Plasmonic control of drug release efficiency in agarose gel loaded with gold nanoparticle assemblies

Abstract

Plasmonic nanoparticles (NPs) are exploited to concentrate light, provide local heating and enhance drug release when coupled to smart polymers. However, the role of NP assembling in these processes is poorly investigated, although their superior performance as nanoheaters has been theoretically predicted since a decade. Here we report on a compound hydrogel (agarose and carbomer 974P) loaded with gold NPs of different configurations. We investigate the dynamics of light-heat conversion in these hybrid plasmonic nanomaterials via a combination of ultrafast pump-probe spectroscopy and hot-electrons dynamical modeling. The photothermal study ascertains the possibility to control the degree of assembling via surface functionalization of the NPs, thus enabling a tuning of the photothermal response of the plasmon-enhanced gel under continuous wave excitation. We exploit these assemblies to enhance photothermal release of drug mimetics with large steric hindrance loaded in the hydrogel. Using compounds with an effective hydrodynamic diameter bigger than the mesh size of the gel matrix, we find that the nanoheaters assemblies enable a two orders of magnitude faster cumulative drug release toward the surrounding environment compared to isolated NPs, under the same experimental conditions. Our results pave the way for a new paradigm of nanoplasmonic control over drug release.

Photo-Induced Drug Release from Polymeric Micelles and Liposomes: Phototriggering Mechanisms in Drug Delivery Systems

“…Recent research conducted by Moretti et al [ 39 ] investigated drug release from a compound hydrogel made of agarose and carbomer 974P and loaded with gold nanoparticles. By utilizing the surface plasmon resonance effect of the gold nanoparticles, those nanoparticles act as nuclei to collect and convert light to heat, enabling thermally-induced drug release from the hydrogel matrix.…”

“…By utilizing the surface plasmon resonance effect of the gold nanoparticles, those nanoparticles act as nuclei to collect and convert light to heat, enabling thermally-induced drug release from the hydrogel matrix. The mechanism of drug release is based on the expansion of the mesh size of the hydrogel matrix due to localized heating, thus creating free space in the gel matrix and allowing the entrapped drug molecules to diffuse from the hydrogel [ 39 ]. The increased release due to the SPR effect was noticeable when a model drug (fluorescein dextran (DEX)) had a larger size than the original mesh size of the hydrogel before irradiation with light.…”

“…The increased release due to the SPR effect was noticeable when a model drug (fluorescein dextran (DEX)) had a larger size than the original mesh size of the hydrogel before irradiation with light. Moretti et al [ 39 ] also studied the effect of surface modification of the gold nanoparticles by attaching PEG molecules to stabilize the particles, thus preventing aggregation, referred to as “isolated particles” in the paper. The release profiles of DEX from PEGylated (isolated) and non-PEGylated (aggregated) gold NPs in hydrogels differed.…”

Can Gold Nanoparticles Improve Delivery Performance of Polymeric Drug-Delivery Systems?

“…Finally, a recent work of the research group of Rossi [5] is based on a hybrid material composed by Au NPs loaded in a hydrogel of agarose and carbomer 974P with the final aim to control the release of therapeutic molecules by using an external UV light. In comparison with the thermo-responsive hydrogels described above, this hydrogel responds in the opposite way: the heat released from Au NPs promotes the relaxation and widening of the hydrogel's mesh.…”

“…For this purpose, hybrid materials formed by the loading of Au NPs inside polymer networks are studied to improve local drug delivery. In this case, the easy injection and confinement of the hydrogel in the site of injury represent the main advantages together with local release of both small and large molecules in response to thermal stimuli [5].…”