Page 41 - TPIS2022

Lecture title:

Tumor Targeting Gold Nanoparticles for Theranostic Applications

ABSTRACT:

Inhibition of tumor angiogenesis through simultaneous targeting of vascular endothelial
growth factor receptor (VEGFR)-1 and -2 is highly efficacious. An antagonist peptide of
VEGFA/VEGFB, referred to as VGB3, can recognize and neutralize both VEGFR1 and
VEGFR2 on the endothelial and tumoral cells, thereby inhibits angiogenesis and tumor
growth. However, improved efficacy and extending injection intervals is required for its
clinical translation. Given that gold nanoparticles (GNPs) can enhance the efficacy of
biotherapeutics, we conjugated VGB3 to GNPs to enhance its efficacy and extends the
intervals between treatments without adverse effects. GNP-VGB3 bound to VEGFR1 and
VEGFR2 in human umbilical vein endothelial (HUVE) and 4T1 mammary carcinoma
cells. GNP-VGB3 induced cell cycle arrest, ROS overproduction and apoptosis and inhibited
proliferation and migration of endothelial and tumor cells more effectively than
unconjugated VGB3 or GNP. In a murine 4T1 mammary carcinoma tumor model,
GNP-VGB3 more strongly than VGB3 and GNP inhibited tumor growth and metastasis, and
increased animal survival without causing weight loss. The superior antitumor effects were
associated with durable targeting of VEGFR1 and VEGFR2, thereby inhibiting signaling
pathways of proliferation, migration, differentiation, epithelial-to-mesenchymal transition,
and survival in tumor tissues. MicroCT imaging and inductively coupled plasma mass
spectrometry showed that GNP-VGB3 specifically target tumors and exhibit greater
accumulation within tumors than the free GNPs. Conjugation to GNPs not only improved
the efficacy of VGB3 peptide but also extended the intervals between treatments without
adverse effects. These results suggest that GNP-VGB3 is a promising candidate for clinical
translation.
Keywords: Gold nanoparticles, Peptide, VEGFR1, VEGFR2, Tumor growth, Signaling pathways

5 International TPCF Preclinical Imaging Symposium (2022) 41
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