria. Herein, Hydroxypropyl chitosan (HPCS), a hydrophilic modified product of chitosan (CS), was employed as a carrier of the photosensitizer chlorin e6 (Ce6) through an amide bond to obtain the products (HPCS-Ce6 conjugates) with a degree of substitution (DS) ranging from 2.95% to 5.25%. The UV–vis absorption spectra and 1 H NMR spectra confirmed the successful synthesis of the products. The products have a better and more stable reactive oxygen species (ROS) generation capacity and higher bacterial affinity than Ce6. At a very low dose (1.8 μg/mL), the highest DS product (HPCS-Ce6-3) can effectively kill Staphylococcus aureus ( S. aureus ) under 660 nm irradiation. In addition, the HPCS-Ce6 conjugates showed high biocompatibility in the CCK-8 test. The HPCS-Ce6 conjugates could be a photodynamic antibacterial agent with good water solubility, high biocompatibility, and antibacterial activity .
研究领域:
生物化学
·
微生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Lin Zou,Yao Zhang,Nihad Cheraga,Oluwatosin David Abodunrin,Kai-Yun Qu,Li Qiao,Yu-Qing Ma,Li-Juan Chen,Ning-Ping Huang
Recently, photodynamic therapy (PDT) has been considered as a new strategy for atherosclerosis treatment. Targeted delivery of photosensitizer could significantly reduce its toxicity and enhance its phototherapeutic efficiency. CD68 is an antibody that can be conjugated to nano-drug delivery systems to actively target plaque sites, owing to its specific binding to CD68 receptors that are highly expressed on the surfaces of macrophage-derived foam cells. Liposomes are very popular nanocarriers due to their ability to encapsulate a wide range of therapeutic compounds including drugs, microRNAs and photosensitizers, and their ability to be surface-modified with targeting moieties leading to the development of nanocarriers with an improved targeted ability. Hence, we designed a Ce6-loaded liposomes using the film dispersion method, followed by the conjugation of CD68 antibody on the liposomal surface through a covalent crosslinking reaction, forming CD68-modified Ce6-loaded liposomes (CD68-Ce6-mediated liposomes). Flow cytometry results indicated that Ce6-containing liposomes were more effective in promoting intracellular uptake after laser irradiation. Furthermore, CD68-modified liposomes significantly strengthened the cellular recognization and thus internalization. Different cell lines have been incubated with the liposomes, and the results showed that CD68-Ce6-mediated liposomes had no significant cytotoxicity to coronary artery endothelial cells (HCAEC) under selected conditions. Interestingly, they promoted autophagy in foam cells through the increase in LC3-Ⅰ, LC3-Ⅱ expression and the decrease in p62 expression, and restrained the migration of mouse aortic vascular smooth muscle cells (MOVAS) in vitro. Moreover, the enhancement of atherosclerotic plaque stability and the reduction in the cholesterol content by CD68-Ce6-mediated liposomes were dependent on transient reactive oxygen species (ROS) generated under laser irradiation. In summary, we demonstrated that CD68-Ce6-mediated liposomes, as a photosensitizer nano-drug delivery system, have an inhibitory effect on MOVAS migration and a promotion of cholesterol efflux in foam cells, and thereby, represent promising nanocarriers for atherosclerosis photodynamic therapy.
研究领域:
药理学
·
纳米技术
·
心血管疾病
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DENTISTRY
·
2018
·
IF 3.77
Xiaolin Sun,Lin Wang,Christopher D. Lynch,Xueke Sun,Xue Li,Manlin Qi,Cui Ma,Chunyan Li,Biao Dong,Yanmin Zhou,Hockin H.K. Xu
Objectives The objectives of this study were to: (1) develop the multifunctional nanoparticles containing Chlorin e6 (Ce6), Coumarin 6 (C6) and Fe 3 O 4 nanoparticles (NPs); and (2) investigate the inhibitory effects of the nanoparticles via antibacterial photodynamic therapy (aPDT) against three species of periodontitis-related pathogens for the first time. Materials and methods Ce6 and C6 were co-loaded into the Fe 3 O 4 -silane core-shell structure to form multifunctional nanoparticles (denoted “Fe 3 O 4 -silane@Ce6/C6 MNPs”). The physical and chemical properties of nanoparticles were characterized. Biofilm properties of Streptococcus sanguinis , Porphyromonas gingivalis and Fusobacterium nucleatum were tested. Colony-forming units (CFU), live/dead assay, and metabolic activity of biofilms were determined to evaluate the aPDT function mediated by the Fe 3 O 4 -silane@Ce6/C6 MNPs. Fluorescence imaging and the targeted antibacterial effects were also investigated. Results Fe 3 O 4 -silane@Ce6/C6 MNPs showed superparamagnetic properties, chemical stability and water-solubility, with no cytotoxicity. Fe 3 O 4 NPs did not compromise the emission peaks of C6 and Ce6. The Fe 3 O 4 -silane@Ce6/C6-mediated aPDT had much greater reduction in biofilms than the control groups (p < 0.05). Biofilm CFU was reduced by about 4–5 orders of magnitude via Fe 3 O 4 -silane@Ce6/C6-mediated aPDT. The co-loading of Ce6 and C6 enabled the real-time aPDT monitoring by ratio emissions with the same wavelength. Fe 3 O 4 with magnetic field enabled the targeting of infection sites by killing bacteria via magnetic field. Conclusion The multifunctional nanoparticles exerted strong anti-biofilm activity against periodontitis-related pathogens, with excellent biocompatibility , real-time monitoring, and magnetically-targeting capacities. The multifunctional nanoparticles have great potential in antibacterial applications to inhibit the occurrence and progression of periodontitis .
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Qi Xu,Fang He,Zhimin Mo,Han Hu,Qianyuan He,Zushun Xu,Shengli Yang,Xiaojuan Qin
Emerging multimodal therapy strategies based on sonodynamic therapy (SDT) are foreseen as foundational in forthcoming tumor theranostics. Nevertheless, the therapeutic effects of SDT are limited by the hypoxic environment of the tumor microenvironment (TME). Based on this, nano-enzymes are envisioned to decompose excess hydrogen peroxide in the tumor microenvironment to generate oxygen. Here, PEG-PLGA-coated CeO 2 nanoparticles loaded with the sonosensitizer chlorin e6 (CC@PP) were prepared for cancer therapy based on a nanoprecipitation method. CC@PP possesses highly efficient catalase-like (CAT) properties, which are able to decompose overexpressed H 2 O 2 into O 2 and enhance the effect of O 2 -dependent sonodynamic therapy. In addition, it can act as a peroxidase (POD) at lower pH for chemodynamic therapy. Under the guidance of the US, CC@PP can perform synergistic sonodynamic and chemodynamic cancer therapy and inhibit tumor growth efficiently, CC@PP is biocompatible, has good in vivo fluorescence imaging effect, and has integrated diagnostic and therapeutic properties, which can be effectively aggregated at the tumor area. In this study, the effect of sonodynamic therapy was enhanced by improving the hypoxic environment in the TME, and multimodal synergistic enhancement of cancer therapy was realized.
研究领域:
肿瘤学
·
生物医学工程
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Houyang Hu,Xuechun Wang,Yilei Zhao,Jie Yan,Songyan Li,Chengzhilin Li,Xiaonan Zhao,Kanaparedu P. C. Sekhar,Ming Xia,Jianwei Jiao,Miaoqing Zhao,Guiqiang Zhang
Effective therapeutic approaches against head and neck squamous cell carcinoma (HNSCC), which is a prevalent malignant tumor, are currently lacking. Although immunotherapy has emerged as a promising strategy for treating HNSCC, its efficacy is severely limited by the immunosuppressive tumor microenvironment. Self-delivery nanoparticles, comprising Toll-like receptor (TLR) agonists and photosensitizers, were successfully developed to address this challenge in combinatorial immunotherapy for HNSCC treatment. After intravenous administration, these nanoparticles efficiently accumulated in tumors, enhancing the bioavailability of the agonist and triggering the TLR signaling pathway to remodel the immunosuppressive tumor microenvironment. Simultaneously, the photosensitizers induced immunogenic cell death and activated the stimulator of the interferon gene (STING) pathway in tumor cells via photodynamic therapy. The development of tumors was significantly inhibited by enhancing the antitumor immunity induced by the nanoparticles. This study provided a new paradigm for HNSCC immunotherapy, involving the synergistic regulation of the immune microenvironment with photodynamic therapy.
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
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Shuangyu Tian,Jinghang Li,Dongdong Wang,Yingchao Han,Honglian Dai,Lesan Yan
Sonodynamic therapy (SDT), an emerging cancer treatment with significant potential, offers the advantages of non-invasiveness and deep tissue penetrability. The method involves activating sonosensitizers with ultrasound to generate reactive oxygen species (ROS) capable of eradicating cancer cells, addressing the challenge faced by photodynamic therapy (PDT) where conventional light sources struggle to penetrate deep tissues, impacting treatment efficacy. This study addresses prevalent challenges in numerous nanodiagnostic and therapeutic agents, such as intricate synthesis, poor repeatability, low stability, and high cost, by introducing a streamlined one-step assembly method for nanoparticle preparation. Specifically, the sonosensitizer Chlorin e6 (Ce6) and the chemotherapy drug erlotinib are effortlessly combined and self-assembled under sonication, yielding carrier-free nanoparticles (EC-NPs) for non-small cell lung cancer (NSCLC) treatment. The resulting EC-NPs exhibit optimal drug loading capacity, a simplified preparation process, and robust stability both in vitro and in vivo, owing to their carrier-free characteristics. Under the synergistic treatment of sonodynamic therapy and chemotherapy, EC-NPs induce an excess of reactive oxygen in tumor tissue, prompting apoptosis of cancer cells and reducing their proliferative capacity. Both in vitro and in vivo experiments demonstrate superior therapeutic effects of EC-NPs under ultrasound conditions compared to free Ce6. In summary, our research findings highlight that the innovatively designed carrier-free sonosensitizer EC-NPs present a therapeutic option with commendable efficacy and minimal side effects.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Xukun Liao,Yong Cao,Wen Zhong,Dan Zheng,Lin Jin,Yongchao Yao,Chengli Yang
Photodynamic therapy (PDT) is a noninvasive therapeutic approach that is effective in killing primary tumors with minimal surgical trauma, but its usage in metastatic lesions of melanoma is restricted by spatial limitations. Recently, stimulator of interferon genes (STING) agoinst-mediated innate immunity can activate the STING pathway and further promote dendritic cell (DC) maturation, tumor-specific cytotoxic T lymphocyte, and natural killer cell infiltration and has emerged as a promising approach for cancer therapy. Herein, the authors intriduce facile nanoparticles named HTCS, which can co-deliver STING agonist (2′3′-cGAMP) and a mitochondrial targeting modified photosensitizer (TPP-PEI-Ce6). While HTCS were intravenously injected to mice, they were endocytosed into tumor cells through hyaluronic acid-mediated active targeting. Thereafter, TPP-PEI-Ce6 was delivered to mitochondria to generate a large variety of reactive oxygen species and killed tumor cells effectively. Then the tumor cell debris further gave rise to immunogenic cell death, which played a role in immunosuppression. Furthermore, 2′3′-cGAMP contained in cell debris activated the STING pathway to promote the release of inflammatory cytokines and the maturation of DCs. As a consequence, the HTCS could achieve photodynamic multiple immunotherapy for melanoma. This work demonstrates multifunctional nanoparticles that efficiently inhibit tumors by PDT and reversing their immunosuppression to realize a versatile therapeutic strategy.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 27
·11953-11962
·
IF 7.79
Xiaohan Qin,Mengzhu Zhang,Xu Hu,Qian Du,Zhipeng Zhao,Yue Jiang,Yuxia Luan
Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in the tumor microenvironment greatly compromise its therapeutic efficacy. To address the issues, here we designed a new Ce6 derivative (TCe6) by coupling Ce6 with amphiphilic D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), endowing Ce6 with an excellent amphiphilic feature. In particular, the overall reactive oxygen species (ROS) generation by TCe6 was significantly enhanced because TPGS could interact with mitochondrial complex II to induce extra ROS production, amplifying the total ROS production under PDT. Inspired by the unique property of α-cyano-4-hydroxycinnamate (CHC) in regulating lactate metabolism to spare more intracellular oxygen for PDT, TCe6 was further co-assembled with CHC to construct TCe6/CHC nanoparticles (NPs) for addressing the insufficient oxygen issue in PDT. The as-prepared TCe6/CHC NPs not only increased the efficiency of cell internalization but also improved the solubility and stability of Ce6 and CHC. Thanks to the extra ROS production by the TPGS unit, the amphiphilic feature of TCe6 and the CHC-mediated hypoxia microenvironment, the TCe6/CHC NPs demonstrated excellent PDT against tumor growth. This work provided a versatile strategy to solve the current bottleneck in photosensitizer-based PDT, holding great promise for the design of advanced photodynamic nanoplatforms.
研究领域:
纳米技术
·
药学
·
肿瘤学
✓ 已验证
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
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2022
·Vol. 33
·期 23
·235101
·
IF 3.953
Mengjia Yang,Xiaojun Lv,Siwen Zhan,Mengli Lu,Xueqiong Zhang,Tong Qiu
We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2 μM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Han Hu,Ruiqi Li,Piao Huang,Zhimin Mo,Qi Xu,Tao Hu,Shijie Yao,Xiaofang Dai,Zushun Xu
Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/ [email protected] , to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H 2 O 2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/ [email protected] nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 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）