Enzyme-Driven Switchable Fluorescence-SERS Diagnostic Nanococktail for the Multiplex Detection of Lung Cancer Biomarkers

Comprehensive profiling of multiple protein targets plays a critical role in deeper understanding of specific disease conditions associated with high heterogeneity and complexity. Herein, we present the design and fabrication of smart programmable nanoarchitectures, which could integrate clinically...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2018-11, Vol.10 (45), p.38807-38818
Main Authors: Saranya, Giridharan, Joseph, Manu M, Karunakaran, Varsha, Nair, Jyothi B, Saritha, Valliamma N, Veena, Vamadevan S, Sujathan, Kunjuraman, Ajayaghosh, Ayyappanpillai, Maiti, Kaustabh K
Format: Article
Language:English
Subjects:
A549 Cells
Adenocarcinoma of Lung - chemistry
Adenocarcinoma of Lung - diagnosis
Biomarkers, Tumor - analysis
Cathepsin B - chemistry
Cell Line, Tumor
Fluorescent Dyes - chemistry
Gold - chemistry
Humans
Metal Nanoparticles - chemistry
Oligopeptides - chemistry
Optical Imaging - instrumentation
Optical Imaging - methods
Point-of-Care Systems
Spectrum Analysis, Raman - instrumentation
Spectrum Analysis, Raman - methods
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Summary:Comprehensive profiling of multiple protein targets plays a critical role in deeper understanding of specific disease conditions associated with high heterogeneity and complexity. Herein, we present the design and fabrication of smart programmable nanoarchitectures, which could integrate clinically relevant diagnostic modalities for the multiplexed detection of most prevalent panel of disease biomarkers present in lung cancer. The multiplex nanoprobes were prepared by attaching dual-functional Raman-active fluorogens onto spherical gold nanoparticles through a peptide linker, Phe-Lys-Cys (FKC), which is engineered with a cathepsin B (cathB) enzyme cleavage site. The presence of cathB induces the scission of FKC upon homing into the cancer cells, resulting in the release of the initially latent fluorophores with a concomitant quenching of the surface-enhanced Raman signal intensity, thereby realizing an on–off switching between the fluorescence and Raman modalities. The enzyme-triggered switchable nanoprobes were utilized for the simultaneous detection of pathologically relevant lung cancer targets by tethering with specific antibody units. The multiplex-targeted multicolor coded detection capability of the antitags was successfully developed as a valid protein screening methodology, which can address the unmet challenges in the conventional clinical scenario for the precise and early diagnosis of lung cancer.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b15583