title: Compact, Programmable, and Stable Biofunctionalized Upconversion Nanoparticles Prepared through Peptide-Mediated Phase Transfer for High-Sensitive Protease Sensing and in Vivo Apoptosis Imaging.
abstract: Protease represents an important class of biomarkers for disease diagnostics and drug screening. Conventional fluorescence-based probes for in vivo protease imaging suffer from short excitation wavelengths and poor photostability. Upconversion nanoparticles (UCNPs) hold great promise for biosensing and bioimaging because of their deep-tissue excitability, robust photostability, and minimal imaging background. However, producing highly stable and compact biofunctionalized UCNP probes with optimal bioresponsivity for in vivo imaging of protease activities still remains challenging and has not been previously demonstrated. Herein, we report facile preparation of highly compact and stable biofunctionalized UCNPs through peptide-mediated phase transfer for high-sensitive detection of protease in vitro and in vivo. We demonstrate that the polyhistidine-containing chimeric peptides could displace oleic acid molecules capped on UCNPs synthesized in organic solvents and, thereby, directly transfer UCNPs from the chloroform phase to the water phase. The resulting UCNPs possess high stability, programmable surface properties, and a compact coating layer with minimized thickness for efficient luminescence resonance energy transfer (LRET). On the basis of this strategy, we prepared LRET-based UCNP probes with optimal bioresponsivity for in vitro high-sensitive detection of trypsin and in vivo imaging of apoptosis for chemotherapy efficacy evaluation. The reported strategy could be extended to construct a variety of peptide-functionalized UCNPs for various biomedical applications.
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: He
authors.affiliation: †Key Laboratory of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, and ‡Testing and Analysis Center, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use; D014357:Trypsin / Q000302:isolation & purification*
chemical_list: D010455:Peptides; D014357:Trypsin
keywords: biosensing; in vivo imaging; peptide; phase transfer; protease; upconversion nanoparticle