化学学报 ›› 2020, Vol. 78 ›› Issue (7): 657-669.DOI: 10.6023/A20040132 上一篇    下一篇

所属专题: 分子探针、纳米生物学与生命分析化学

综述

肿瘤微环境刺激响应型上转换光动力诊疗体系的构建和发展

闫涛a, 刘振华b, 宋昕玥a, 张书圣a   

  1. a 临沂大学 化学化工学院 山东省肿瘤标志物检测技术重点实验室 临沂 276005;
    b 山东师范大学 化学化工与材料科学学院 济南 250014
  • 投稿日期:2020-04-29 发布日期:2020-08-06
  • 通讯作者: 宋昕玥, 张书圣 E-mail:songxinyue428@163.com;shushzhang@126.com
  • 作者简介:闫涛,自2019年起在临沂大学化学化工学院攻读硕士研究生学位.她的研究方向涉及上转换功能化纳米探针用于肿瘤标志物的检测、成像和诊疗一体化.
    刘振华,2015年在东北师范大学获得博士学位,同年8月加入山东师范大学化学化工与材料科学学院,现任副教授,硕士生导师,曾获吉林省百篇优秀博士论文(2016).目前其主要研究方向为有机分子合成方法学及其生物标记应用研究,近年来在Nat.Commun.,Angew.Chem.Int.Ed.,Org.Lett.,Anal.Chem.,Org.Chem.Front.,Sci.China Chem.等SCI期刊发表SCI论文20余篇.承担国家自然科学基金青年项目1项,山东省自然科学基金1项.
    宋昕玥,2016年1月在中国科学院兰州化学物理研究所获得博士学位,同年加入临沂大学生化分析研究所,现任副教授,硕士生导师.目前其主要研究方向为构建上转换功能化探针用于肿瘤标志物的检测、多模式成像和诊疗一体化的研究.近年来在Anal.Chem.,Trac-Trend.Anal.Chem.,Nanoscale,Chem.Commun.等期刊上发表SCI论文20余篇,承担国家自然科学基金青年项目1项,山东省重点研发计划1项,临沂市重点研发计划1项.
    张书圣,临沂大学教授、博士生导师,教育部生化分析创新团队负责人,国家杰出青年基金获得者、国家百千万人才工程入选者、国家有突出贡献的中青年专家、泰山学者攀登计划特聘教授、全国优秀教师、享受国务院政府特殊津贴.长期从事单分子检测、细胞成像与肿瘤精准诊疗、新仪器研制等研究.相关研究成果发表在Nat.Protoc.,Chem.Soc.Rev.,Adv.Funct.Mater.,J.Am.Chem.Soc.,Angew.Chem.,Chem.Sci.,Anal.Chem.,中国科学等SCI期刊上,发表论文共计178篇,总引用7500次,他引6798次,授权国家发明专利25项.2019年受邀在Springer Nature出版专著《核酸放大策略在生物传感、生物成像和生物医药方面的应用》(ISBN 978-981-13-7044-1).主持国家自然科学重点项目1项、杰出青年项目1项、重大仪器专项2项、其他国家级课题6项,获得省部级奖励6项.现任《Frontiers in Chemistry》副主编;《分析化学》、《应用化学》等杂志编委;中国有机电化学与工业联合会常务理事;山东省环境学会副理事长;中国化工学会、山东省腐蚀与防护学会理事.
  • 基金资助:
    项目受国家自然科学基金(No.21775063)、山东省自然科学基金(No.ZR2018ZC0231)和山东省重点研发计划(No.2017GGX40110)资助.

Construction and Development of Tumor Microenvironment Stimulus-Responsive Upconversion Photodynamic Diagnosis and Treatment System

Yan Taoa, Liu Zhenhuab, Song Xinyuea, Zhang Shushenga   

  1. a Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, China;
    b College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014
  • Received:2020-04-29 Published:2020-08-06
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 21775063), the Nature Science Foundation of Shandong Province (No. ZR2018ZC0231) and the Key Research Plan of Shandong Province (No. 2017GGX40110).

光动力治疗是一种新型的非侵入式肿瘤治疗方法,具有创伤性和毒性小、选择性好、无耐药性、可重复治疗等突出优点,在癌症的治疗上取得了显著的成效.为了增加光动力治疗的组织穿透深度,研究者提出构建基于上转换纳米颗粒(upconversion nanoparticles,UCNPs)的光动力诊疗探针(简称上转换光动力诊疗探针).基于发光共振能量转移过程,上转换光动力诊疗探针利用UCNPs在近红外光激发下发射的荧光激活负载的光敏剂发挥光动力疗效,有助于实现深层肿瘤的治疗.新型的上转换光动力诊疗探针通过多功能一体化的结构组合设计可以实现靶向运输、成像诊断以及刺激响应的按需治疗,是未来纳米医药发展的必然趋势.目前,研究者越来越关注构建基于肿瘤微环境刺激响应型上转换光动力诊疗体系,以提高治疗体系的靶向性,改善光动力治疗效果,并减小对周围正常组织的毒性.本工作主要讨论了基于pH、酶及过氧化氢刺激响应型上转换光动力诊疗体系的构建和发展,并对其发展前景进行了展望.

关键词: 光动力治疗, 上转换纳米颗粒, 肿瘤微环境, 刺激响应, 诊疗一体化

Photodynamic therapy (PDT) is a new type of non-invasive tumor therapy, which has the advantages of less trauma and toxicity, good selectivity, no drug resistance and repeatable treatment. Thus, PDT has achieved remarkable results in the treatment of cancer. In order to increase its depth of tissue penetration, researchers proposed to build novel PDT nano-theranostic systems based on upconversion nanoparticles (referred as upconversion photodynamic nanotheranostic system). Based on the luminescence resonance energy transfer process, upconversion photodynamic nanotheranostic systems use the emitted fluorescence of upconversion nanoparticles which is excited by the near-infrared laser to further excite the loaded photosensitizer, thus it is advantageous to the treatment of deep tumors. Via the multi-functional structure design, the newly developed upconversion photodynamic nanotheranostic agent could achieve the targeted transportation, imaging diagnosis and stimulation response for the achievement of on-demand treatment, which is the trend for the development of nanomedicine in the future. At present, researchers pay more and more attention to the construction of tumor microenvironment responsive nanotheranostic system, in order to improve the targeting to the tumor section, improve the PDT efficacy, and reduce the toxicity to the surrounding normal tissues. This work mainly discusses the construction and development of upconversion nanotheranostic systems based on the stimulation of pH, enzyme and hydrogen peroxide. In addition, we prospect its development in the future.

Key words: photodynamic therapy, upconversion nanoparticles, tumor microenvironment, stimulation response, theranostic