Gold Nanorods Coated with Apolipoprotein E Protein Corona for Drug Delivery

The endogenously formed protein corona from human serum (HS) proteins on nanoparticles (NPs) has recently been exploited as a carrier for loading and delivery of small molecular therapeutics. However, not all serum corona proteins possess affinity for these therapeutics, which leads to reduced loading efficiency. Here, we enhance the utility of the protein corona by pre-forming a homogeneous protein corona around gold nanorods (NRs) using only apolipoprotein E (ApoE), which exhibits high affinity for both hydrophilic and hydrophobic drugs due to its amphipathic nature, as well as increased uptake by cancer cells overexpressing low-density lipoprotein (LDL) receptors. We loaded a hydrophobic photosensitizer chlorin e6 (Ce6) onto the ApoE corona around NRs, with the resulting NR-ApoE-Ce6 giving a much higher Ce6:NR ratio as compared to the HS corona. NR-ApoE-Ce6 also showed enhanced uptake of Ce6 in Cal 27 oral squamous cell carcinoma (OSCC) cells by up to 58.0% in vitro compared to same concentration of Ce6 alone formulated in ApoE. This resulted in a 27.0% increase in intracellular generation of reactive oxygen species (ROS) on irradiation with a 665 nm continuous wave laser. The combined photothermal therapy (PTT) by NRs and photodynamic therapy (PDT) by Ce6 achieved 96.7% destruction of cancer cells with just 3.33 pM NR-ApoE-Ce6 loaded with 2 μM Ce6, as compared to 78.4% of cell kill with an equivalent 2 μM free Ce6. The appropriate choice of specific proteins to form the protein corona around NPs could thus further improve the therapeutic loading capacity of the corona and consequently its therapeutic efficacy.