A novel nanoparticle-based multi-modal phototherapy consisting of gold nanorods (AuNRs) co-loaded with the photosensitizer Chlorin e6 (Ce6), and chemotherapeutic agent Doxorubicin (Dox) within a pre-formed human serum (HS) protein corona, i.e. AuNR-HS-Ce6-Dox, was synthesized in order to perform simultaneous photothermal (PTT), photodynamic (PDT) and chemotherapy (CTX) under single laser irradiation at a wavelength of 665nm.
The excitation of AuNRs and Ce6 resulted in photothermal ablation (PTT) and production of reactive oxygen species (ROS) to elicit oxidative stress (PDT) in Cal 27 oral squamous cell carcinoma (OSCC) cells, while laser-triggered Dox release and subsequent DNA intercalation resulted in additional DNA damage (CTX) – eventually resulting in cell death.
High laser-triggered Dox release efficiency of 71.5 % as well as strong AuNR plasmonic enhancement of ROS production – as verified with 3’-(p-aminophenyl) fluorescein (APF) – by loaded Ce6 (11.7-fold increase as compared to free Ce6) was observed. Uptake of both Ce6 and Dox co-loaded on AuNRs by Cal 27 cells was also greatly enhanced, as demonstrated using flow cytometry and confocal laser scanning microscopy (CLSM), with 3.3 and 52 times higher intracellular Dox and Ce6 uptake fluorescence observed respectively after a 6 h dose of AuNR-HS-Ce6-Dox as compared to the use of free Ce6/Dox.
The simultaneous laser-triggered tri-modal therapy also achieved a near complete eradication of cancer cells (98.7% cell death) with an extremely low dose of AuNR-HS-Ce6-Dox (15pM AuNR loaded with 1.26 nM Ce6 and 12.5 nM Dox), and low dark toxicity was observed. Additionally, the loaded drug concentrations were far lower than any previously reported in vitro, thereby greatly minimizing potential systemic toxicity of these agents. Finally, enhanced treatment efficacy was attributed to strong synergistic enhancement between therapies, as compared to individual therapies performed separately.
Targeted drug delivery and nanocarriers , Nanomedicine for cancer diagnosis & therapy
