Tumor-targeting nanoparticles and phototherapies are
the two major
trends in tumor-specific, local cancer therapy with minimal side effects.
Organic photosensitizers (PSs) usually offer effective photodynamic
therapy (PDT) but require enhanced solubility and tumor-targeting,
which may be provided by a nanoparticle. Near-infrared (NIR)-emitting
Ag2S quantum dots may act as a delivery vehicle for the
PS, NIR tracking agent, and as a phototherapy (PTT) agent. A combination
of the two provides luminescent dual-phototherapy agents with tumor-specificity
and image-guided and enhanced cytotoxicity as a result of synergistic
PDT and PTT. In this study, brominated hemicyanine (Hemi-Br), a photosensitizer,
was loaded onto folic acid (FA)-tagged, glutathione (GSH)-coated Ag2S quantum dots (AS-GSH QDs) to provide enhanced phototoxicity
via a photodynamic and mild photothermal effect in folate receptor(+)
cancer cell lines at clinically relevant 640 nm irradiation. Final
particles (AS-GSH-FA/Hemi-Br) had a hydrodynamic size of 75.5 nm,
dual emission at both 705 and 910 nm, and a 93% light-to-heat conversion
efficiency under 640 nm laser irradiation.In vitrocytotoxicity studies were conducted with folate receptor (FR)-positive
HeLa and -negative A549 cell lines to differentiate receptor-mediated
uptake. Enhanced phototoxicity on HeLa cells was observed with AS-GSH-FA/Hemi-Br
compared to free Hemi-Br and AS-GSH-FA QDs due to increased uptake
of the photosensitizer via active targeting and combination therapy,
which is especially visible at the safe dose of single agents. Upon
irradiation with a 640 nm (300 mW, 0.78 W/cm2) laser for
5 min, the viability of the HeLa cells decreased from 64% to 42 and
25% when treated with free Hemi-Br, AS-GSH-FA, and AS-GSH-FA/Hemi-Br,
respectively. Overall, AS-GSH-FA/Hemi-Br provides image-guided enhanced
PDT/PTT, which may be adopted for different FR(+) tumors.