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Hypoxia photodynamic therapy

Chao Zhang, Wei Feng, Elena Vodovozova, Daria Tretiakova, Ivan Boldyrevd, Yusha Li, Jurgen Kürths, Tingting Yu, Oxana Semyachkina-Glushkovskaya, Dan Zhu
The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1...
October 1, 2018: Biomedical Optics Express
Zhijuan Yang, Qian Chen, Jiawen Chen, Ziliang Dong, Rui Zhang, Jingjing Liu, Zhuang Liu
Despite the promises of applying nano-photosensitizers (nano-PSs) for photodynamic therapy (PDT) against cancer, severe tumor hypoxia and limited tumor penetration of nano-PSs would lead to nonoptimized therapeutic outcomes of PDT. Therefore, herein a biocompatible nano-PS is prepared by using tamoxifen (TAM), an anti-estrogen compound, to induce self-assembly of chlorin e6 (Ce6) modified human serum albumin (HSA). The formed HSA-Ce6/TAM nanocomplexes, which are stable under neutral pH with a diameter of ≈130 nm, would be dissociated into individual HSA-Ce6 and TAM molecules under the acidic tumor microenvironment, owing to the pH responsive transition of TAM from hydrophobic to hydrophilic...
October 11, 2018: Small
Qian Wang, Jia-Mi Li, Hui Yu, Kai Deng, Wei Zhou, Cai-Xia Wang, Yang Zhang, Kun-Heng Li, Ren-Xi Zhuo, Shi-Wen Huang
Photodynamic therapy (PDT) as an alternative choice of cancer treatment method has attracted increasing attention in the past few decades. A sufficient amount of oxygen is essential for the production of singlet oxygen (1O2) in successful PDT; however, hypoxia is a typical hallmark of cancer, which is one of the most important limitation factors of PDT. To overcome the hypoxic tumour microenvironment and achieve highly efficient photodynamic cancer therapy, herein, a photosensitizer Ce6-loaded fluorinated polymeric micelle (Ce6-PFOC-PEI-M) was constructed via the self-assembly of an amphiphilic polymer prepared from perfluorooctanoic acid and branched polyethyleneimine (10 kDa)...
October 11, 2018: Biomaterials Science
Niannian Li, Fei Xu, Jiejun Cheng, Ying Zhang, Gang Huang, Jun Zhu, Xi Shen, Dannong He
Amelioration of hypoxia is an important factor increasing the effects of anti-tumor therapies. In the present experiments, nanocapsules of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide (PFOB)/photosensitizers (IR780) have been developed to increase oxygen concentration inside the tumor and improve the outcome of photodynamic therapy (PDT). PFOB has high oxygen solubility, and IR780 is a photosensitizer particularly suited for a highly effective photodynamic therapy under the 808-nm laser irradiation...
December 1, 2018: Journal of Biomedical Nanotechnology
Yu Yang, Wenjun Zhu, Liangzhu Feng, Yu Chao, Xuan Yi, Ziliang Dong, Kai Yang, Weihong Tan, Zhuang Liu, Meiwan Chen
Photodynamic therapy (PDT) is a light-triggered therapy used to kill cancer cells by producing reactive oxygen species (ROS). Herein, a new kind of DNA nanostructure based on the coordination between calcium ions (Ca2+ ) and AS1411 DNA G quadruplexes to form nanoscale coordination polymers (NCPs) is developed via a simple method. Both chlorine e6 (Ce6), a photosensitizer, and hemin, an iron-containing porphyrin, can be inserted into the G-quadruplex structure in the obtained NCPs. With further polyethylene glycol (PEG) modification, we obtain Ca-AS1411/Ce6/hemin@pHis-PEG (CACH-PEG) NCP nanostructure that enables the intranuclear transport of photosensitizer Ce6 to generate ROS inside cell nuclei that are the most vulnerable to ROS...
October 10, 2018: Nano Letters
Ruyuan Song, Dehong Hu, Ho Yin Chung, Zonghai Sheng, Shuhuai Yao
Hypoxia in solid tumors may be a hindrance to effective treatments of tumors in achieving their therapeutic potential, especially for photodynamic therapy (PDT) which requires oxygen as the supplement substrate. Oxygen delivery using perfluorocarbon emulsions or lipid oxygen microbubbles has been developed as the agents to supply endogenous oxygen to fuel singlet oxygen generation in PDT. However, such methods suffer from premature oxygen release and storage issues. To address these limitations, we designed lipid-polymer bilaminar oxygen nanobubbles with chlorin e6 (Ce6) conjugated to the polymer shell as a novel oxygen self-supplement agent for PDT...
October 9, 2018: ACS Applied Materials & Interfaces
Yongyan Deng, Fan Jia, Shengyu Chen, Zhida Shen, Qiao Jin, Guosheng Fu, Jian Ji
A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively...
September 29, 2018: Biomaterials
S-Ja Tseng, Ivan M Kempson, Kuo-Yen Huang, Hsin-Jung Li, Yu-Chen Fa, Yi-Cheng Ho, Zi-Xian Liao, Pan-Chyr Yang
Solid tumors characteristically display higher levels of lactate production due to anaerobic metabolism of glucose. Meanwhile, the U.S. Food and Drug Administration (FDA) has approved virotherapy for use in cancer treatment; however systemic administration remains as a particular challenge. Here we report exploitation of tumor lactate production in designing a hypoxia-responsive carrier, self-assembled from hyaluronic acid (HA) conjugated with 6-(2-nitroimidazole)hexylamine, for localized release of recombinant adeno-associated virus serotype 2 (AAV2)...
October 5, 2018: ACS Nano
Yudi Ruan, Xiaodai Jia, Chao Wang, Wenyao Zhen, Xiue Jiang
Iron-manganese layered double hydroxide nanosheets were developed as an effective photothermal nanocarrier for loading a photosensitizer. The catalase-like activity enables the nanosheets to decompose H2 O2 into O2 , overcoming tumor hypoxia and enhancing O2 -dependent photodynamic therapy (PDT). The combination of PDT and photothermal therapy (PTT) can almost completely eliminate tumor tissues.
October 25, 2018: Chemical Communications: Chem Comm
Kai Zhang, Yuedong Zhang, Xiangdan Meng, Huiting Lu, Huan Chang, Haifeng Dong, Xueji Zhang
Hypoxia tumor microenvironment is a major challenge for photodynamical therapy (PDT), and hypoxia-activated chemotherapy combined PDT could be promising for enhanced anticancer therapy. In this study, we report an innovative 2-nitroimidazole derivative conjugated polyethylene glycol (PEG) amphoteric polymer theranostic liposome encapsulated a photosensitizer Chlorin e6 (Ce6), hypoxia-activated prodrug Tirapazamine (TPZ) and gene probe for synergistic photodynamic-chemotherapy. Ce6-mediated PDT upon irradiation with a laser induces hypoxia, which leads to the disassembly of the liposome and activates the antitumor activity of TPZ for improved cancer cell-killing...
December 2018: Biomaterials
Yanyan Liu, Yaqin Jiang, Meng Zhang, Zhongmin Tang, Mingyuan He, Wenbo Bu
The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is associated with a more malignant phenotype and poor survival in patients with tumors. The development of hypoxia modulation methods for advanced therapeutic activity is therefore of great interest but remains a considerable challenge. Since the significant development of nanotechnology and nanomedicine, functionalized nanomaterials can be exploited as adjuvant "drugs" for these oxygen-dependent standard therapies or as hypoxia initiators for advanced new therapies to solid tumors...
September 20, 2018: Accounts of Chemical Research
Huaqin Zuo, Junxian Tao, Hua Shi, Jian He, Zhengyang Zhou, Chao Zhang
W18 O49 -mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load W18 O49 nanoparticles (NPs) and metformin (PM-W18 O49 -Met NPs). Platelet membranes can protect W18 O49 from oxidation and immune evasion, and increase the accumulation of W18 O49 in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption...
September 15, 2018: Acta Biomaterialia
Shuang-Shuang Wan, Jin-Yue Zeng, Han Cheng, Xian-Zheng Zhang
This study reports a tumor-specific ROS-responsive nanoplatform capable of the combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic therapy (PDT). The nanoplatform is constructed on porous coordination network (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L-Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO for combined gas therapy...
December 2018: Biomaterials
Dehong Hu, Zhuwen Chen, Zonghai Sheng, Duyang Gao, Fei Yan, Teng Ma, Hairong Zheng, Mei Hong
Photodynamic therapy (PDT) is an alternative strategy for treating pancreatic cancer (PC) in clinics. However, the therapeutic efficacy is generally suppressed by inadequate oxygen supply in the hypoxic tumor microenvironment. Herein, hierarchical zeolite nanocarriers with hydrophilic mesoporous nanostructures and excellent biodegradability are synthesized via a one-pot wet chemical method. By co-loading with catalase and methylene blue (MB), a new type of oxygen self-sufficient PDT platform, a zeolite-catalase-MB nanocapsule (ZCM nanocapsule), is developed...
September 20, 2018: Nanoscale
Liang Zhang, Dong Wang, Ke Yang, Danli Sheng, Bin Tan, Zhigang Wang, Haitao Ran, Hengjing Yi, Yixin Zhong, Han Lin, Yu Chen
Phototherapy has emerged as a novel therapeutic modality for cancer treatment, but its low therapeutic efficacy severely hinders further extensive clinical translation and application. This study reports amplifying the phototherapeutic efficacy by constructing a near-infrared (NIR)-responsive multifunctional nanoplatform for synergistic cancer phototherapy by a single NIR irradiation, which can concurrently achieve mitochondria-targeting phototherapy, synergistic photothermal therapy (PTT)/photodynamic therapy (PDT), self-sufficient oxygen-augmented PDT, and multiple-imaging guidance/monitoring...
August 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Xin Luan, Ying-Yun Guan, Hai-Jun Liu, Qin Lu, Mei Zhao, Duxin Sun, Jonathan F Lovell, Peng Sun, Hong-Zhuan Chen, Chao Fang
Vascular-targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)-based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxia-activated prodrug (HAP), and HIF-1α siRNA (siHIF-1α) (3) is reported...
August 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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...
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...
October 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.
August 14, 2018: Chemical Communications: Chem Comm
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