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Hypoxia photodynamic therapy

Yanjing Li, Hong Sui, Cailing Jiang, Shumin Li, Yu Han, Peng Huang, Xiaoxue Du, Jingwen Du, Yuxian Bai
BACKGROUND/AIMS: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. METHODS: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene...
August 10, 2018: Cellular Physiology and Biochemistry
Hairong Wang, Yu Chao, Jingjing Liu, Wenwen Zhu, Guanglin Wang, Ligeng Xu, Zhuang Liu
Tumor hypoxia is known to be one of critical factors that aggravate the tumor resistance to photodynamic therapy (PDT) in which oxygen is essential for tumor destruction. Herein, catalase, an enzyme to trigger hydrogen peroxide (H2 O2 ) decomposition, is modified by in-situ free radical polymerization, using meso-tetra(p-hydroxyphenyl) porphine (THPP) as the cross-linker to enable condensed grafting of short polyethylene glycol (PEG) chains on the protein surface as a permeable brush-like safeguard. The formulated catalase-entrapped nanocapsules (CAT-THPP-PEG) with enhanced enzyme stability can be labeled with 99m Tc4+ , a radioisotope ion that is chelated by the porphyrin structure of THPP, to allow in vivo single-photon emission computed tomography (SPECT) imaging...
August 4, 2018: Biomaterials
Wen Jiang, Ian Michael Delahunty, Jin Xie
Hypoxia is behind tumor resistance in both chemotherapy and photodynamic therapy. This editorial highlights a study by Cai et al. [12] that a hemoglobin and human serum albumin hybrid protein nanoparticle can simultaneously deliver O2 , chemotherapeutics, and photosensitizers to tumors for enhanced chemophototherapy.
2018: Theranostics
Jian Sun, Xiao Li, Ke Du, Fude Feng
We designed a water soluble benzotriazole-cored donor-acceptor-donor molecule bearing four triphenylphosphonium moieties for mitochondria targeting. The organic molecule showed strong singlet oxygen sensitizing capability (ΦΔ 0.64), minimal dark cytotoxicity and high photocytotoxicity. The molecule is efficient in photodynamic killing of tumour cells under normal and hypoxia conditions using a very low light flux, and has potential in near-infrared two-photon imaging and photodynamic therapy.
July 31, 2018: Chemical Communications: Chem Comm
Zhenyu Luo, Hao Tian, Lanlan Liu, Zhikuan Chen, Ruijing Liang, Ze Chen, Zhihao Wu, Aiqing Ma, Mingbin Zheng, Lintao Cai
Hypoxia is a characteristic feature of solid tumors and an important causation of resistance to chemotherapy and photodynamic therapy (PDT). It is challenging to develop efficient functional nanomaterials for tumor oxygenation and therapeutic applications. Methods: Through disulfide reconfiguration to hybridize hemoglobin and albumin, tumor-targeted hybrid protein oxygen carriers (HPOCs) were fabricated, serving as nanomedicines for precise tumor oxygenation and simultaneous enhancement of hypoxia-dampened chemotherapy and photodynamic therapy...
2018: Theranostics
Lian-Hua Fu, Chao Qi, Jing Lin, Peng Huang
Glucose oxidase (GOx) is an endogenous oxido-reductase that is widely distributed in living organisms. Over recent years, GOx has attracted increasing interest in the biomedical field due to its inherent biocompatibility, non-toxicity, and unique catalysis against β-d-glucose. GOx efficiently catalyzes the oxidization of glucose into gluconic acid and hydrogen peroxide (H2O2), which can be employed by various biosensors for the detection of cancer biomarkers. Various cancer therapeutic strategies have also been developed based on the catalytic chemistry of GOx: (1) the consumption of glucose provides an alternative strategy for cancer-starvation therapy; (2) the consumption of oxygen increases tumor hypoxia, which can be harnessed for hypoxia-activated therapy; (3) the generation of gluconic acid enhances the acidity of the tumor microenvironment, which can trigger pH-responsive drug release; (4) the generation of H2O2 increases the levels of tumor oxidative stress, and the H2O2 can be converted into toxic hydroxyl radicals that can kill cancer cells upon exposure to light irradiation or via the Fenton reaction...
July 19, 2018: Chemical Society Reviews
Aleksandra Kawczyk-Krupka, Wojciech Latos, Piotr Oleś, Zenon P Czuba, Magdalena Latos, Magdalena Krupka, Huang Pengyun, Chuanshan Xu, Grzegorz Cieślar, Aleksander Sieroń
Photodynamic therapy (PDT) becomes a method of personalized cancer treatment, based on the individual determination of cancer biomarkers. The aim of the study was to evaluate the influence of PDT with δ-aminolevulinic acid (ALA-PDT) used in sub-lethal dose on the interleukins secretion (IL-6, IL-8 and IL-10) by the residual colon cancer cells (CCC) under hypoxia-like conditions (addition of cobalt chloride- CoCl2 ). CCC: SW480 and SW620 cells were incubated with ALA, CoCl2 and irradiated with red light. The cells viability was detected using MTT assay, LDH and apoptosis tests...
July 14, 2018: Photodiagnosis and Photodynamic Therapy
Wen-Long Liu, Tao Liu, Mei-Zhen Zou, Wu-Yang Yu, Chu-Xin Li, Zu-Yang He, Ming-Kang Zhang, Miao-Deng Liu, Zi-Hao Li, Jun Feng, Xian-Zheng Zhang
Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in mammals, an aggressive man-made RBC (AmmRBC) is created to combat the hypoxia-mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme-mimicking polydopamine, and polydopamine-carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes...
July 17, 2018: Advanced Materials
Zhikuan Chen, Lanlan Liu, Ruijing Liang, Zhenyu Luo, Huamei He, Zhihao Wu, Hao Tian, Mingbin Zheng, Yifan Ma, Lintao Cai
An ideal cancer therapeutic strategy is expected to possess potent ability to not only ablate primary tumors but also prevent distance metastasis and relapse. In this study, human serum albumin was hybridized with hemoglobin by intermolecular disulfide bonds to develop a hybrid protein oxygen nanocarrier with chlorine e6 encapsulated (C@HPOC) for oxygen self-sufficient photodynamic therapy (PDT). C@HPOC realized the tumor-targeted co-delivery of photosensitizer and oxygen, which remarkably relieved tumor hypoxia...
July 19, 2018: ACS Nano
Ming Liu, Lei Wang, Xiaohua Zheng, Shi Liu, Zhigang Xie
The oxygen-dependent feature of most photosensitizers (PSs) and the aggravated hypoxia tumor microenvironment seriously impede the photodynamic therapy (PDT) effectiveness. However, this undesirable impediment can be utilized to further trigger the activation of hypoxia-sensitive prodrugs. Moreover, a combined therapy can be used by associating PDT with hypoxia-activated chemotherapy. Herein, a multifunctional Hf-porphyrin nanoscale metal-organic framework (NMOF) platform [Hf/tetra(4-carboxyphenyl)porphine (TCPP)] has been synthesized, with a high porphyrin loading capacity and a well-ordered coordination array preventing porphyrin self-quenching, thus greatly improving the generation efficiency of reactive oxygen species (ROS), which is helpful for PDT...
July 25, 2018: ACS Applied Materials & Interfaces
Shutao Gao, Pengli Zheng, Zhenhua Li, Xiaochen Feng, Weixiao Yan, Shizhu Chen, Weisheng Guo, Dandan Liu, Xinjian Yang, Shuxiang Wang, Xing-Jie Liang, Jinchao Zhang
Improving the supply of O2 and the circulation lifetime of photosensitizers for photodynamic therapy (PDT) in vivo would be a promising approach to eliminate hypoxic tumors. Herein, by taking advantage of the significant gas-adsorption capability of metal-organic frameworks (MOFs), a biomimetic O2 -evolving photodynamic therapy (PDT) nanoplatform with long circulating properties was fabricated. Zirconium (IV)-based MOF (UiO-66) was used as a vehicle for O2 storing, then conjugated with indocyanine green (ICG) by coordination reaction, and further coated with red blood cell (RBC) membranes...
September 2018: Biomaterials
Yu Han, Zhongping Chen, Hong Zhao, Zengshi Zha, Wendong Ke, Yuheng Wang, Zhishen Ge
Tumor hypoxia strikingly restricts photodynamic therapy (PDT) efficacy and limits its clinical applications in cancer therapy. The ideal strategy to address this issue is to develop oxygen-independent PDT systems. Herein, the rationally designed tumor pH-responsive polymeric micelles are devised to realize oxygen-independent combined PDT and photothermal therapy (PTT) under near-infrared light (NIR) irradiation. The triblock copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-(piperidin-1-yl)ethyl methacrylate) (PEG-b-PCL-b- PPEMA), was prepared to co-encapsulate cypate and singlet oxygen donor (diphenylanthracene endoperoxide, DPAE) via self-assembly to obtain the micellar delivery system (C/O@N-Micelle)...
August 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ruijing Liang, Lanlan Liu, Huamei He, Zhikuan Chen, Zhiqun Han, Zhenyu Luo, Zhihao Wu, Mingbin Zheng, Yifan Ma, Lintao Cai
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO2 , AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC...
September 2018: Biomaterials
Xiaolong Zhang, Ming Wu, Jiong Li, Shanyou Lan, Yongyi Zeng, Xiaolong Liu, Jingfeng Liu
The tumor hypoxic environment as well as photodynamic therapy (PDT)-induced hypoxia could severely limit the therapeutic efficacy of traditional PDT. Fortunately, the smart integration of hypoxia-responsive drug delivery system with PDT might be a promising strategy to enhance the PDT efficiency that is hindered by the hypoxic environment. Herein, a novel azobenzene (AZO) containing conjugated polymers (CPs)-based nanocarriers (CPs-CPT-Ce6 NPs) was constructed for the combination of PDT with chemotherapy, as well as to enhance the hypoxia-responsive drug release by light...
July 5, 2018: ACS Applied Materials & Interfaces
Jingqiu Li, Jinzhao Huang, Yanxiao Ao, Shiyu Li, Yu Miao, Zhongzheng Yu, Lingtao Zhu, Xiaoli Lan, Yanhong Zhu, Yan Zhang, Xiangliang Yang
Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy...
July 11, 2018: ACS Applied Materials & Interfaces
Zhen Lu Yang, Wei Tian, Qing Wang, Ying Zhao, Yun Lei Zhang, Ying Tian, Yu Xia Tang, Shou Ju Wang, Ying Liu, Qian Qian Ni, Guang Ming Lu, Zhao Gang Teng, Long Jiang Zhang
Oxygen (O2 ) plays a critical role during photodynamic therapy (PDT), however, hypoxia is quite common in most solid tumors, which limits the PDT efficacy and promotes the tumor aggression. Here, a safe and multifunctional oxygen-evolving nanoplatform is costructured to overcome this problem. It is composed of a prussian blue (PB) core and chlorin e6 (Ce6) anchored periodic mesoporous organosilica (PMO) shell (denoted as PB@PMO-Ce6). In the highly integrated nanoplatform, the PB with catalase-like activity can catalyze hydrogen peroxide to generate O2 , and the Ce6 transform the O2 to generate more reactive oxygen species (ROS) upon laser irradiation for PDT...
May 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Xingshu Li, Nahyun Kwon, Tian Guo, Zhuang Liu, Juyoung Yoon
Despite its clinical promise, photodynamic therapy (PDT) suffers from a key drawback associated with its oxygen-dependent nature, which limits its effective use against hypoxic tumor. Moreover, both PDT-mediated oxygen consumption and microvascular damage further increase tumor hypoxia and, thus, impede therapeutic outcomes. In recent years, numerous investigations have focused on strategies for overcoming this drawback of PDT. These efforts, which are summarized in this review, have produced many innovative methods to avoid limits of PDT associated with hypoxia...
May 29, 2018: Angewandte Chemie
Shuting Xu, Xinyuan Zhu, Chuan Zhang, Wei Huang, Yongfeng Zhou, Deyue Yan
Cancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy. Here, we hypothesize that an oxygen and Pt(II) self-generating multifunctional nanocomposite could reverse the hypoxia-triggered PDT resistance. The nanocomposite contains Pt(IV) and chlorin e6, in which upconversion nanoparticles are loaded to convert 980 nm near-infrared light into 365 nm and 660 nm emissions. Upon accumulation at the tumor site, a 980 nm laser is used to trigger the nanocomposite to generate O2 for consumption in the PDT process and to produce cytotoxic reactive oxygen species...
May 24, 2018: Nature Communications
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...
June 13, 2018: ACS Applied Materials & Interfaces
Zhuang Lv, Liang Zou, Huanjie Wei, Shujuan Liu, Wei Huang, Qiang Zhao
It is very meaningful to develop bifunctional therapeutic agents which can monitor the tumor hypoxia in real time as well as maintain good photodynamic therapy (PDT) effect under hypoxia. To achieve it, herein, a series of hydrophilic phosphorescent starburst Pt(II) porphyrins as bifunctional therapeutic agents for simultaneous tumor hypoxia imaging and highly efficient PDT have been rationally designed and synthesized. They have been obtained by using Pt(II) porphyrins as the functional core and cationic oligofluorenes as the arms...
June 13, 2018: ACS Applied Materials & Interfaces
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