Surface modification of gold nanoparticles with 6-mercapto-1-hexanol to facilitate dual conjugation of protoporphyrin IX and folic acid for improving the targeted photochemical internalization

Armin Imanparast; Neda Attaran; Hossein Eshghi; Ameneh Sazgarnia

doi:10.22038/IJBMS.2022.63622.14033

Surface modification of gold nanoparticles with 6-mercapto-1-hexanol to facilitate dual conjugation of protoporphyrin IX and folic acid for improving the targeted photochemical internalization

Iran J Basic Med Sci. 2022 Aug;25(8):970-979. doi: 10.22038/IJBMS.2022.63622.14033.

Authors

Armin Imanparast¹, Neda Attaran², Hossein Eshghi³, Ameneh Sazgarnia¹

Affiliations

¹ Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Medical Nanotechnology, Applied Biophotonics Research Center, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran.
³ Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Abstract

Objectives: Photochemical internalization (PCI) is an important type of photodynamic therapy for delivering macromolecules into the cytosol by the endocytosis process. In this study, 6-mercapto-1-hexanol (MH) was used to functionalize the gold nanostructure as a primer for surface modification to improve conjugation of multi-agents such as protoporphyrin IX (Pp-IX) and folic acid with gold nanoparticles (PpIX/FA-MH-AuNP) to facilitate the photochemical internalization.

Materials and methods: After surface modification of AuNPs with MH, PpIX and FA are bonded to the surface of the MH-AuNPs through the coupling reaction to produce the desired conjugated AuNPs. In the next step, the synthesized nanostructures were characterized by different methods. Finally, after selecting specific concentrations, light treatments were applied and cell survival was measured based on MTT analysis. Also, in order to better study the morphology of the cells, they were stained by the Giemsa method. The SPSS 16 software was used for data analysis.

Results: By surface modification of the nanostructure with MH and then conjugation of FA to it, the incubation time of the drug in PpIX/FA-MH-AuNP was reduced from 3 hr to 30 min. Also, at each light dose, cell death in the presence of PpIX/FA-MH-AuNP was significantly reduced compared with unconjugated conditions (P<0.001). Under these conditions, the ED50 for PpIX and PpIX-MH-AuNP and PpIX/FA-MH-AuNP at a concentration of 2.5 μg/ml is 8.9, 9.1, and 6.17 min, respectively.

Conclusion: The results show that the PCI of PpIX/FA-MH-AuNP increases the selective phototoxicity efficiency on cancer cells compared with the conventional process of photodynamic therapy.

Keywords: 6-mercapto-1-hexanol; Cervical cancer; Folic acid; Gold nanoparticle; Photochemical – internalization; Photodynamic therapy; Protoporphyrin-IX.