Recent Advances in Gold Nanoformulations for Cancer Therapy

Shevtsov, Maxim; Zhou, Yang; Khachatryan, W. А.; Multhoff, Gabriele

doi:10.2174/1389200219666180611080736

Cited by 23 publications

(10 citation statements)

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“…In recent years, research on therapies using nanoparticles has gained popularity, with the aim of targeting cancer cells more selectively [28]. Strategies have included the combination of antibody and GNP conjugation increase delivery efficiency, diagnostic accuracy, and exert anticancer effects using lasers of specific wavelengths [27,[29][30][31][32]. In the present study, NTP combined with Ab-conjugated GNP were used with an aim of increasing the targeting efficiency and enhancing cell death.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

et al. 2021

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Combination therapies for the treatment of oral squamous cell carcinoma have been studied extensively and represent a synergistic approach with better outcomes than monotherapy. In this study, a novel combination therapy was investigated using gold nanoparticles (GNP) conjugated to programmed cell death protein ligand 1 (PD-L1) antibodies and nonthermal plasma (NTP). The present study describes the effectiveness of NTP using PD-L1 antibody conjugated to GNP in PD-L1 expressing SCC-25 cells, an oral squamous cell carcinoma line. Immunocytochemistry revealed higher levels of PD-L1 expression and an increase in the selective uptake of PD-L1 antibody + GNP on SCC-25 cells compared to HaCaT cells. In addition, cell viability analyses confirmed higher levels of cell death of SCC-25 cells after treatment with PD-L1 antibody, GNP, and NTP compared to HaCaT cells. Among the experimental groups, the highest cell death was observed upon treatment with PD-L1 antibody + GNP + NTP. Following the Western blot analysis and immunofluorescence staining, the expression of apoptosis-related proteins was found to increase after treatment with PD-L1 antibody + GNP + NTP among the other experimental groups. In conclusion, the treatment of SCC-25 cells with PD-L1 antibody + GNP + NTP significantly increased the number of dead cells compared to other experimental groups. The results of this in vitro study confirmed the therapeutic effects of PD-L1 antibody + GNP + NTP treatment on oral squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

et al. 2021

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“…The application of AuNPs for imaging in vivo is a promising new approach in the field of in vivo imaging [7,23,24]. The uptake of antibody-conjugated nanoparticles into tumor cells is dependent on several factors: the expression density of receptors, which are expressed on the target cells; the distribution of the target epitopes throughout the cells [25]; the affinity of the tracer to the membrane epitope; and the speed of internalization [21,26].…”

Section: Discussionmentioning

confidence: 99%

“…Biocompatible camouflage of the NP surface is a prerequisite to avoid immediate uptake by macrophages. Small AuNPs (<100 nm) demonstrated to be beneficial for utilization in clinical applications [5][6][7]. Apart from the formulation of AuNPs, tumor imaging with nanoparticle-based contrast agents can be further improved and specified by functionalization with antibodies targeting tumor-specific, membrane-bound biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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

Kimm

Shevtsov

Werner

et al. 2020

Cancers

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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.

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“…The application of gold nanoparticles for imaging in vivo is a promising new approach in the field of in vivo imaging [6,18,19]. The uptake of antibody-conjugated nanoparticles into tumor cells is dependent on different factors.…”

Section: Discussionmentioning

confidence: 99%

“…Biocompatible camouflage of the NP surface is a prerequisite to avoid immediate and quantitative uptake by macrophages. Small nanosized gold particles ( 100nm) demonstrated to be beneficial for utilization in clinical applications [4][5][6]. Apart from the formulation of the NPs, tumor imaging with nanoparticle-based contrast agents can be further improved and specified by functionalization with antibodies targeting tumor-specific, membrane-associated biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle Mediated Multi-Modal CT Imaging of 3 Hsp70 Membrane Positive Tumors

Kimm¹,

Shevtsov²,

Werner³

et al. 2020

Preprint

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Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. 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 functionalized gold nanoparticles (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 tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

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Recent Advances in Gold Nanoformulations for Cancer Therapy

Abstract: Synthetic development of gold nanoformulations became an important strategy in nanomedicine. Nanocomplexes demonstrated a therapeutic potential and could be translated into clinical strategies for cancer therapy.

Cited by 23 publications

References 0 publications

Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

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

Gold Nanoparticle Mediated Multi-Modal CT Imaging of 3 Hsp70 Membrane Positive Tumors

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