Acridine orange tethered chitosan reduced gold nanoparticles: a dual functional probe for combined photodynamic and photothermal therapy

Abstract

Plasmonic nanoparticles have been widely used in photomedicine owing to their unique photophysical properties including surface plasmon resonance, high optical extinction and extensive thermal stability, which makes metal nanoparticles more suitable for application in cancer phototherapy. Here, we exploit the appropriateness of chitosan reduced gold nanoparticles (AuNPs) as a photothermal converter, photodynamic carrier and contrast agent in the applications of bioimaging, photothermal (PTT) and photodynamic therapy (PDT), concurrently to destroy the human breast cancer cells (MCF-7). AuNPs were successfully conjugated by non-covalent interaction with hydrophilic photosensitizer, acridine orange (AO) through glutathione (GSH) to achieve improved PDT and PTT therapy. This could be attributed to the high loading efficiency with enhanced cellular uptake and excellent photothermal stability of the nanoconjugate (AO@GSH-AuNPs). In addition, the anticancer activity of the nanoconjugate in combination with blue light irradiation (l ¼ 492 nm) demonstrated a pronounced effect compared to the free AO or light irradiation. Thus results of our studies represent the dual mode action of both AO and AuNPs showing photodynamic and photothermal ablation, respectively. Our findings suggest that the AO@GSH-AuNPs nanoconjugate could be used as a multifunctional probe for anticancer therapy.

Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer

“…25 Hari et al developed waterstable 14 nm chitosan reduced AuNPs functionalised with glutathione, which was electrostatically bound to the photosensitiser acridine orange. 26 The high loading of photosensitiser yielded highly fluorescent AuNPs conjugates with an enhanced PDT effect in vitro. The irradiation at 492 nm induced not only the production of singlet oxygen via activation of the acridine orange, but it was also reported that an increase in temperature was induced with the AuNPs acting as the photothermal agents.…”

“…The selected linkers include multidentate passivant ligands, 23 cysteine, 24 thiourea, 25 glutathione, 26 lipoic acid, 27 and imidazole containing linkers. 28 The use of multidentate passivant ligands for the conjugation of a porphyrin to AuNPs was explored by Ohyama et al.…”

“…Therefore, it was suggested that this nanoplatform can be used for a dual PDT/PTT therapy. 26 The Pérez-García group has developed several nanoplatforms with non-conventional linkers for the conjugation of photosensitisers for PDT. 27,28 The group studied the photodynamic effect of three gold-based nanoplatforms, differing in size and shape, conjugated to porphyrin photosensitisers via a lipoic acid linker.…”

Gold Nanoparticle Mediated Phototherapy for Cancer

“…Subsequently, they demonstrated that both gold nanoparticles and gold nanorods conjugated with indocyanine green could accomplish dual-modality PDT and PTT [127]. Other groups also demonstrated the synergistic influence of hyperthermia on PDT with different light, different photosensitizer, different gold nanostructure, and different cell lines [128][129][130][131]. Differently, Gao et al synthesized a new nanostructure using lipid-loaded hypocrellin B (HB) to coated gold nanocages.…”

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

“…This indicates that a single 15 min treatment is sufficient to realize the effects of PDT and a longer exposure time does not necessarily increase the efficacy. Studies evaluating the effect of concentration of AO on its cytotoxic effects have found saturation in the killing efficiency with increasing concentration and comparable output for free and conjugated AO . Our results augment these studies and suggest that increase in either concentration or time of treatment does not necessarily result in higher cytotoxic outcome.…”