Lysosome-Targeted Gold Nanotheranostics for In Situ SERS Monitoring pH and Multimodal Imaging-Guided Phototherapy

Abstract

The integration of surface-enhanced Raman spectrum (SERS) and fluorescence-photoacoustic multimodal imaging in near-infrared photothermal therapy is highly desirable for cancer theranostic. However, typically, gold nanotheranostics usually require an additional modification of fluorophores and complex design refinements. In this work, by integrating surface-modified cysteine-hydroxyl merocyanine (CyHMC) molecules onto AuNRs, a novel lysosome-targeted gold-based nanotheranostics AuNRs-CyHMC that combines the specificity of Raman spectrum, the speed of fluorescence imaging, and deep penetration of photoacoustic imaging was successfully fabricated. Interestingly, fluorescence and Raman signals in this AuNRs-CyHMC system do not interfere, but it has pH-sensitive Raman signals and selffluorescence localization ability under different excitation wavelengths. Fluorescence co-localization experiments further confirmed the lysosome-targeting ability of AuNRs-CyHMC. Typically, the proposed nanotheranostics were capable of SERS monitoring pH changes in both phosphate-buffered saline and living cells. Meanwhile, in vitro and in vivo experiments revealed that AuNRs-CyHMC possessed excellent fluorescence-photoacoustic performance and could be used for multimodal imaging-guided photothermal therapy. Furthermore, our work implied that gold nanotheranostics can provide great potential for cancer diagnosis and treatment.

Charge Neutralization Strategy to Construct Salt-Tolerant and Cell-Permeable Nanoprobes: Application in Ratiometric Sensing and Imaging of Intracellular pH

“…As depicted in Figure S12, a stronger fluorescence intensity in the green channel was observed in HeLa cells incubated with HPTS-PAH-AuNCs, indicating enhanced cell permeability of HPTS by charge neutralization of PAH-AuNCs. Typically, passively targeted gold nanomaterials 45,46 and cationic polyamines 47,48 were usually endocytosed into cells and mainly located in lysosomes. For the proposed HPTS-PAH-AuNCs probe, the absence of other organelle-targeting modifications on its surface led to a low probability of altering the endocytic pathway into the cell.…”

Applications of Surface-Enhanced Raman Scattering in Biochemical and Medical Analysis

“…For example, gold nanorods labeled with a pH-sensitive dye (cysteine-hydroxyl merocyanine) were used to monitor pH in lysosomes. Their localization was confirmed by the fluorescence measured from the dye, and laser irradiation caused metal heating to 60 • C, resulting in a significant decrease in solid tumors in living mice, on which the sensor was ultimately tested (Wen et al, 2021). Li et al (2018) applied this procedure for human breast tumor specimens by staining 5-µm thin sections with a mixture of four antibody-labeled SERS probes, successfully targeting cerbB2, oestrogen, progesterone, and epidermal growth factor receptors expressed in the tissues.…”

“…The SERS spectroscopy has been widely used for analyzing various biosamples, including DNA (Pyrak et al, 2019;Zhang et al, 2019a), RNA (Lee et al, 2019;Han et al, 2021), cancer markers (Choi et al, 2020), bacteria (Andrei et al, 2021), viruses (Chen et al, 2020), genes (Vo-Dinh et al, 2002), drugs (Jaworska et al, 2016), pathological markers on cellular membranes and tissues (Wallace and Masson, 2020), other biomolecules, ion concentrations, and redox potential in cells (Jaworska et al, 2021), and even in vivo SERS measurements on mice (Wen et al, 2021). In many cases, the results obtained are at a level of detection not achievable by other analytical methods.…”

Surface‐Enhanced Raman Probes Based on Gold Nanomaterials for in vivo Diagnosis and Imaging

“…By functionalizing metal substrates and incorporating Raman signal molecules, targeted Raman imaging or pH, temperature and other characteristic Raman signals can be easily obtained. [35][36][37][38] More importantly, SERS nanoprobes show specific spectral "fingerprints" that allow multiple targets to be sensed at the same time. [39] Thus, it can be said that SERS nanoprobes have been evolved into important tools for the biomedicine diagnostics and imaging applications.…”

“…Most often, the SERS technique greatly enhances the intensity of the Raman signal, which may aid in improving the sensitivity of the Raman signal and allowing the Raman signal to be collected in a shorter time, and finally provides good technical support for Raman imaging. By functionalizing metal substrates and incorporating Raman signal molecules, targeted Raman imaging or pH, temperature and other characteristic Raman signals can be easily obtained [35–38] . More importantly, SERS nanoprobes show specific spectral “fingerprints” that allow multiple targets to be sensed at the same time [39] .…”