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dual-stimuli responsive near-infrared emissive carbon dots/hollow mesoporous silica-based integrated theranostics platform for real-time visualized drug delivery

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Nano Research 2021年第11期14卷 4264-4273页

作者： Zhongyin Chen Tao Liao Lihui Wan Ying Kuang Chang Liu Junlin Duan Xiangyu Xu Ziqiang Xu Bingbing Jiang Cao Li Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and MinistryHubei Key Laboratory of Polymer MaterialsHubei UniversityWuhan430062China Glyn O.Philips Hydrocolloid Research Centre at HUT Hubei University of TechnologyWuhan430068China

Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerged as a promising strategy for cancer therapy. Herein, tumor microenvironment (TME) sensitive nanocarriers based on doxorubicin hydrochloride (DOX), NIR emitting carbon dots (C-dots), hollow mesoporous silica nanoparticles (HMSN) and anionic polymer citraconic anhydride-modified polylysine (PLL(cit)) are fabricated for imaging guided drug delivery. The NIR emitting C-dots were conjugated onto the surface of HMSN via disulfide bonds which can be reduced by intracellular glutathione (GSH) and result in the release of DOX into cells. And then the PLL(cit) was grafted on the surface of the nanocarriers to endow the nanocarriers with charge convertible property in mildly acidic TME (pH = 6.50) which results in prolonged blood circulation time and enhanced cellular internalization. The in vitro and in vivo experiments confirmed that the dual pH/GSH responsive features of nanocarriers can eliminate the tumor tissues effectively and elicit much slighter side effects. Moreover, since the fluorescence of C-dots can be recovered after the reduction of disulfide bonds and selectively accumulation of nanocarriers around tumor tissue, the DOX@HMSN-SS-C-dots-PLL(cit) can be served as a promising NIR fluorescence probe for targeted imaging of tumor tissue. As a kind of multifunctional nanocarrier with NIR fluorescent imaging and therapeutic functions, the theranostic nanocarriers hold great potential for tumor therapy and in vivo imaging of tumor tissue.

关键词： charge-reversal hollow mesoporous silica nanoparticles near-infrared emissive carbon dots dual-stimuli responsive

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Redox dual-stimuli responsive drug delivery systems for improving tumor-targeting ability and reducing adverse side effects

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Asian Journal of Pharmaceutical Sciences 2020年第3期15卷 311-325页

作者： Ruirui Li Feifei Peng Jia Cai Dandan Yang Peng Zhang School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Cancer is a big challenge that has plagued the human beings for ages and one of the most effective treatments is chemotherapy. However, the low tumor-targeting ability limits the wide clinical application of chemotherapy. The microenvironment plays a critical role in many aspects of tumor genesis. It generates the tumor vasculature and it is highly implicated in the progression to metastasis. To maintain a suitable environment for tumor progression, there are special microenvironment in tumor cell, such as low pH, high level of glutathione(GSH) and reactive oxygen species(ROS), and more special enzymes, which is different to normal cell. Microenvironment-targeted therapy strategy could create new opportunities for therapeutic targeting. Compared to other targeting strategies, microenvironment-targeted therapy strategy will control the drug release into tumor cells more accurately. Redox responsive drug delivery systems(DDSs) are developed based on the high level of GSH in tumor cells. However, there are also GSH in normal cell though its level is lower. In order to control the release of drugs more accurately and reduce side effects, other drug release stimuli have been introduced to redox responsive DDSs. Under the synergistic reaction of two stimuli, redox dual-stimuli responsive DDSs will control the release of drugs more accurately and quickly and even increase the accumulation. This review summarizes strategies of redox dual-stimuli responsive DDSs such as pH, light, enzyme, ROS, and magnetic guide to delivery chemotherapeutic agents more accurately, aiming at providing new ideas for further promoting the drug release,enhancing tumor-targeting and improving anticancer effects. To better illustrate the redox dual-stimuli responsive DDS, preparations of carriers are also briefly described in the review.

关键词： Chemotherapy Drug delivery system Redox responsive dual-stimuli responsive Tumor-targeting

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“dual-Lock-dual-Key”Controlled Second Near-Infrared Molecular Probe for Specific Discrimination of Orthotopic Colon Cancer and Imaging-Guided Tumor Excision

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CCS Chemistry 2022年第11期4卷 3609-3626页

作者： Kun Dou Chen Fan Wenqi Feng Yao Kong Yunhui Xiang Zijun Wang Zhihong Liu College of Chemistry and Molecular Sciences Wuhan UniversityWuhan 430072 Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules and College of Chemistry and Chemical Engineering Hubei UniversityWuhan 430062

Fluorescence imaging in the second infrared window(1000-1700 nm)has emerged as a promising approach to tumor ***,the currently available second near-infrared(NIR-II)imaging agents are based on the“always on”modality or single biomarker activation,which are subject to limited imaging contrast,nonspecific response,and even false-positive ***,we developed a H2S/H+dual-stimuli responsive NIR-II fluorescent probe,WH-N3,for precise tumor delimitation and intraoperative fluorescence-guided surgical ***-N3 itself is nonfluorescent,and it can only light up through synergistic activation by H2S and in the tumor acidic environment(TEM).Such a“duallock-dual-key”strategy-based activatable probe exhibited significantly higher tumor-to-normal tissue(T/N)ratios than the“always on”agent(ICG)and single parameter responsive counterpart probes in the imaging of colon tumors,which overexpresses ***-N3 was also able to visualize the tumor-derived endogenous H2S fluctuation and accurately differentiate tumor types based on H2S content *** excitingly,under the guidance of the probe’s highly specific NIR-II fluorescence,a tiny orthotopic colon tumor with diameter down to 0.8 mm was facilely *** expect our dual-stimuli responsive strategy will contribute more reliable tools for specific discrimination and imaging-guided excision of tumor.

关键词： NIR-II fluorescence dual-stimuli responsive activatable probe orthotopic colon cancer imaging-guided tumor resection

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