pH-Driven Targeting Nanoprobe with Dual-Responsive Drug Release for Persistent Luminescence Imaging and Chemotherapy of Tumor

• Published in: Analytical chemistry (Washington) Vol. 92; no. 1; pp. 1179 - 1188
• Main Authors: Zhang, Hong-Jiao, Zhao, Xu, Chen, Li-Jian, Yang, Cheng-Xiong, Yan, Xiu-Ping
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.01.2020
• Subjects: A549 Cells; Analytical chemistry; Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Cathepsin B; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chemotherapy; Core-shell structure; Diagnosis; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug delivery; Drug delivery systems; Drug Liberation; Drug Screening Assays, Antitumor; Female; Glutathione; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Imaging; Liver Neoplasms, Experimental - diagnostic imaging; Luminescence; Medical diagnosis; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; Optical Imaging; Peptides; Peptides - chemistry; Peptides - pharmacology; pH effects; Silica; Silicon dioxide; Silicon Dioxide - chemistry; Silicon Dioxide - pharmacology; System effectiveness; Target recognition; Tumor cells; Tumor Microenvironment - drug effects; Tumors
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.9b04318

Multifunctional nanoprobes with both imaging and drug delivery capabilities represent an emerging approach to the diagnosis and treatment of tumor. However, poor accumulation in tumor cells and low drug availability are the main limitations for their further application. Here we show a pH-driven targeting nanoprobe with dual-responsive drug release for persistent luminescence imaging and chemotherapy of tumor. The nanoprobe is constructed by conjugating the pH-low-insertion-peptide (pHLIP) to the surface of the core–shell structure of mesoporous silica-coated persistent luminescence nanoparticles (MSPLNPs) with the peptide GFLG and disulfide bond as bridges. The pHLIP functionalized nanoprobe exhibits higher cellular uptake for A549 and HepG2 cells in an acidic extracellular microenvironment (pH < 6.5) than in normal physiological condition (pH 7.4). The nanoprobe possesses well-defined NIR persistent luminescence performance and can be effectively accumulated in the tumor site, leading to the visual HepG2 tumor target imaging without autofluorescence interference. Furthermore, the nanoprobe realizes the dual-responsive release of doxorubicin loaded in the mesoporous channels in systems containing cathepsin B and glutathione, and can effectively kill tumor cells and inhibit the growth of tumor. This integrated nanoprobe possesses great potential for the diagnosis and treatment of tumors with high specificity and efficiency.