Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy

Xu Zhao,Xiu-Ping Yan,Cheng-Xiong Yang,Li-Gong Chen

doi:10.1038/ncomms14998

Abstract

The integrated functions of diagnostics and therapeutics make theranostics great potential for personalized medicine. Stimulus-responsive therapy allows spatial control of therapeutic effect only in the site of interest, and offers promising opportunities for imaging-guided precision therapy. However, the imaging strategies in previous stimulus-responsive therapies are ‘always on’ or irreversible ‘turn on’ modality, resulting in poor signal-to-noise ratios or even ‘false positive’ results. Here we show the design of dual-stimuli-responsive and reversibly activatable nanoprobe for precision tumour-targeting and fluorescence-guided photothermal therapy. We fabricate the nanoprobe from asymmetric cyanine and glycosyl-functionalized gold nanorods (AuNRs) with matrix metalloproteinases (MMPs)-specific peptide as a linker to achieve MMPs/pH synergistic and pH reversible activation. The unique activation and glycosyl targetibility makes the nanoprobe bright only in tumour sites with negligible background, while AuNRs and asymmetric cyanine give synergistic photothermal effect. This work paves the way to designing efficient nanoprobes for precision theranostics.

Highlights

The integrated functions of diagnostics and therapeutics make theranostics great potential for personalized medicine
The prepared peptide modified asymmetric cyanine (Pep-Acy) provided a terminal-SH group to further conjugate the AuNRs via the Au–S bond to obtain a matrix metalloproteinases (MMPs)/pH dual-stimuli responsive and pH reversibly activated multifunctional nanoprobe (Pep-Acy@AuNRs)
The intracellular Au content in the cells treated with PepAcy/Glu@AuNRs showed about 2.5-fold increase compared with the above controls (Supplementary Fig. 12). These results indicate that Pep-Acy/Glu@AuNRs were successfully internalized into the SCC-7 cells and the cell internalization was obviously enhanced by glycosyl due to the dual-targeting effects of both enhanced permeation and retention (EPR) effect and glucose transported protein (GLUT) receptor mediated active tumour-targeting effect

Summary

Introduction

The integrated functions of diagnostics and therapeutics make theranostics great potential for personalized medicine. We show the design of dual-stimuli-responsive and reversibly activatable nanoprobe for precision tumour-targeting and fluorescence-guided photothermal therapy. The unique activation and glycosyl targetibility makes the nanoprobe bright only in tumour sites with negligible background, while AuNRs and asymmetric cyanine give synergistic photothermal effect. We report a strategy to design and fabricate dualstimuli synergistically and reversibly activatable multifunctional nanoprobes for in vivo tumour-targeting and specific imagingguided precision photothermal therapy. Asymmetric cyanine serves as both the tumour-specific imaging probe and auxiliary photothermal agent due to its reversible pH-responsive near-infrared absorption and fluorescence[42]. A MMPs-specific peptide sequence (H2N– GPLGVRGC–SH) serves as the linker between the AuNRs and the asymmetric cyanine near-infrared probe to build MMPs/pH synergistically and reversibly activatable theranostic nanoprobe. The asprepared theranostic nanoprobe exhibits precision tumour-targeted imaging with ultra-high specificity and negligible background, and possesses ultra-strong photothermal effect without obvious side-effect, holding great promising for theranostic application

Methods

Results

Conclusion