Two-photon excitation triggers combined chemo-photothermal therapy via doped carbon nanohybrid dots for effective breast cancer treatment

Remotely triggered drug delivery using nanoparticles is an area of great interest for targeted therapy to fight cancer. In this work, we synthesized photoresponsive nanoparticles to remotely initiate the delivery of doxorubicin (DOX) to 3D cultured human breast cancer cells (MCF-7) via NIR two-photon excitation (TPE) using nitrogen-doped and surface passivated (PEG(200)) carbon nanohybrid dots (CNDs). On-demand drug delivery relies on bio-compatible, photo-responsive nano-carriers with high quantum yields. A facile (5 min synthesis) one-pot hot plate method was used to synthesize functionalized and surface passivated carbon nanohybrid dots (CND-P) having 53% quantum yield (QY). Compared to CNDs prepared from citric acid (CND-C) and citric acid plus urea (CND-N), CND-P had QY enhanced by factors of 12.6 and 4.4, respectively. The up-converted emission intensity of CND-P was strengthened by a factor of 4.5 over that of CND-N from nitrogen doped CNDs for similar test conditions (wavelength, excitation power and concentration). The drug loading capacity of CND-P was measured to be 0.98 w/w with the ability to release DOX via two-photon excitation (TPE). Intense green luminescence was observed under both 360 and 780 nm lasers using single and two-photon excitations. The highly biocompatible CND-P showed 88% cell viability at concentrations as high as 1100 mu g/mL. The combined chemo-and photothermal therapeutic effect of the DOX-loaded CND-P (CND-P@DOX) complex resulted in the death of 78% of the MCF-7 cells compared to 59% with DOX alone.