Nature Communications
·
2022
·Vol. 13
·期 1
·1-10
·
IF 17.694
An Jing,Tang Shanliang,Hong Gaobo,Chen Wenlong,Chen Miaomiao,Song Jitao,Li Zhiliang,Peng Xiaojun,Song Fengling,Zheng Wen-Heng
The most common working mechanism of photodynamic therapy is based on high-toxicity singlet oxygen, which is called Type II photodynamic therapy. But it is highly dependent on oxygen consumption. Recently, Type I photodynamic therapy has been found to have better hypoxia tolerance to ease this restriction. However, few strategies are available on the design of Type I photosensitizers. We herein report an unexpected strategy to alleviate the limitation of traditional photodynamic therapy by biotinylation of three photosensitizers (two fluorescein-based photosensitizers and the commercially available Protoporphyrin). The three biotiylated photosensitizers named as compound 1 , 2 and 3 , exhibit impressive ability in generating both superoxide anion radicals and singlet oxygen. Moreover, compound 1 can be activated upon low-power white light irradiation with stronger ability of anion radicals generation than the other two. The excellent combinational Type I / Type II photodynamic therapy performance has been demonstrated with the photosensitizers 1 . This work presents a universal protocol to provide tumor-targeting ability and enhance or trigger the generation of anion radicals by biotinylation of Type II photosensitizers against tumor hypoxia.
研究领域:
肿瘤学
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药物化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Non-coding RNA Research
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2025
·
IF 4.7
Ying Wen,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80%. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after PDT. Inhibition of MALAT1 increased PDT-induced ROS, which promoted the apoptosis. Pearson correlation analysis confirmed that there was a positive correlation between MALAT1 and HO-1, and MALAT1 inhibition down-regulated HO-1, whereas concomitant overexpression of HO-1 was able to eliminate the PDT-induced ROS and inhibit apoptosis. The direct binding of MALAT1 to Kelch-like ECH-associated protein 1 (Keap1) protein was confirmed by high-throughput sequencing, RNA pulldown, silver staining and western blotting assays. Si-Keap1 was able to rescue the down-regulation of HO-1 caused by MALAT1 inhibition, restoring the elimination of ROS by HO-1 and attenuating the effect of PDT. In addition, PDT effectively reduced parathyroid hormone (PTH) secretion in SHPT rats, and this effect was further enhanced in combination with MALAT1 inhibitors. Overall, MALAT1 activates downstream HO-1 expression by binding to Keap1, thereby reducing ROS and inhibiting apoptosis, which in turn mediates PDT resistance in SHPT. Inhibition of MALAT1 significantly enhanced the efficacy of PDT, suggesting a potential therapeutic target for improving PDT for SHPT outcomes.
研究领域:
医学
·
分子生物学
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DOI
PubMed
高影响因子
RSC Advances
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2022
·Vol. 12
·期 16
·10005-10013
·
IF 4.036
Xiaofeng Meng,Jingwei Guan,Shanshan Lai,Liming Fang,Jianyu Su
Antimicrobial photodynamic therapy (aPDT) is a highly attractive therapy due to its advantages of being a non-antibiotic procedure for reducing drug-resistant microbes. Curcumin (CCM) has been considered as a natural photosensitizer for PDT with prominent antibacterial, antifungal, and anti-proliferative activity. However, its excellent biological and pharmacological activities are limited because of its low solubility, rapid metabolization and instability. Herein, we reported a promising agent based on CCM-incorporated into zeolitic imidazolate framework-8 (ZIF@CCM). The as-prepared nanoparticle exhibited high drug loading capability (11.57%) and drug loading encapsulation (82.76%). Additionally, ZIF@CCM displayed a pH-responsive drug release behavior and chemophotodynamic therapy for excellent antibacterial activity. The underlying mechanism elucidated that Zn2+ released from ZIF-8 increased the permeability of the bacterial cell membrane with leakages of K+. The overproduction of extracellular ROS further resulted in the disrupted bacterial cell membrane and distorted bacterial morphology. Thus, ZIF@CCM-mediated photodynamic activation might be a promising treatment strategy for microbial inactivation.
研究领域:
药学
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纳米技术
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生物医学工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2021
·
IF 14.593
Meiqi Chang,Wei Feng,Li Ding,Hongguang Zhang,Caihong Dong,Yu Chen,Jianlin Shi
Tumor oxygenation level has been regarded as an attractive target to elevate the efficiency of photodynamic therapy (PDT). Cyanobacterial photosynthesis-mediated reversal of tumor hypoxia could enable an oxygen-boosted PDT, but is limited by scant penetration depth and efficiency of external light. Herein, aiming at the dual purposes of reducing biological toxicity induced by long-term light irradiation and alleviating hypoxia, we here introduce a novel-designed CaAl 2 O 4 :Eu,Nd blue persistent luminescence material (PLM) as the in vivo light source after pre-excited in vitro . The ingenious construction of blue-emitting PLM with “optical battery” characteristics activates cyanobacterial cells and verteporfin simultaneously, which performs the successive oxygen supply and singlet oxygen generation without the long-term external excitation, resulting in the modulated tumor hypoxic microenvironment and enhanced photodynamic tumor proliferation inhibition efficiency. Both in vitro cellular assessment and in vivo tumor evaluation results affirm the advantages of self-produced oxygen PDT system and evidence the notable antineoplastic outcome. This work develops an irradiation-free photosynthetic bacteria-based PDT platform for the optimization of both oxygen production capacity and light utilization efficiency in cancer treatment, which is expected to promote the clinical progress of microbial-based photonic therapy.
研究领域:
癌症治疗
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生物光子学
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材料科学
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生物工程
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产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
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2021
·
IF 6.707
Shengyu Zhou,Xiaodan Jiao,Ying Jiang,Yanan Zhao,Peng Xue,Yingshuai Liu,Jing Liu
Two-dimensional MoS 2 (2D-MoS 2 ) and its nanocomposites have been extensively studied in cancer therapy research since their prominent surface area and NIR absorption ability. In this work, Eu 3+ -incorporated MoS 2 (MoS 2 :Eu 3+ ) nanoflowers with enhanced photothermal conversion efficiency (PCE) were successfully developed by a one-step bottom-up hydrothermal method. Under 808 nm near-infrared (NIR) laser irradiation, the photothermal agents MoS 2 :5%Eu 3+ nanoflowers have a PCE at ~ 49.05%, which is 1.75 times higher than the pristine MoS 2 . MoS 2 :5%Eu 3+ as efficient photosensitizers also promote generation of cytotoxic reactive oxygen species (ROS) under 808 nm laser irradiation, thus achieving photodynamic therapy (PDT) for cancers at the same time. Enhanced in vitro breast cancer therapy through the combination of photothermal therapy (PTT) and PDT is clearly proved by using the MoS 2 :Eu 3+ nanosheet as a multifunctional nanoprobe. The unique MoS 2 :Eu 3+ works as a promising nanoprobe for PDT/PTT cancer therapies, and also provides a novel strategy for PCE improvement of the 2D-MoS 2 .
研究领域:
纳米医学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Qi Zong,Guozhen Wang,Zijie Zhao,Wenzhuo Li,Xiaonan Hou,Mengfei Yao,Duo Tang,Chao Sheng,Zijia Liu,Yuchen Zheng,Zhixiang Zhou,Xiaofei Zhang,Xiao Li
Hypocrellin A (HA) is an efficient photosensitizer for photodynamic therapy in recent years. In order to improve the delivery of this photosensitizer, dissolving HA microneedles were established. Firstly, dissolving microneedles were prepared from HA by a two-step solvent casting method. Then, the dissolving HA microneedle were characterized by stereomicroscope, laser confocal microscope, scanning electron microscope, differential scanning calorimeter (DSC), X-ray diffractometer (XRD) and fourier infrared spectrometer (FTIR). Finally, the transdermal cumulative penetration experiments were conducted. The results showed that the dissolving HA microneedle has a conical shape with an average height of 650 μm. The mechanical strength endure a force of 44.78 N, resulting in 0.20 N per needle. The in vitro transdermal experiment showed that the dissolving HA microneedle almost completely dissolved in 5 minutes after insertion into the mouse skin. The depth of drug penetration through the skin can reach 601.36 μm. Moreover, the dissolving HA microneedle significantly improved the cumulative transdermal penetration efficiency of the photosensitizer through the skin. Therefore, the present study successfully established a dissolving microneedle of HA, which can quickly dissolve and significantly improve the transdermal delivery efficiency of HA.
研究领域:
药剂学
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生物医学工程
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产品关联
DOI
高影响因子
Theranostics
·
2016
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IF 8.854
Caixia Yue,Yuming Yang,Chunlei Zhang,Gabriel Alfranca,Shangli Cheng,Lijun Ma,Yanlei Liu,Xiao Zhi,Jian Ni,Weihua Jiang,Jie Song,Jesús M. de la Fuente,Daxiang Cui
Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for cancer. Here we report, for the first time, synthesis of a new mitochondria-targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel compound, polyethylene glycol was functionalized with thioketal linker-modified camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL-CPT-PEG 1K -TPP. The ZnPc/CPT-TPPNPs was constructed for delivery of the photosensitizer Zinc phthalocyanine (ZnPc) by blending the block copolymer TL-CPT-PEG 1K -TPP with 1, 2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG).Triphenylphosphine can accumulate selectively several hundred-fold within mitochondria. The thioketal linker is ROS-responsive and CPT can be released upon ROS cleavage. We also show that the ZnPc loaded in ZnPc/CPT-TPPNPs absorbed the 633 nm laser to produce ROS, which could be utilized both in photodynamic therapy and to cleave the thioketal linker thereby releasing camptothecin for chemotherapy. Thus, the mitochondria-targeting nanoparticles could elevate photodynamic therapeutic efficacy. Our results showed that surface modification of the nanoparticles with triphenylphosphine cations facilitated efficient subcellular delivery of the photosensitizer to mitochondria. The nanoparticles had a good ROS-responsive effect to release CPT, which could transfer to the nucleus and interfere with DNA replication as a topoisomeraseⅠinhibitor. Thus, the blended nanoparticles provide a new promising approach as a mitochondria-targeting ROS-activated chemo- and photodynamic therapy with a single light source for lung cancer.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
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2025
·
IF 6
Zhiling Chen,Rui Zhang,Tao Wang,Yanan Peng,Qionglin Zhou,Peipei Cao,Xinxin Xiao,Fengling Li,Ziming Wei,Yuanyuan Wang,Dan Xu,Bin Qiao,Shaowen Cheng,Qiang Wu,Lina Niu
Bacterial infections present a significant threat to human health, a challenge that is intensified by the slow pace of novel antibiotic development and the swift emergence of bacterial resistance. The development of novel antibacterial agents is crucial. Indocyanine green (ICG), a widely used imaging dye, efficiently generates reactive oxygen species (ROS) and heat for treating bacterial infections but suffers from aggregation and instability, limiting its efficacy. In this study, tungsten disulfide (WS₂) nanosheet with a high surface area was used to load ICG, creating a multifunctional nanocomposite, WS 2 /ICG, aimed at treating bacteria-infected wounds. The two-dimensional surface structure of WS₂ provides dispersible binding sites for ICG, and the synthesized nanocomposite exhibits excellent stability. Under near-infrared (NIR) laser excitation, the generated heat further synergistically enhances the yield of singlet oxygen. Additionally, the WS₂/ICG nanoplatform synergistically combines photothermal effect with photodynamic effect, achieving a “1 + 1 > 2” enhancement. Upon NIR laser excitation, the nanocomposite disrupts bacterial cell membranes through localized heating and ROS accumulation, leading to energy metabolism system disruption and subsequent bacterial lysis and death. The findings demonstrate WS₂/ICG's outstanding antibacterial properties and biocompatibility, effectively treating skin infections and promoting tissue regeneration, providing a simple and promising solution for bacteria-infected wounds.
研究领域:
生物医学工程
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纳米医学
·
感染与免疫
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产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2024
·
IF 6.1
Bo-Mei Liu,Yue Lin,Yingchun Liu,Shanqing Zhang,Jing Wang,Hui Zhang,Jesse Zhu
Ultraviolet (UV) emitting persistent luminescence (PersL) materials have aroused significant interest, owing to their unique self-illuminating high-photo-energy feature under excitation-free conditions. In particular, the advent of X-rays as a charging source for UV PersL has facilitated the control of PersL properties and triggered a breakthrough in possible applications such as X-ray imaging techniques, phototherapy, photocatalysis, and optical information storage. Here, we present novel PersL materials that exhibit ultra-long UV emission for over 2000 h, as detected with a spectrometer. Experimental characterization revealed that the intrinsic oxygen vacancies associated with the local structure of the perovskite LaGaO3 can function as traps, which have super capabilities in energy collection and storage triggered by X-ray irradiation. Notably, this design concept is guided by utilizing an oxygen-defect perovskite as a host, which can serve as powerful guidance for expediting the discovery of new PersL materials. Moreover, due to excellent UV PersL performances, the proposed photodynamic therapy (PDT) platform LaGaO3:Bi,Sb@g-C3N4 demonstrates excellent PDT efficiency in vivo using low-dose X-ray irradiation. Our discovery of this UV PersL material is expected to provide directional solutions and novel perspectives for the development and application of UV luminescence technology.
研究领域:
材料科学
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医学
·
光学工程
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Hui Zhang,Ronghua Shi,Anjian Xie,Juchuan Li,Long Chen,Ping Chen,Shikuo Li,Fangzhi Huang,Yuhua Shen
A novel inorganic/organic hybrid hydrogel system containing titanium dioxide (TiO2)/poly(ethylene glycol) double acrylates (PEGDA) was prepared by in situ photopolymerization on tumor cells for photodynamic therapy (PDT). TiO2 nanorods with diameter of ∼5 nm and length of ∼25 nm in this system presented dual functions, as effective photosensitizers for PDT and initiators for causing the in situ formation of hydrogel, under near-infrared (NIR) irradiation. The hybrid hydrogel retained the TiO2 around tumor cell to form a drug-loaded hydrogel shell. This resulted in a high concentration of singlet oxygen (1O2) under NIR irradiation, which induced apoptosis of tumor cell. Also, the hydrogel could reduce the side effects by preventing TiO2 from migrating to normal tissue. Furthermore, the TiO2 nanorods in this hydrogel shell were photochemically recyclable and could be reused in regular treatment. The outcomes of this study provide a new way to exploit multifunction of inorganic semiconductor nanomaterials for a variety of biomedical applications.
研究领域:
生物医学工程
·
纳米医学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xuechun Wang,Jie Yan,Yilei Zhao,Songyan Li,Zilin Ma,Xiuying Duan,Yuelan Wang,Jianwei Jiao,Changping Gu,Guiqiang Zhang
Proteolysis targeting chimera (PROTAC) has recently emerged as a promising strategy to selectively degrade target proteins in the treatment of various diseases. However, it has low bioavailability due to strong hydrophobicity, poor membrane permeability, and nonspecific distribution in vivo, which greatly limits its application. In this study, self-delivery PROTAC nanoparticles (designated as CP NPs) integrating gefitinib-based PROTACs and photosensitizers were developed to efficiently degrade mutated epidermal growth factor receptor (EGFR), a crucial kinase for cell growth and survival, while simultaneously triggering photodynamic therapy and immunotherapy. The prepared NPs enhanced the tumor accumulation of PROTACs, which led to the selective degradation of EGFR mutations and a reduction in programmed cell death protein ligand 1 levels, thereby alleviating tumor immunosuppression and immune tolerance. Moreover, under laser irradiation, the coloaded photosensitizers triggered potent photodynamic therapy effects and induced immunogenic cell death, which worked synergistically with PROTACs toward eliciting a robust antitumor immune response. In a mouse model of lung cancer, primary, distant, and lung metastatic tumors were significantly suppressed. This work highlights the potential of nano-PROTACs for degrading target proteins and facilitating combination photodynamic immunotherapy toward expanding PROTAC applications in cancer therapy.
研究领域:
肿瘤学
·
药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Tianyu Zhu,Jipeng Ding,Fan Zheng,Yanpeng Fang,Wenzhi Huang,Ying Yin,Wenbin Zeng
Nitrogen mustard, a widely used chemotherapeutic agent for more than 70 years, exhibits significant efficacy. However, its clinical applications are severely limited by poor tumor selectivity and severe side effects on normal tissues. To address these limitations, we developed a near-infrared (NIR)-activatable nitrogen mustard prodrug, MBNM. Upon NIR irradiation, the controlled cleavage of the urea bond within MBNM facilitates the simultaneous release of nitrogen mustard and methylene blue (MB), enabling a synergistic approach combining chemotherapy and photodynamic therapy (PDT) for effective tumor suppression. Moreover, the release of MB upon activation enables real-time monitoring of prodrug activation. Notably, MBNM demonstrated significantly improved biosafety compared to free nitrogen mustard. These findings suggest that the photocleavable prodrug MBNM offers a promising strategy for safe and effective combination cancer therapy.
研究领域:
肿瘤学
·
药理学
✓ 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）