NIR-Sensitive Au-Au2S Nanoparticles for Targeted Drug Delivery

 

The invasive nature and adverse side effects of surgery and chemotherapy have limited the efficacy of cancer treatment. Our laboratory has incorporated tissue penetrating near infrared (NIR) light and NIR-sensitive nanoparticles to develop a minimally invasive drug delivery system. NIR-activated release of an anticancer drug from NIR-sensitive nanoparticles could potentially reduce deleterious side effects and allow treatment of surgically inoperable tumors.

The NIR-sensitive nanoparticles employed for targeted drug delivery system in our work were synthesized by reduction of tetrachloroauric acid (HAuCl4) using sodium sulfide (Na2S).  In contrast to organic particles, inorganic nanoparticles potentially offer increased flexibility in manipulation of optical properties.  The properties of inorganic nanoparticles may be tailored by controlling the size, surface, shape and domain interactions.  The as-synthesized NIR-sensitive nanoparticles exhibited two absorption bands at wavelength, l of about 530 nm and NIR absorption between l = 650 – 1100 nm as shown in Figure 1.  The as-synthesized nanoparticles were composites of crystalline gold (Au) and amorphous gold sulfide (Au2S).  The NIR absorption was unique to as-synthesized nanoparticles, and was absent in either Au or Au2S nanoparticles.  There was no evidence that NIR absorption properties were related to a core-shell structure as suggested in earlier work in the literature.  In addition, the effects of concentration ratios for precursors used in the chemical synthesis of nanoparticles were correlated with the resultant NIR properties.  Consequently, by varying concentration ratios of precursors, the optical properties of as-synthesized nanoparticles were tailored.  This ability to tailor optical properties would further advance the potential use of as-synthesized nanoparticles for optically-activated drug delivery systems or other biomedical applications.

Functionalization of NIR-sensitive Au-Au2S nanoparticles with surfactants has facilitated the loading of anticancer drugs as shown in Figure 2.  Surfactants of different hydrocarbon chain lengths were used to modify the nanoparticles, and subsequently altered interfacial interactions between nanoparticles and surfactants.  The loading of anticancer drugs governed by surfactant interfacial interactions was correlated to the surfactant chain length.  In addition, inorganic-organic interfacial interactions between nanoparticles and surfactants may be used to manipulate the optical properties of NIR sensitive drug delivery system.  Drug release was triggered upon NIR laser irradiation using a Nd:YAG pulse laser at l = 1064 nm.  The structural and microstructural changes of Au-Au2S nanoparticles upon NIR laser irradiation were studied.  Insights to NIR triggered drug release process were elucidated from the estimated magnitude of thermal effects and structural and microstructural changes induced by NIR irradiation.

In addition, the in vitro cytotoxicity of the NIR-sensitive Au-Au2S drug delivery system was assessed using breast cancer cells as an essential preliminary safety criterion for its potential clinical application.  The cytotoxicity of surfactant-modified nanoparticles and drug-loaded-surfactant-modified nanoparticles were investigated.  It was found that the toxicity of drug-loaded-surfactant-modified nanoparticles depended on the surfactant used for drug adsorption.  The in vitro cytotoxic effects of released drugs in the supernatant fraction collected after NIR irradiation of drug-loaded-surfactant-modified nanoparticles were evaluated.  The effects induced by NIR irradiation or surface drug loading on the cytotoxicity of released drugs were also ascertained.  It was found that the released drug was chemically modified with increased toxicity.  Besides NIR-sensitive Au-Au2S nanoparticles, other inorganic nanoparticles (NIR-to-visible upconversion nanoparticles and magnetic ferrites) were also investigated for their potential biomedical applications.

Figure 1: Optical properties of NIR-sensitive nanoparticles.

Figure 2: Schematic of NIR-activated targeted drug delivery system.

Principal investigator: Chow Gan Moog

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Tel : 6516 3325