Doxorubicin and anti-PD-L1 antibody conjugated gold nanoparticles for colorectal cancer photo-chemotherapy.

Doxorubicin and anti-PD-L1 antibody conjugated gold nanoparticles for colorectal cancer photo-chemotherapy.

Mol Pharm. 2019 Jan 30;:

Authors: Emami F, Banstola A, Vatanara A, Lee S, Kim JO, Jeong JH, Yook S

Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide, and prognosis and overall survival are known to be significantly correlated with the overexpression of PD-L1. Because combination therapies can significantly improve therapeutic efficacy, we constructed doxorubicin (DOX) conjugated and anti-PD-L1 targeting gold nanoparticles (PD-L1-AuNP-DOX) for the targeted chemo-photothermal therapy of CRC. DOX and anti-PD-L1 antibody were conjugated to α-terminal end group of lipoic-acid polyethylene glycol N-hydroxysuccinimide (LA-PEG-NHS) using an amide linkage, and PD-L1-AuNP-DOX was constructed by linking LA-PEG-DOX, LA-PEG-PD-L1 and short PEG chain on the surface of AuNP using thiol-Au covalent bonds. Physicochemical characterizations and biological studies of PD-L1-AuNP-DOX were performed in the presence of near infrared (NIR) irradiation (biologic studies were conducted using cellular uptake, apoptosis and cell cycle assays in CT-26 cells). PD-L1-AuNP-DOX (40.0 ± 3.1 nm) was successfully constructed and facilitated the efficient intracellular uptake of DOX as evidenced by pronounced apoptotic effects (66.0%) in CT-26 cells. PD-L1-AuNP-DOX treatment plus NIR irradiation significantly and synergistically suppressed the in vitro proliferation of CT-26 cells by increasing apoptosis and cell cycle arrest. The study demonstrates that PD-L1-AuNP-DOX in combination with synergistic targeted chemo-photothermal therapy has a considerable potential for the treatment of localized CRC.

PMID: 30698975 [PubMed - as supplied by publisher]

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