Exploiting the protein corona around gold nanorods for low-dose combined photothermal and photodynamic therapy.

A nanodevice comprising human serum (HS) protein corona coated gold nanorods (NRs) has been developed to perform both photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously at a very low dose under irradiation by a single laser. Here, we exploit the protein corona to load a photosensitizer, chlorin e6 (Ce6), to form NR-HS-Ce6, whose excitation wavelength matches with the longitudinal surface plasmon resonance (LSPR) of NRs. When excited by a single laser, the NRs caused photothermal ablation of cancer cells while Ce6 simultaneously produced reactive oxygen species (ROS) to kill cancer cells through oxidative stress in PDT. We found that the protein corona did not affect the photothermal heating of NRs and observed more than 5-fold increase in ROS generation when Ce6 was loaded on NR-HS compared to free HS-Ce6 dissolved in HS. The uptake of Ce6 by Cal 27 oral squamous cell carcinoma (OSCC) cells also increased 57-fold when loaded on NR-HS compared to free HS-Ce6. While both PDT and PTT have established modest success in reducing cancer cell viability on their own, we have shown that the combined therapy can achieve near complete eradication (95.2% cell kill) of cancer cells even at an extremely low dose of 50 pM of NR-HS-Ce6 containing an equivalent of 7.67 μg mL Au and 4.83 nM Ce6. This near complete cell kill at such a low dose has not been reported previously. The advantages of this nanoscale delivery system showcase the application of protein corona in cancer treatment instead of considering it as an undesirable biological artefact.