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Hypoxia photodynamic therapy

Tuanwei Li, Lifeng Yan
Photodynamic therapy (PDT) is an appealing therapeutic modality in management of some solid tumors and other diseases for its minimal invasion and non-systemic toxicity. However, the hydrophobicity and non-selectivity of the photosensitizers, inherent serious hypoxia of tumor tissues and limited penetration depth of light restrict PDT further applications in clinic. Functional polymer nanoparticles can be used as a nanocarrier for accurate PDT. Here, we elucidate the mechanism and application of PDT in cancer treatments, and then review some strategies to administer the biodistribution and activation of photosensitizers (PSs) to ameliorate or utilize the tumor hypoxic microenvironment to enhance the photodynamic therapy effect...
November 30, 2018: Pharmaceuticals
Xiaoli Cai, Yanan Luo, Yang Song, Dong Liu, Hongye Yan, He Li, Dan Du, Chengzhou Zhu, Yuehe Lin
Despite great progress in photodynamic therapy (PDT), the therapeutic effect is still limited by some points, such as tumor hypoxia, the short lifetime and the limited action region of 1O2. Herein, a special kind of three-dimensional dendritic mesoporous silica nanosphere (3D-dendritic MSN) was synthesized and used as a robust nanocarrier to deliver abundant hydrophobic photosensitizer chlorin e6 (Ce6) to the A549 lung cancer cells. To address the tumor hypoxia issue, the nanozyme Pt nanoparticles (Pt NPs) were immobilized onto the channels of 3D-dendritic MSNs to catalyze the conversion of intracellular H2O2 to oxygen...
November 30, 2018: Nanoscale
Jian Deng, Fang Liu, Lina Wang, Yang An, Min Gao, Zheng Wang, Yanjun Zhao
Triggered drug release from anti-tumor nanomedicine is an efficient approach to address the dilemma of systemic nanocarrier stability and on-demand drug liberation in tumor sites. Combinational drug delivery has been a useful means to enhance antitumor efficacy and reduce adverse effects. We report a multifunctional micelle for dually hypoxia- and singlet oxygen-responsive integration of chemotherapy and photodynamic therapy. The micelles were made of a nitroimidazole (NI)-bearing polymer; doxorubicin (Dox) and chlorin e6 (Ce6) were selected as the model chemodrug and photosensitizer, respectively...
November 30, 2018: Biomaterials Science
Jingjing Liu, Longlong Tian, Rui Zhang, Ziliang Dong, Hairong Wang, Zhuang Liu
The abundant tumor extracellular matrix (ECM) could result in the insufficient tumor retention and ineffective intra-tumor penetration of therapeutic agents, as well as acidic & hypoxic tumor microenvironment (TME), further leading to the unsatisfactory therapeutic outcomes for many types of therapies. Therefore, developing strategies to modulate the TME by selectively degrading the condensed ECM may be helpful to improve existing cancer therapies. Herein, collagenase (CLG) encapsulated nanoscale coordination polymers (NCPs) are synthesized based on Mn2+ and an acid-sensitive benzoic-imine organic linker, and then modified by polyethylene glycol (PEG)...
November 23, 2018: ACS Applied Materials & Interfaces
Silvia Alonso-de Castro, Alessio Terenzi, Sonja Hager, Bernhard Englinger, Adriana Faraone, Javier Calvo Martínez, Markus Galanski, Bernhard K Keppler, Walter Berger, Luca Salassa
We have recently demonstrated that riboflavin (Rf) functions as unconventional bioorthogonal photocatalyst for the activation of PtIV prodrugs. In this study, we show how the combination of light and Rf with two PtIV prodrugs is a feasible strategy for light-mediated pancreatic cancer cell death induction. In Capan-1 cells, which have high tolerance against photodynamic therapy, Rf-mediated activation of the cisplatin and carboplatin prodrugs cis,cis,trans-[Pt(NH3 )2 (Cl)2 (O2 CCH2 CH2 CO2 H)2 ] (1) and cis,cis,trans-[Pt(NH3 )2 (CBDCA)(O2 CCH2 CH2 CO2 H)2 ] (2, where CBDCA = cyclobutane dicarboxylate) resulted in pronounced reduction of the cell viability, including under hypoxia conditions...
November 21, 2018: Scientific Reports
Jintong Liu, Ping Du, Tianrui Liu, Bernardino J Córdova Wong, Weiping Wang, Huangxian Ju, Jianping Lei
Selecting the timing of laser treatment is an important task for improving O2 -dependent photodynamic therapy (PDT) efficiency. Here, a black phosphorus-based strategy was developed for dual-mode monitoring oxygen self-supply, enhancing photodynamic therapy, and feeding back therapeutic effect. The hybridized nanoplatform (R-MnO2 -FBP) was prepared by assembly of Rhodamine B (RhB)-encapsulated manganese dioxide (R-MnO2 ) as O2 supplier and indicator, and fluorescein isothiocyanate (FITC)-labelled peptide-functionalized black phosphorus as the theranostic agent...
October 17, 2018: Biomaterials
Zhongbao Li, Min Wu, Hongzhen Bai, Xingang Liu, Guping Tang
Herein, we report a light-enhanced hypoxia-responsive nanoparticle for synergic treatment of solid tumors. The conversion of oxygen in the tumor exterior induced ROS and the continuous consumption of oxygen amplified the hypoxia conditions in the tumor, which enhanced the surface-to-core penetration of nanoparticles into the hypoxia central tissue.
November 20, 2018: Chemical Communications: Chem Comm
Dongdong Wang, Ruohong Shi, Jiajia Zhou, Sixiang Shi, Huihui Wu, Pengping Xu, Hui Wang, Guoliang Xia, Todd E Barnhart, Weibo Cai, Zhen Guo, Qianwang Chen
Therapeutic effects of photodynamic therapy (PDT) remain largely limited because of tumor hypoxia. Herein, we report safe and versatile nanocatalysts (NCs) for endogenous oxygen generation and imaging-guided enhanced PDT. The NCs (named as PSP) are prepared by coating Prussian blue (PB) with mesoporous silica to load photosensitizer (zinc phthalocyanine, ZnPc), followed by the modification of polyethylene glycol chains. The inner PB not only acts like a catalase for hydrogen peroxide decomposition but also serves as a photothermal agent to increase the local temperature and then speed up the oxygen supply under near-infrared irradiation...
October 12, 2018: iScience
Mingle Li, Jing Xia, Ruisong Tian, Jingyun Wang, Jiangli Fan, Jianjun Du, Saran Long, Xiangzhi Song, James W Foley, Xiaojun Peng
Hypoxia, a quite universal feature in most solid tumors, has been considered as the "Achilles' heel" of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O2 -• ) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O2 -• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation...
October 26, 2018: Journal of the American Chemical Society
Ying Yang, Xue Yang, Huipeng Li, Chenzi Li, Huaqian Ding, Mengting Zhang, Yuxin Guo, Minjie Sun
Photodynamic therapy (PDT) as a promising noninvasive and effective treatment modality has been clinically approved for cancer therapy. However, the poor selectivity of tumor and hypoxia-induced resistance constrain PDT efficacy immensely. To further enhance PDT's potency, we developed a drug delivery system based on liposome combining PDT and chemotherapeutics. The lipophilic IR780 was loaded into the lipid bilayer while hydrophilic chemotherapeutic agent tirapazamine (TPZ) was encapsulated in the hydrophilic core...
October 12, 2018: Colloids and Surfaces. B, Biointerfaces
Pingping Liang, Xiaoyu Huang, Ya Wang, Dapeng Chen, Changjin Ou, Qi Zhang, Jinjun Shao, Wei Huang, Xiaochen Dong
Insufficient oxygen supply (hypoxia), short half-life (<40 ns) of singlet oxygen, and up-regulation of the heat shock protein expression in solid tumors impede the photodynamic and photothermal therapeutic efficacy. Herein, a near-infrared carrier-free nanoconjugate direct-acting antiviral (DAA) with synergistic antivascular activity and pH-responsive photodynamic/photothermal behavior was designed and synthesized to improve cancer treatment efficacy. Obtained by the self-assembly approach, the biocompatible DAA nanoparticles (NPs) displayed amplifying pH-responsive photodynamic/photothermal performance in an acidic tumor microenvironment due to the protonation of diethylaminophenyl units...
November 27, 2018: ACS Nano
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 24, 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...
November 14, 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 31, 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...
December 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 23, 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
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