Gold-based nanoparticles realize photothermal and photodynamic synergistic treatment of liver cancer and improve the anaerobic tumor microenvironment under near-infrared light

Abstract

In order to solve the different pains caused by traditional cancer treatment methods such as surgical treatment, the nano-drug delivery system provides new ideas for cancer treatment. In this paper, a novel anti-tumor therapy nanoparticle, P(AAm-co-AN)-AuNRs@CeO2-Ce6(PA/Ce6), is prepared, which provides a novel idea for liver cancer treatment. The CeO2-coated gold nanorods were grafted onto the surface of the temperature-sensitive polymer P(AAm-co-AN)-CTPD. The photosensitizer Ce6 is loaded on the surface of the nanoparticles and the polymer layer. CeO2 can effectively alleviate the tumor anaerobic microenvironment, and under 808 nm near-infrared (NIR) excitation, the gold nanorods achieve photothermal conversion to induce local heating, which leads to the phase transition of the polymer layer and realizes a controllable release mechanism. In addition, 660 nm NIR light can effectively induce Ce6 to produce singlet oxygen, thereby effectively killing cancer cells. Under the 808 nm laser irradiation within 600 s, the PA/Ce6 solution can heat up to about 60°C, which was enough to ablate both cancer cells and tumor tissues. When the temperature was 50°C, the cumulative release rate of Ce6 was 95.31%. Under the 808 nm laser irradiation, oxygen production capacity of PA/Ce6 was higher and can effectively reduce the content of hydrogen peroxide in cancer cells. Compared to free Ce6, the reactive oxygen species-mediated fluorescence of PA/Ce6 nanoparticles was greater. The cell viability and migration of HepG2 cells were decreased after the 660 and 880 nm lasers were irradiated at the same time. The cancer cells were further inhibited, showing a good in vitro anti-tumor effect. PA-DOX showed the best tumor growth inhibitory effect under NIR laser irradiation and had no acute toxicity in vivo. Due to the existence of AuNRs, nanoparticles had high-efficiency photothermal conversion ability to achieve photothermal therapy. Ce6 can generate singlet oxygen under the excitation of 660 nm laser to realize photodynamic therapy. The experimental results also showed that PA/Ce6 can effectively decompose hydrogen peroxide under laser irradiation, aiming to effectively alleviate the anaerobic microenvironment of tumors. These indicate that PA/Ce6 plays a promising role for hepatocellular carcinoma treatment.

Synergistic Nanomedicine: Photodynamic, Photothermal and Photoimmune Therapy in Hepatocellular Carcinoma: Fulfilling the Myth of Prometheus?

“…Li, B. et al, designed the nanoparticle P(AAm-co-AN)-AuNRs@CeO 2 -Ce6(PA/Ce6) by grafting cerium dioxide (CeO 2 )-coated gold nanorods onto the surface of the temperaturesensitive polymer P(AAm-co-AN)-CTPD, and then loading the photosensitizer Ce6 onto the surface of the nanoparticles and the polymer layer, for a new modality of antitumor treatment [134]. The in vitro antitumor effect was demonstrated on the one hand by reducing the viability of HepG2 cells treated with nanoparticles and irradiation with a 660 nm laser, through which the photosensitizer Ce6 generated singlet oxygen; and on the other hand, the gold nanorods under the action of 880 nm laser irradiation succeeded photothermal conversion and induced local heating, which led to the phase transition of the polymer layer and achieved a well-controlled release mechanism.…”

“…Simultaneous irradiation with red and NIR lasers destroyed the viability and motility of HepG2 cells, producing a strong antitumor effect in vitro. It was proved that PA/Ce6 could successfully decompose hydrogen peroxide under laser irradiation and effectively attenuate the anaerobic TME, opening up favorable future perspectives and avenues for the management of HCC by synergistic PTT and PDT [134].…”

Zinc phthalocyanine loaded- antibody functionalized nanoparticles enhance photodynamic therapy in monolayer (2-D) and multicellular tumour spheroid (3-D) cell cultures

“…These NP nanocarrier platforms for delivering photosensitizers encompass a numerous range of materials including gold nanoparticles (AuNPs), as reported in previous studies ( Winifred Nompumelelo Simelane and Abrahamse, 2021 ; Li et al, 2022 ; Sarkis et al, 2023 ). AuNPs exhibit distinctive physicochemical properties, characterized by their ability to readily form thiol and amine bonds, and their possession of an inherent surface plasmon resonance (SPR) ( Li et al, 2022 ). These distinct characteristics endow them with remarkable versatility that enable for their precise tuning to align with specific wavelengths of visible or infrared light in PDT applications ( Li et al, 2022 ; Hammami et al, 2021 ).…”

“…AuNPs exhibit distinctive physicochemical properties, characterized by their ability to readily form thiol and amine bonds, and their possession of an inherent surface plasmon resonance (SPR) ( Li et al, 2022 ). These distinct characteristics endow them with remarkable versatility that enable for their precise tuning to align with specific wavelengths of visible or infrared light in PDT applications ( Li et al, 2022 ; Hammami et al, 2021 ). Furthermore, AuNPs exhibit biocompatibility, primarily due to the inert nature of their core, making them relatively non-toxic to cells ( Hammami et al, 2021 ).…”

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

“…Gold nanoparticles have been thoroughly studied as a drug delivery system for RNA/DNA [ 31 ], chemotherapeutics [ 32 , 33 ], and bioimaging [ 34 , 35 ]. Moreover, the intrinsic plasmonic properties of gold nanoparticles have permitted their exploitation as photothermal and photodynamic agents [ 36 , 37 ]. In the presence of external photo-activating light and a photosensitizer, gold nanoparticles can release heat (photothermal therapy) into the surrounding environment or produce large amounts of reactive oxygen species (photodynamic therapy) due to the surface plasmon resonance, eventually triggering cell apoptosis.…”