Gold Nanoparticle–Protein Agglomerates as Versatile Nanocarriers for Drug Delivery

Abstract

The fabrication of a versatile nanocarrier based on agglomerated structures of gold nanoparticle (Au NP)-lysozyme (Lyz) in aqueous medium is reported. The carriers exhibit efficient loading capacities for both hydrophilic (doxorubicin) and hydrophobic (pyrene) molecules. The nanocarriers are finally coated with an albumin layer to render them stable and also facilitate their uptake by cancer cells. The interaction between agglomerated structures and the payloads is non-covalent. Cell viability assay in vitro showed that the nanocarriers by themselves are non-cytotoxic, whereas the doxorubicin-loaded ones are cytotoxic, with efficiencies higher than that of the free drug. Transmission electron microscopy and fluorescence microscopy along with flow cytometry analysis confirm the uptake of the drug-loaded nanocarriers by a human cervical cancer HeLa cell line. Field-emission scanning electron microscopy reveals the formation of apoptotic bodies leading to cell death, confirming the release of the payloads from the nanocarriers into the cell. Overall, the findings suggest the fabrication of novel Au NP-protein agglomerate-based nanocarriers with efficient drug-loading and -releasing capabilities, enabling them to act as multimodal drug-delivery vehicles.

Facile preparation of albumin-stabilized gold nanostars for the targeted photothermal ablation of cancer cells

“…25 Benefiting from numerous advantages such as non-toxicity, good biocompatibility, excellent biodegradability, good stability in biological environment, low immunogenicity and the presence of functional groups, 26,27 BSA has been widely used as a stabilizing agent or drug carrier in biomedical fields. [28][29][30] In addition, BSA-coated nanoparticles have been found to be taken up preferentially by cancer cells when compared to normal cells, 25,31,32 which enables their potential application for cancer therapy and diagnosis.…”

Theranostic potential of gold nanoparticle-protein agglomerates

“…94,96 Preliminary results from our laboratory (drug-loaded Au NP-lysozyme agglomerates with d H of ~215 nm) and others indicate that Au NP-protein agglomerates could be utilized for delivering drugs and other therapeutic molecules to the tumor site through passive targeting, as the control over the agglomerate size seems achievable. 20,34,35,84 Our results showed that the size of Au NP-protein agglomerates could be controlled by simply varying the concentration of the concerned protein in the medium during formation of the nanocarrier. 26,34 Nonetheless, future studies in this regard are required in order to have better control over the parameters affecting the overall Au NP-protein agglomerate size.…”

“…25,26,34,35 It has recently been shown that the Au NPs at physiological pH (7.5) could induce aggregation of lysozyme, an important enzyme that catalyzes the hydrolysis of peptidoglycan. 25,36 The…”

“…26,37 As mentioned earlier, with the realization of critical importance of protein aggregation in nanobiotechnology, the Au NP-mediated protein aggregation is expected to unveil potential implications in nanomedicine and theranostics. 25,26,34,35,38 However, in order to fully appreciate the prospect of Au NP-protein agglomerates in therapeutic applications, we need to first unravel the possible mechanism of protein aggregation in presence of Au NPs or vice versa.…”

“…Thus, one of the advantages offered by the Au NP-protein agglomerate-based nanocarrier systems is the prospect of loading hydrophilic as well as hydrophobic drugs -either separately or simultaneously -in the same nanocarrier without further modification. 20,34,35 In addition, the Au NPs -being chemically stable and non-toxic -have already been used as drug delivery vehicle. [77][78][79][80] The other benefits of using Au NPs in drug delivery are the ease of synthesis and considerable control over the size and shapeallowing researchers to tune their SPR band from visible to near infra-red (NIR) region leading to exciting therapeutic implications.…”