Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer

Abstract

A highly efficient drug vector for photodynamic therapy (PDT) drug delivery was developed by synthesizing PEGylated gold nanoparticle conjugates, which act as a water-soluble and biocompatible "cage" that allows delivery of a hydrophobic drug to its site of PDT action. The dynamics of drug release in vitro in a two-phase solution system and in vivo in cancer-bearing mice indicates that the process of drug delivery is highly efficient, and passive targeting prefers the tumor site. With the Au NP-Pc 4 conjugates, the drug delivery time required for PDT has been greatly reduced to less than 2 h, compared to 2 days for the free drug.

Figure 1

Design of the water-soluble Au NPs as a PDT drug delivery agent, Pc 4 structure, and transmission electron microscopy image of the conjugates.

Figure 2

Absorption and emission spectra (inset) of PEGylated Au NP–Pc 4 conjugates in normal saline (0.9% NaCl, pH 7.2).

Figure 3

Photograph of Au NP dispersions, which aggregated when the concentration of Pc 4 was increased in chloroform. Vial 1 was pure Au NPs as control. From vial 2 to vial 5, the [Pc]/[Au NP] concentration ratios were 20:1, 40:1, 50:1, and 60:1, respectively.

Figure 4

Photodecomposition of DPBF by ¹O₂ after irradiation of methylene blue, Pc 4, and Au NP–Pc 4 conjugates in ethanol (monitoring the maximum absorption of DPBF at 410 nm).

Figure 5

Phase transfer study of the conjugates at room temperature and color photographs of Pc 4 in toluene (1), Au NPs (2), and Au NP–Pc 4 conjugates (3) in normal saline (0.9% NaCl, pH 7.2) phases.

Figure 6

Fluorescence images of a tumor-bearing mouse after being injected with Au NP–Pc 4 conjugates in normal saline (0.9% NaCl, pH 7.2), (a) 1 min, (b) 30 min, and (c) 120 min after intravenous tail injection. Any bright signal is due to Pc 4 fluorescence, without which no fluorescence signals were detected from the mouse. (To reduce autofluorescence, the animal was fed a special diet for more than 2 weeks before the experiment.) Unprecedented delivery efficiency and accumulation rate of the drug in the tumor are monitored via the fluorescence increase in the tumor area (white circle). For comparison, a mouse that got only a Pc 4 formulation without the Au NP vector injected is shown in panel (d). No circulation of the drug in the body or into the tumor was detectable 2 h after injection without the Au NP as drug vector.