Collagen-induced assembly of adenosine monophosphate-modified gold nanoparticles for photothermal cancer therapy

Abstract

BackgroundPhotothermal therapy (PTT) has become an attractive approach for cancer treatment due to its merits of minimal invasiveness, location selectivity, and suitability for various cancer types. In PTT, photosensitizers are usually adopted to convert light to heat at tumor site, thereby generating heat-induced necroptosis or apoptosis. Therefore, the performance of photosensitizer (e.g., photothermal conversion efficiency (PCE), surface property, tumor accumulation and retention, etc.) determines the clinical manifestation of PTT. Currently, the poor tumor retention and potential long-term toxicity are two main obstacles for developing efficient photosensitizers. To address these issues, we have developed an in vivo tumor microenvironment stimuli-responsive self-assembled photosensitizer, which consists of a biomolecule, adenosine monophosphate (AMP) modified gold nanoparticles (AAu NPs), to enhance the accumulation and retention within tumor tissue for efficient PTT.ResultsThe obtained AAu NPs with a hydrodynamic diameter of 9.12 ± 0.82 nm have excellent colloidal stability in aqueous solution. No sediments can be observed in the AAu NPs aqueous phase even after several months. The temperature of AAu aqueous suspension is elevated to 53.0 ℃ within 8 min at a low particle concentration of 80 μg/mL. A high PCE of 62.8% is obtained for AAu NPs based on the temperature change curves. The near-infrared (NIR) absorption and PCE of AAu NPs are enhanced compared to the surfactant-free Au NPs, enabling excellent photothermal cell-killing in vitro. When the AAu NPs arrive at the tumor tissue, they quickly form large aggregates via a collagen-induced assembly, leading to enhanced NIR absorption and improved tumor accumulation and retention, which enables a high PTT efficacy in vivo at a low photosensitizer dose of 40 μg and a low laser power density of 1.91 W/cm2.ConclusionsA collagen-induced self-assembled gold photosensitizer for efficient PTT has been synthesized based on a biomolecule, AMP modification method. The synthesized AAu NPs with high PTT efficacy, superior biosafety and fast excretion from the body is an effective therapeutic agent in photothermal cancer therapy.