Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

被引:1
作者
Mai, Zhijian [1 ,2 ]
Cao, Nengjie [1 ,2 ]
Cheng, Erzhuo [3 ,4 ]
Zeng, Zhiwen [1 ,2 ]
Feng, Yancong [1 ,2 ]
Wang, Yao [1 ,2 ]
French, Paddy J. [5 ]
Lee, Yi-Kuen [6 ,7 ]
Yang, Haihong [8 ]
Yang, Bin [3 ,4 ]
Li, Hao [1 ,2 ]
Zhou, Guofu [1 ,2 ]
机构
[1] South China Normal Univ, Inst Elect Paper Displays, South China Acad Adv Optoelect, Guangdong Prov Key Lab Opt Informat Mat & Technol, R China, Guangzhou 510006, Peoples R China
[2] South China Normal Univ, Natl Ctr Int Res Green Optoelect, Guangzhou 510006, Peoples R China
[3] Guangzhou Med Univ, Affiliated Hosp 6, Qingyuan Peoples Hosp, Guangzhou 511436, Peoples R China
[4] Guangzhou Med Univ, Sch Biomed Engn, Guangzhou 511436, Peoples R China
[5] Delft Univ Technol, BE Lab, EWI, NL-2628 CD Delft, Netherlands
[6] Hong Kong Univ Sci & Technol, Dept Mech & Aerosp Engn, Kowloon, Hong Kong 999077, Peoples R China
[7] Hong Kong Univ Sci & Technol, Dept Elect & Comp Engn, Kowloon, Hong Kong 999077, Peoples R China
[8] Guangzhou Med Univ, Affiliated Hosp 1, Dept Thorac Oncol, State Key Lab Resp Dis, Guangzhou 510006, Peoples R China
基金
中国国家自然科学基金;
关键词
small-molecule prodrug; Schiff base linkage; aggregation-induced emission; self-assembly; tumor-targeteddiagnosis and therapy; SMALL-MOLECULE PRODRUG; FLUORESCENCE; STRATEGIES; MECHANISM; DESIGN;
D O I
10.1021/acsanm.3c03611
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
To develop multifunctional small-molecule prodrugs is highly desirable for cancer treatment but remains challenging in intrinsic traceability. As an acid-cleavable linkage, a Schiff bases benefiting from its distinctive fluorescence quenching ability was selected to prepare a small-molecule prodrug with cancer-targeted and self-indicating. In this study, we designed and developed a multifunctional self-assembled nanobomb of amphiphilic TPE-Lenalidomide prodrug, which comprises a hydrophobic aggregation-induced emission (AIE) probe 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO) and a hydrophilic anticancer drug Lenalidomide via a Schiff base linkage. We investigated the synergistic effect of d-PET and C=N isomerization which would keep the fluorescence of TPE-Lenalidomide in the "always off" state by density functional theory (DFT) calculation. Once reaching the pathological site, such a vesicular nanobomb of TPE-Lenalidomide will be acidolyzed to release the AIE probe and Lenalidomide molecules simultaneously, consequently realizing high-efficiency effects of tumor imaging and cancer therapy (cell viability: normal cell L929, similar to 79.49%; cancer cell 4T1, similar to 27.08%; p = 0.000118). This work may pave an avenue to prepare small-molecule prodrugs for tumor-targeted diagnosis and cancer therapy.
引用
收藏
页码:19807 / 19817
页数:11
相关论文
共 55 条
[41]   Aggregation-Induced Emission Materials that Aid in Pharmaceutical Research [J].
Wang, Bingnan ;
Liu, Shanshan ;
Liu, Xiaolin ;
Hu, Rong ;
Qin, Anjun ;
Tang, Ben Zhong .
ADVANCED HEALTHCARE MATERIALS, 2021, 10 (24)
[42]   Small-Molecule Modulators Targeting Toll-like Receptors for Potential Anticancer Therapeutics [J].
Wang, Jiayu ;
Zhang, Jifa ;
Wang, Jiaxing ;
Hu, Xinyue ;
Ouyang, Liang ;
Wang, Yuxi .
JOURNAL OF MEDICINAL CHEMISTRY, 2023, 66 (10) :6437-6462
[43]   Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy [J].
Weigend, F ;
Ahlrichs, R .
PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2005, 7 (18) :3297-3305
[44]   Fluorescence turn on of coumarin derivatives by metal cations: A new signaling mechanism based on C=N isomerization [J].
Wu, Jia-Sheng ;
Liu, Wei-Min ;
Zhuang, Xiao-Qing ;
Wang, Fang ;
Wang, Peng-Fei ;
Tao, Si-Lu ;
Zhang, Xiao-Hong ;
Wu, Shi-Kang ;
Lee, Shuit-Tong .
ORGANIC LETTERS, 2007, 9 (01) :33-36
[45]   New sensing mechanisms for design of fluorescent chemosensors emerging in recent years [J].
Wu, Jiasheng ;
Liu, Weimin ;
Ge, Jiechao ;
Zhang, Hongyan ;
Wang, Pengfei .
CHEMICAL SOCIETY REVIEWS, 2011, 40 (07) :3483-3495
[46]   Bioinspired Coordination Micelles Integrating High Stability, Triggered Cargo Release, and Magnetic Resonance Imaging [J].
Xin, Keting ;
Li, Man ;
Lu, Di ;
Meng, Xuan ;
Deng, Jun ;
Kong, Deling ;
Ding, Dan ;
Wang, Zheng ;
Zhao, Yanjun .
ACS APPLIED MATERIALS & INTERFACES, 2017, 9 (01) :80-91
[47]   "One Stone, Four Birds" Ion Engineering to Fabricate Versatile Core-Shell Organosilica Nanoparticles for Intelligent Nanotheranostics [J].
Yan, Saisai ;
Sun, Panpan ;
Niu, Niu ;
Zhang, Zhijun ;
Xu, Weilin ;
Zhao, Siyi ;
Wang, Lei ;
Wang, Dong ;
Tang, Ben Zhong .
ACS NANO, 2022, 16 (06) :9785-9798
[48]   Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity [J].
Yao, Lu ;
Zhao, Mei-Mei ;
Luo, Qian-Wei ;
Zhang, Yi-Chi ;
Liu, Ting-Ting ;
Yang, Zhuo ;
Liao, Min ;
Tu, Pengfei ;
Zeng, Ke-Wu .
ACS NANO, 2022, 16 (06) :9228-9239
[49]   Therapeutic strategies of dual-target small molecules to overcome drug resistance in cancer therapy [J].
Ye, Jing ;
Wu, Junhao ;
Liu, Bo .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2023, 1878 (03)
[50]   Visualization of drug delivery processes using AIEgens [J].
Yuan, Youyong ;
Liu, Bin .
CHEMICAL SCIENCE, 2017, 8 (04) :2537-2546