title: Ratiometric Monitoring of Intracellular Drug Release by an Upconversion Drug Delivery Nanosystem.
abstract: Nanoscale drug delivery systems have been widely investigated due to their well-recognized advantages including controlled delivery of chemotherapeutic agents, enhanced therapeutic effectiveness, and reduced adverse effects compared to conventional chemotherapy with small molecules. However, further progress in the use of nanoscale delivery systems in clinical applications has been hampered by pharmacokinetic studies in biological samples which were associated with significant experimental challenges. Here, we report a rational ratiometric approach to monitor drug release kinetics by quantitatively investigating luminescence resonance energy transfer (LRET) from upconversion nanoparticles to the antitumor drug doxorubicin (DOX). Specifically, DOX molecules within the shell of mesoporous silica-coated upconversion nanoparticles selectively quenched the green emission of upconversion nanoparticles, while the intensity of red emission was essentially unaltered. Consequently, when DOX was gradually released, a steady recovery of green emission was observed. The ability to monitor the intensity ratio of green-to-red luminescence enabled a rational design for real-time investigation of drug delivery release kinetics. Importantly, the internal standard effect of red emission made this ratiometric approach suitable for complex biological microenvironments.
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Chemistry and The Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Fuyou
authors.initials: F
authors.lastname: Li
mesh_terms: D004317:Doxorubicin / Q000737:chemistry* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D049449:Luminescence; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D016062:Porosity; D012822:Silicon Dioxide
chemical_list: D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: LRET; drug release; intracellular imaging; monitoring; nanocarriers; ratiometric; upconverting luminescence