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Hypoxia photodynamic therapy

Guangxu Lan, Kaiyuan Ni, Samuel S Veroneau, Xuanyu Feng, Geoffrey T Nash, Taokun Luo, Ziwan Xu, Wenbin Lin
Nanoscale metal-organic frameworks (nMOFs) have shown great potential as nanophotosensitizers for photodynamic therapy (PDT) owing to their high photosensitizer loadings, facile diffusion of reactive oxygen species (ROSs) through their porous structures, and intrinsic biodegradability. The exploration of nMOFs in PDT, however, remains limited to an oxygen-dependent type II mechanism. Here we report the design of a new nMOF, Ti-TBP, composed of Ti-oxo chain second building units (SBUs) and photosensitizing 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) ligands, for hypoxia-tolerant type I PDT...
February 19, 2019: Journal of the American Chemical Society
Na Tian, Weize Sun, Xusheng Guo, Jian Lu, Chao Li, Yuanjun Hou, Xuesong Wang, Qianxiong Zhou
Three chloromethyl-modified Ru(ii) complexes were designed and synthesized as mitochondria targeting photosensitizers, which can generate carbon radicals in the presence of NADH under visible light irradiation, cause DNA cleavage and covalent binding in Ar-saturated solutions, and lead to apoptosis of human ovarian carcinoma SKOV-3 cells under hypoxic conditions (3% O2), demonstrating a new mode of type I mechanism to overcome the limitation of hypoxia in photodynamic therapy (PDT).
February 12, 2019: Chemical Communications: Chem Comm
Pei Liu, Jinghua Ren, Yuxuan Xiong, Zhe Yang, Wei Zhu, Qianyuan He, Zushun Xu, Wenshan He, Jing Wang
Mitochondria, which are a major source of adenosine triphosphate (ATP) and apoptosis regulators, are the key organelles that promote tumor cell proliferation, and their dysfunction affects tumor cell behavior. Additionally, mitochondria have been shown to play a central role in the biosynthesis of protoporphyrin IX (PpIX), which is a widely used photosensitizer that has been used for tumor detection, monitoring and photodynamic therapy. Nevertheless, photosensitizers administrated exogenously are often restricted by limited bioavailability...
February 2, 2019: Biomaterials
Wuyang Yu, Tao Liu, Mingkang Zhang, Zixu Wang, Jingjie Ye, Chu-Xin Li, Wenlong Liu, Runqing Li, Jun Feng, Xian-Zheng Zhang
Hypoxia, a ubiquitously aberrant phenomenon implicated in tumor growth, causes severe tumor resistance to therapeutic interventions. Instead of the currently prevalent solution through intratumoral oxygen supply, we put forward an "O2-economizer" concept by inhibiting O2 consumption of cell respiration to spare endogenous O2 to overcome the hypoxia barrier. A nitric oxide (NO) donor responsible for respiration inhibition and a photosensitizer for photodynamic therapy (PDT) are co-loaded into PLGA nanovesicles to provide a PDT-specific O2 economizer...
January 30, 2019: ACS Nano
Ruyuan Song, Sheng Peng, Qingguang Lin, Ma Luo, Ho Yin Chung, Yanling Zhang, Shuhuai Yao
Tumor hypoxia is a significant factor leading to the resistance of tumors to treatments, especially for photodynamic therapy and radiotherapy where oxygen is needed to kill cancer cells. Oxygen delivery agents such as oxygen-saturated perfluorocarbon nanoemulsions or lipid oxygen microbubbles have been employed to supply oxygen to the hypoxic tumors with the ultrasound activation. Such oxygen delivery systems are still associated with several drawbacks including premature oxygen release and the dependence of external stimuli...
January 30, 2019: Langmuir: the ACS Journal of Surfaces and Colloids
Shengnan Ma, Jie Zhou, Yuxin Zhang, Bo Yang, Yiyan He, Chen Tian, Xianghui Xu, Zhongwei Gu
The efficacy of photodynamic therapy (PDT) in the solid tumor is hampered by many challenges, including its oxygen self-consuming nature, insufficient oxygen levels within the hypoxic tumor microenvironment, and limited penetration of photosensitizers within tumors. Herein, we develop the IR780@O2-SFNs/iRGD as an oxygen self-sufficient and tumor-penetrating nanoplatform, which consists of IR780 loaded pH-sensitive fluorocarbon functionalized nanoparticles (SFNs) and iRGD as a tumor targeting peptide that can penetrate deeper within the tumor...
January 29, 2019: ACS Applied Materials & Interfaces
Rui Xia, Xiaohua Zheng, Xiuli Hu, Shi Liu, Zhigang Xie
The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. In order to address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature...
January 21, 2019: ACS Applied Materials & Interfaces
Shan Sun, Jingqin Chen, Kai Jiang, Zhongdi Tang, Yuhui Wang, Zhongjun Li, Chengbo Liu, Aiguo Wu, Hengwei Lin
Photo-mediated cancer therapy, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), have received tremendous attention in recently years thanks to their noninvasive and stimuli-responsive features. The single mode of PTT or PDT, however, shows obvious drawbacks, either requiring high power laser irradiation to generate enough heat or only providing limited efficacy due to the hypoxia nature inside tumors. In addition, the reported synergistic PTT/PDT usually utilized two excitation sources to separately activate PTT and PDT, and the problem of high power laser irradiation for PTT was still not well solved...
January 16, 2019: ACS Applied Materials & Interfaces
Run-Qing Li, Chi Zhang, Bo-Ru Xie, Wu-Yang Yu, Wen-Xiu Qiu, Han Cheng, Xian-Zheng Zhang
This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)3 2+ ) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C3 N4 ) for the first time. While exposured to two-photon laser, Ru(bpy)3 2+ was activated to generate singlet oxygen (1 O2 ) and Fe-C3 N4 was triggered to split water for oxygen supply in the mean time...
December 17, 2018: Biomaterials
Dandan Ma, Caixia Huang, Jing Zheng, Wenyu Zhou, Jianru Tang, Weiju Chen, Jishan Li, Ronghua Yang
Mitophagy, as a crucial metabolic process, plays an essential role in maintaining cellular and tissue homeostasis. Various stresses especially hypoxia could improve intracellular reactive oxygen species (ROS) level to induce mitophagy. However, high-specific fluorescence imaging of mitophagy in living cells under hypoxia is still a challenge. Based on this, we report an azoreductase-responsive nanoprobe (termed Micelle@Mito-rHP@TATp, MCM@TATp) by encapsulating cationic spiropyrane derivative (Mito-rHP) to realize specific imaging of mitophagy in living cells under hypoxia...
December 19, 2018: Analytical Chemistry
Zhimei He, Yunlu Dai, Xiangli Li, Dan Guo, Yijing Liu, Xiaolin Huang, Jingjing Jiang, Sheng Wang, Guizhi Zhu, Fuwu Zhang, Lisen Lin, Jun-Jie Zhu, Guocan Yu, Xiaoyuan Chen
During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2 -consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia-activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido-/photosensitizer-terminated UiO-66 nanoscale metal-organic frameworks (UiO-66-H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered...
December 19, 2018: Small
Sooseok Im, Junseok Lee, Dongsik Park, Areum Park, You-Me Kim, Won Jong Kim
A key factor for successful cancer immunotherapy (CIT) is the extent of antigen presentation by dendritic cells (DCs) that phagocytize tumor-associated antigens (TAA) in the tumor site and migrate to tumor draining lymph nodes (TDLN), for the activation of T cells. Although various types of adjuvant delivery have been studied to enhance the activity of the DCs, poor delivery efficiency and depleted population of tumor infiltrating DCs have limited the efficacy of CIT. Herein, we report a hypoxia-responsive mesoporous silica nanocarrier (denoted as CAGE) for an enhanced CIT assisted by photodynamic therapy (PDT)...
December 18, 2018: ACS Nano
Ya Wang, Xiaoyu Huang, Yunyun Tang, Jianhua Zou, Peng Wang, Yewei Zhang, Weili Si, Wei Huang, Xiaochen Dong
Emerging treatment approaches, such as gas therapy (GT), photodynamic therapy (PDT) and photothermal therapy (PTT), have received widespread attention. The development of an intelligent multifunctional nano-platform responding to tumor microenvironments for multimodal therapy is highly desirable. Herein, a near-infrared (NIR) light-responsive nitric oxide (NO) photodonor (4-nitro-3-trifluoromethylaniline, NF) and a pH-sensitive group (dimethylaminophenyl) have been introduced into a diketopyrrolopyrrole core (denoted as DPP-NF)...
November 14, 2018: Chemical Science
Xunzhou Yu, Danfeng He, Ximu Zhang, Hongmei Zhang, Jinlin Song, DeZhi Shi, Yahan Fan, Gaoxing Luo, Jun Deng
Since generating toxic reactive oxygen (ROS) is largely dependent on oxygen, bacteria infected wounds hypoxia significantly inhibits photodynamic therapy's (PDT) antibacterial efficiency. Therefore, a novel therapeutic method for eradicating multidrug-resistant bacteria is developed based on the light-activated alkyl free radical generation (that is oxygen-independent). According to the polydopamine coated carboxyl graphene (PDA@CG), an initiator-loaded and pH-sensitive heat-producible hybrid of bactericides was synthesized...
December 7, 2018: ACS Applied Materials & Interfaces
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
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