Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors

Abstract

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo.

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

“…They can be used for several applications, including delivering different compounds and photothermal or photodynamic therapy [ 136 ]. Recently, AuNPs coated with cmHsp70.1 mAb were shown to enable computed tomography of tumors in a preclinical study [ 137 ].…”

Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling

“…A high-sensitivity benchtop X-ray fluorescence imaging platform for detecting AuNPs inside tumors has been developed and the feasibility of L-shell XRF-based quantitative imaging of AuNPs at concentrations as low as 0.007 mg/cm 3 (7 ppm) in biological tissues and liquid water demonstrated [64]. Recently, cmHsp70.1 mAb conjugated AuNPs have been used in a spectral CT system to image accumulated AuNPs in mouse tumors [69].…”

Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

“…In this context, gold nanoparticles (GNPs) have been investigated as anti-cancer drug cargo carriers, whereby their anti-angiogenic and photothermal properties can be used to potentialize drug action [13,14], and their diffusive nature exploited for multimodal synergistic diagnosis and therapy [15,16]. However, uniform intratumoral distribution of these particles with tumor site-specificity and retained accumulation has not yet been achieved according to some recent pre-clinical studies [17,18].…”