title: Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release.
abstract: Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multi-drug delivery and release, as well as cellular responses to drug treatment.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China. zzshao@fudan.edu.cn.
authors.forename: Han
authors.initials: H
authors.lastname: Cao
authors.affiliation: Research Center for Analysis and Measurement, Fudan University, Shanghai, 200433, P. R. China. yuhongyang@fudan.edu.cn.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China. zzshao@fudan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, P. R. China. zzshao@fudan.edu.cn.
authors.forename: Zhengzhong
authors.initials: Z
authors.lastname: Shao
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D031541:Fluorescence Resonance Energy Transfer; D005978:Glutathione / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015122:Mercaptopurine / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism; D012542:Scattering, Radiation; D013059:Spectrum Analysis, Raman; D014468:Umbelliferones / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D006835:Hydrazones; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D006046:Gold; D004317:Doxorubicin; D015122:Mercaptopurine; D005978:Glutathione