Title

Sericin grafted multifunctional curcumin loaded fluorinated graphene oxide nanomedicines with charge switching properties for effective cancer cell targeting

RIS ID

140337

Publication Details

Jahanshahi, M., Kowsari, E., Haddadi-Asl, V., Khoobi, M., Lee, J. H., Kadumudi, F., Talebian, S., Kamaly, N. & Mehrali, M. (2019). Sericin grafted multifunctional curcumin loaded fluorinated graphene oxide nanomedicines with charge switching properties for effective cancer cell targeting. International Journal of Pharmaceutics, 572 118791-1-118791-14.

Abstract

Fluorinated graphene has recently gained much attention for cancer drug delivery, owing to its peculiar properties including high electronegativity difference, magnetic resonance imaging contrast agent, and the photothermal effect. However, the hydrophobic nature of fluorinated graphene greatly hinders its application as a biological material. Herein, a novel green method is reported for synthesis of a pH-sensitive charge-reversal and water-soluble fluorinated graphene oxide, modified with polyethyleneimine anchored to sericin-polypeptide (FPS). This nanocarrier was further loaded with curcumin (Cur), and characterized as a nanocarrier for anti-cancer drug delivery. The synthesized nanocarriers contain two different pH-sensitive amide linkages, which are negatively charged in blood pH (≈7.4) and can prolong circulation times. The amide linkages undergo hydrolysis once they reach the mildly acidic condition (pH≈6.5, corresponding to tumor extracellular matrix), and subsequently once reached the lower acidic condition (pH≈5.5, corresponded to endo/lysosomes microenvironment), the FPS charge can be switched to positive (≈+28 mV), which aids the nuclear release. This nanocarrier was designed to selectively enhance cell internalization and nuclear-targeted delivery of curcumin in HeLa, SkBr3 and PC-3 cancer cells. Moreover, FPS-Cur demonstrated high curcumin loading capacity, prolonged curcumin release and promotion of apoptosis in HeLa, SkBr3 and PC-3 cells. Therefore, with its pH-responsive charge-reversal properties, FPS-Cur would be a promising candidate for chemotherapy of cervical, breast and prostate cancers.

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Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.ijpharm.2019.118791