Photothermal release of an encapsulated therapeutic agent from polymer-wrapped gold nanoparticles

Abstract

Visible light is used to generate heat from gold nanoparticles wrapped in an amphiphilic polymer shell and trigger a reverse Diels-Alder reaction of a 'caged' tyrphostin therapeutic agent. The hydrophilic nature of the released agent results in it travelling from the polymer to the bulk medium, while the byproduct of the reaction is trapped in the hydrophobic layer of the nano-assembly.

Fig. 1. Left ‘cell’: bicyclic compound 1 encapsulated within the hydrophobic shell surrounding the octadecylamine-coated gold nanoparticles. Middle ‘cell’: the retro-Diels–Alder reaction of bicyclic compound 1 releasing tyrphostin A8 (T8) and the diene. Right ‘cell’: release of T8 into the bulk aqueous environment and retention of 1-methoxy-1,3-cyclohexadiene within the hydrophobic layer of the nano-assembly.

Scheme 1. Synthesis of bicyclic compound 1 from tyrphostin A8 (T8) (top) and wrapping and encapsulation of the nano-assemble NP-P-1 (bottom).

Fig. 2. (a) Normalized UV-vis absorption spectra of dispersions of citrate-coated gold nanoparticles AuNP (NP citrate) in water (2.55 mg mL⁻¹) (black line), ODA-coated gold nanoparticles (NP ODA) in chloroform (0.39 mg mL⁻¹) (blue line), and NP-P-1 in water (2.66 μg μL⁻¹) (red line). (b) TEM image of the final nano-assemblies NP-P-1.

Fig. 3. (a) Changes in the UV-vis absorption spectrum when a 4.1 mM 40% aqueous DMSO solution of 1 is heated at 90 °C for 3 hours. (b) Changes in absorption intensities at 415 nm and 330 nm corresponding to T8 and p-hydroxybenzaldehyde, respectively. (c) Changes in the UV-vis absorption spectrum when 40% aqueous DMSO solutions of T8 (top) and p-hydroxybenzaldehyde (bottom) are heated at 50 °C for 5 minutes. (d) Changes in absorption intensities at 353 nm and 430 nm for T8 (top) and 285 nm and 337 for p-hydroxybenzaldehyde (bottom).

Scheme 2. Retro-Diels–Alder reaction of bicyclic compound 1 and subsequent hydrolysis to 4-hydroxybenzaldehyde.

Fig. 4. (a) Changes in the UV-vis absorption spectrum when an aqueous solution of NP-P-1 (2.66 μg μL⁻¹) is irradiated with a nanosecond pulse laser (10 ns, 532 nm) at 800 mW cm⁻². The red line corresponds to released T8 in the supernatant after centrifugation. (b) The difference spectra of the same data clearly showing the growth of an absorption band at 412 corresponding to the released T8 and a slight blue-shift of the SPR band of the nanoparticle.