Background
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.
Results
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.
Conclusion
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.
Graphical Abstract
This research describes the development of a new design of electrospun nanosorbent, polystyrene/methacrylic acid nanofibers (PS/MAA NFs), for the extraction and preconcentration of Methyl green (MG) from aqueous samples via solid phase extraction (SPE). The experimental parameters affecting the SPE extraction efficiency including sample flow rate through the sorbent, ionic strength and pH of the sample solution, weight of sorbent, volume and type of eluent were investigated, and optimized. Under the optimum conditions (40 ml of 1 mg/L MG, pH: 5, sample flow rate: 2 ml/min, 0.1 g PS/MAA NFs and eluting solvent: 3 ml MeOH), the calibration curve was linear in the MG concentration range of 25–1,000 μg/L. The limit of detection and enhancement factor of the proposed method, for extraction from 40 ml sample solution, were obtained as 10 μg/L and 8.3, respectively. MG dye was extracted from different real samples (urban, mineral and river waters) using the proposed adsorbent and the results showed that PS/MAA NFs were suitable for preconcentration and determination of trace amount of methyl green in wastewater samples.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.