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Chemical Science
Volume 7 Number 1 January 2016 Pages 1–812
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EDGE ARTICLE Francesco Ricci et al. Electronic control of DNA-based nanoswitches and nanodevices
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DOI: 10.1039/C8SC03386B
Chemical Science Light-Induced Nitric Oxide Controllable Release Nano-platform
Photodynamic/Photothermal Synergistic Cancer Therapy
DOI: 10.1039/x0xx00000x www.rsc.org/
Ya Wang,a Xiaoyu Huang,a Yunyun Tang,a Jianhua Zou,a Peng Wang,a Yewei Zhang,c* Weili Si,a* Wei Huang,b Xiaochen Donga* The 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 microenvironment 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 diketopyrrolopyrrole core (denoted as DPP-NF). The DPP-NF nanoparticles (NPs) can be activated under weakly acidic condition of lysosome (pH 4.5-5.0) to generate reactive oxygen species (ROS) and enhance photothermal efficiency. The fluorescence detection demonstrated that NO controllable release can be realized by "on-off" of NF unit under NIR light irradiation or dark. The controllable NO release of DPP-NF NPs not only can trigger tumor cells death by DNA damage, but also overcome the PDT inefficiencies caused by hypoxia in tumor. Additionally, DPP-NF NPs displayed 45.6% photothermal conversion efficiency, which is superior to other reported DPP derivatives. In vitro studies showed that DPP-NF NPs possessed low dark toxicity and high phototoxicity with half-maximal inhibitory concentration about 38 µg/mL. In vivo phototherapy indicated that DPP-NF NPs exhibited excellent tumor phototherapeutic efficacy with passive targeting to tumor site via the enhanced permeability and retention (EPR) effect. These results highlight that the nano-platform has a promising potential in NO-mediated multimodal synergistic phototherapy in clinical.
Introduction Despite rapid development of diagnosis and treatment, cancer remains the biggest threat to human life and health in the world today. Traditional cancer treatments, such as chemotherapy,1-3 radiotherapy,4 and surgery, have some inevitable disadvantages. The drug resistance,
a
Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM),
Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211800, China. E-mail:
[email protected];
[email protected] b
Shaanxi Institute of Flexible Electronics (SIFE), Northwestern Polytechnical University (NPU),
127 West Youyi Road, Xi'an 710072, China. c
Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital, Medical School,
Southeast University, Nanjing 210009, China. E-mail:
[email protected]
large side effects, no targeting, and normal cells damage further reduce the survival rate of patients. Photodynamic therapy (PDT) and photothermal therapy (PTT) have now been considered as novel alternatives to traditional oncology treatments with high selectivity, low toxicity, no drug resistance and lower non-invasive. 5-13 PDT and PTT depend on photon energy absorbed by photosensitizers to generate reactive oxygen species (ROS) or heat, causing damage or death of blood vessels and tumor cells.14-18 Owing to the difference of pH value between tumor microenvironment (pH 4.5-5.0) and normal tissues (pH 7.4),19-22 smart pH-activated photosensitizers are extremely desirable. The lysosomes with weak acidity in tumour cells can act as a pH-activated reactor,23-25 which provides the most effective approach for imaging and therapy in vitro and in vivo.
†Electronic Supplementary Informa@on (ESI) available: [details of any supplementary information available should be included here]. See DOI: 10.1039/x0xx00000x
Chem Sci., 2013, 00, 1-3 | 1
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Chemical Science Accepted Manuscript
Open Access Article. Published on 29 August 2018. Downloaded on 8/30/2018 1:49:01 AM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Based on Diketopyrrolopyrrole Derivatives for pH-Responsive Received 00th January 2018, Accepted 00th January 2018
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DOI: 10.1039/C8SC03386B
Chemical Science
As a star molecule, NO is ubiquitous in organisms and is involved in the regulation of blood multicellular activities, including vascular growth, smooth muscle relaxation, immune response, apoptosis, and synaptic transmission. In addition to its role in normal physiological activities, a large number of studies have confirmed that it is closely related to the occurrence and development of many diseases, especially tumours.26-29 The biological effect of NO is a double-edged sword with the concentration dependence. Generally, continuous low concentrations (pM-nM) of NO have a tumour promoting effect on the growth of tumour vascular.30-32 However, high concentration of NO (>mM) may cause NO poisoning in the blood. When NO maintains at certain concentrations (nM-mM), it could suppress tumour growth and display an anti-tumour effect. The main mechanisms of NO antitumour effect are: (1) Affecting the energy metabolism of cells and causing tumour cells deaths owing to energy metabolism disorders. (2) Binding with superoxide anions in cells and generating nitrogen/oxygen free radicals to damage DNA. (3) Mediating macrophage activation against tumour and inhibiting tumour metastasis by restraining platelet aggregation. (4) Inducing the apoptosis of tumour cells by activating of p53 expression. As a gaseous free radical species biosynthesized in living cells, NO is a short-lived (< 1 s) pleiotropic molecule with small diffusion radius (
