Theranostic Gold Nanoantennas for Simultaneous Multiplexed Raman Imaging of Immunomarkers and Photothermal Therapy

Abstract

In this study, we demonstrate the theranostic capability of actively targeted, site-specific multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. By utilizing multiplexed surface-enhanced Raman scattering (SERS) imaging, enabled by the narrow peak widths of Raman signatures, we simultaneously targeted immune checkpoint receptor programmed death ligand 1 (PDL1) and the epidermal growth factor receptor (EGFR) overexpressed in TNBC cells. A 1:1 mixture of MGNs functionalized with anti-PDL1 antibodies and Raman tag 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and MGNs functionalized with anti-EGFR antibodies and Raman tag para-mercaptobenzoic acid (pMBA) were incubated with the cells. SERS imaging revealed a cellular traffic map of MGN localization by surface binding and receptor-mediated endocytosis, enabling targeted diagnosis of both biomarkers. Furthermore, cells incubated with anti-EGFR–pMBA–MGNs and illuminated with an 808 nm laser for 15 min at 4.7 W/cm2 exhibited photothermal cell death only within the laser spot (indicated by live/dead cell fluorescence assay). Therefore, this study not only provides an optical imaging platform that can track immunomarkers with spatiotemporal control but also demonstrates an externally controlled light-triggered therapeutic approach enabling receptor-specific treatment with biocompatible theranostic nanoprobes.

Localization of PD‐L1 on single cancer cells by iSERS microscopy with Au/Au core/satellite nanoparticles

“…Overall, the presented false‐color images in Figure demonstrate the capability of iSERS for selectively localizing PD‐L1 on single SkBr‐3 cells. The presented results confirm earlier iSERS PD‐L1 results on MDA‐MB‐231 cells .…”

“…A promising alternative to IHC and IF is immuno‐SERS microscopy (iSERS) . This emerging technique is based on surface‐enhanced Raman scattering (SERS) for optical readout and circumnavigates the problems associated with IHC and IF .…”

PRADA: Portable Reusable Accurate Diagnostics with nanostar Antennas for multiplexed biomarker screening

“…[17][18][19] We have shown that the near-field electromagnetic radiation generated at the protrusions of GNSs gives rise to a > 10 9 enhancement in SERS signal, resulting in ultrasensitive detection in vitro, in vivo, and in biosensors. [20][21][22][23][24] Here, we demonstrated multiplexed detection of two biomarkers of myocardial infarction including cardiac troponin I (cTnI) and neuropeptide Y (NPY) with PRADA with high sensitivity and specificity in patient sera. cTnI is a well-accepted serum biomarker of cardiac arrest, stress, and ischemic stroke.…”

Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

“…NPMBC possess cytotoxic activity per se [39,66,67,69]; however, their main applications are related to their ability to act as radiosensitizers in cancer cells through the induction of G2/M phase cell cycle arrest [36,47,66], as agents for PCT applications [14,28,29,37,63] or as transmembrane carriers for the controlled release and targeted delivery of anticancer drugs increasing their cellular uptake [30,39,40], among others [47,64]. Cancer cells in a tumor are very heterogeneous, that is, they differ in marker expression, morphology, proliferation capacity, growth stage, etc.…”

“…Furthermore, due to the lack of specific molecular targets in this subtype of BC [7], which makes its treatment difficult, chemotherapy remains an essential component for the management of TNBC, both adjuvant and neoadjuvant therapy [8,9]. Besides their diagnostic use [14][15][16][17][18][19][20][21], metallodrugs or metal-based complexes (MBC) stand out for being promising chemotherapeutic agents [22]. The therapeutic potential of MBC has long been known; however, their role in the treatment of cancer is relatively recent (1960s).…”