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Qian Li, Lihong Sun, Mengmeng Hou, Qiubing Chen, Ruihao Yang, Lei Zhang, Zhigang Xu, Yuejun Kang, Peng Xue
Environmental stimuli, including pH, light and temperature, have been utilized for activating controlled drug delivery to achieve efficient antitumor therapeutics while minimizing undesirable side effects. In this study, a multifunctional nanoplatform based on hollow mesoporous copper sulfide nanoparticles (H-CuS NPs) was developed by loading the interior cavity of the NPs with a drug-loaded phase change material (PCM, 1-tetradecanol). Doxorubicin (DOX) and chlorin e6 (Ce6) were selected as the model chemotherapeutic drug and photosensitizer, respectively, which were encapsulated in H-CuS NPs via the PCM to form H-CuS@PCM/DOX/Ce6 (HPDC) NPs...
December 12, 2018: ACS Applied Materials & Interfaces
Zhenlu Yang, Jun Wen, Qing Wang, Yanjiao Li, Ying Zhao, Ying Tian, Xiaofen Wang, Xiongfeng Cao, Yunlei Zhang, Guangming Lu, Zhaogang Teng, Longjiang Zhang
Real-time monitoring of oxygen consumption is beneficial to predict treatment response and optimize therapeutic protocols for photodynamic therapy (PDT). In this work, we first demonstrate that deformable hollow mesoporous organosilica nanoparticles (HMONs) can be used to load [(Ru(dpp)3)]Cl2 for detecting oxygen (denoted as HMON-[(Ru(dpp)3)]Cl2). This nanoprobe shows significantly improved biocompatibility and high cellular uptake. In-vitro eperiments demonstrate that the HMON-[(Ru(dpp)3)]Cl2 can sensitively detect oxygen changes between 1 %-20 %...
December 10, 2018: ACS Applied Materials & Interfaces
Xiaoling Wang, Xumei Ouyang, Jinliang Chen, Ying Hu, Xiaoyi Sun, Zhenwei Yu
AIM: A photomedicine consisting of a core for photothermal therapy, a photosensitizer for photodynamic therapy, and a cancer-targeting moiety was fabricated to improve photosensitizer selectivity and antitumor efficiency. MATERIALS & METHODS: Hyaluronic acid-decorated polydopamine nanoparticles with conjugated chlorin e6 (HA-PDA-Ce6) were synthesized and characterized. Cell uptake, phototoxicity, penetration, distribution and therapeutic effects were evaluated...
December 4, 2018: Nanomedicine
Yifan Gao, Jing Wang, Dengfeng Hu, Yongyan Deng, Tingting Chen, Qiao Jin, Jian Ji
Photodynamic therapy (PDT) is believed to be a potent method for biofilm treatments. However, undesired damage to normal cells may be caused due to the nonselective nature of PDT. Therefore, targeted PDT is preferred on one hand to enhance antimicrobial effects and on the other hand to reduce cytotoxicity to normal cells. For this purpose, novel bacteria-targeted photosensitizer delivery micelles are fabricated, taking advantage of α-cyclodextrin (α-CD)/polyethylene glycol (PEG) supramolecular assembly. Hydrophilic antimicrobial peptide (AMP) Magainin I is covalently bound with PEG, working as a bacterial targeting group as well as the stabilizing shell of the supramolecular micelles...
November 30, 2018: Macromolecular Rapid Communications
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
Xu Hu, Hailong Tian, Wei Jiang, Aixin Song, Zhonghao Li, Yuxia Luan
Phototherapy as a promising cancer diagnostic and therapeutic strategy has aroused extensive attention. However, single-wavelength near-infrared (NIR) light-triggered combinational treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) is still a great challenge. Herein, a multifunctional micelle activated by a single-wavelength laser for simultaneous PTT and PDT as well as fluorescence imaging is developed. Briefly, new indocyanine green (IR820) is conjugated to d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via the linker 6-aminocaproic acid, and then, chlorin e6 (Ce6) is encapsulated into the micelles formed by TPGS-IR820 conjugates to fabricate TPGS-IR820/Ce6 micelles...
November 26, 2018: Small
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
Elisa Martella, Claudia Ferroni, Andrea Guerrini, Marco Ballestri, Marta Columbaro, Spartaco Santi, Giovanna Sotgiu, Massimo Serra, Davide Maria Donati, Enrico Lucarelli, Greta Varchi, Serena Duchi
Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX)...
November 20, 2018: International Journal of Molecular Sciences
Vladimír Puchart, Kristian B R Mørkeberg Krogh, Peter Biely
Glucuronoxylan selectively 3-O-acetylated on uronic acid-substituted xylopyranosyl residues was prepared by deacetylation of steam explosion-extracted aspenwood acetylglucuronoxylan by the CE6 acetylxylan esterase from Orpinomyces sp. The 3-O-acetylation of MeGlcA-substituted xylopyranosyl residues did not influence the mode of action of GH10, 11 and 30 xylanases, resulting in similar aldouronic acids as are found in alkali-extracted glucuronoxylan hydrolysates. In all three hydrolysates of the selectively acetylated glucuronoxylan, however, 3-O-acetylated aldouronic acids predominated over non-acetylated ones, suggesting that in native aspenwood xylan almost all MeGlcA-substituted Xylp residues are 3-O-acetylated...
February 1, 2019: Carbohydrate Polymers
Huan Liang, Zhanwei Zhou, Renjie Luo, Mangmang Sang, Bowen Liu, Minjie Sun, Wei Qu, Feng Feng, Wenyuan Liu
Photodynamic therapy relies on photosensitizers to generate cytotoxic reactive oxygen species (ROS) resulting in the apoptois of tumor cells. However, there is an antioxidant system that impedes the elevation of oxidation levels in tumor cells. Thus, photodynamic therapy may exhibit insufficient curative effects due to ungenerous reactive oxygen species levels. Herein, we describe tumor-specific activated photodynamic therapy using an oxidation-regulating strategy. Methods: We first synthesised a reactive oxygen species-sensitive amphipathic prodrug of gambogic acid-grafted hyaluronic acid (HA-GA)...
2018: Theranostics
Yang Kaizhen, Niu Ting, Luo Mengyu, Tang Lihua, Kang Ling
Photodynamic therapy (PDT) is a novel and non-invasive treatment that induces apoptosis and autophagy. Autophagy could play a pro-survival role, thus inhibiting autophagic activity might be a promising method to enhance the effectiveness of PDT for tumors. In the present study, photosensitizer Chlorin e6 (Ce6) was found to mainly locate in endoplasmic reticulum, and a few in mitochondria and lysosome. Chlorin e6 photodynamic therapy (Ce6-PDT) could kill human colon cancer SW620 cells by inducing apoptotic cell death, and autophagy also induced by Ce6-PDT in colon cancer cells...
October 21, 2018: Photodiagnosis and Photodynamic Therapy
O Benedicenti, C J Secombes, C Collins
Population growth, in vitro, of three Paramoeba perurans cultures, one polyclonal (G) and two clonal (B8, CE6, derived from G), previously shown to differ in virulence (B8 > G > CE6), was compared at 10 and 15 °C. B8 showed a significantly higher increase in attached and in suspended amoebae over time at 15 and 10 °C, respectively. CE6 and G also had significantly higher numbers of suspended amoebae at 10 °C compared with 15 °C at experiment termination. However, in contrast to B8, numbers of attached amoebae were significantly higher at 10 °C in CE6 but showed a similar trend in G at the end of the experiment...
October 25, 2018: Parasitology
Pei Pei, Chunyang Sun, Wei Tao, Jie Li, Xianzhu Yang, Jun Wang
Minimizing drug leakage at off-target sites and triggering sufficient drug release in tumor tissue are major objectives for effective nanoparticle (NP)-based cancer therapy. The current covalent and cleavable drug-NP conjugation strategy is promising but lacks high controllability to realize tumor-specific release. As a proof-of-concept, the reactive oxygen species (ROS)-activatable thioketal (TK) bond was explored as the linkage between doxorubicin (DOX) and polyphosphoester (PPE-TK-DOX). The Ce6@PPE-TK-DOX NPs constructed by co-self-coassembly of PPE-TK-DOX and the photosensitizer Ce6 efficiently prevented premature drug leakage in the off-target tissue and cells because of the high stability of the TK bond under physiological conditions...
October 11, 2018: Biomaterials
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
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
Yanlei Liu, Xiao Zhi, Wenxiu Hou, Fangfang Xia, Jingpu Zhang, Lexiang Li, Yuping Hong, Hao Yan, Chen Peng, Jesus Martinez de la Fuentea, Jie Song, Daxiang Cui
The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy...
October 18, 2018: Nanoscale
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