Although synergistic effects of
photothermal therapy (PTT) and
chemotherapy for
cancer have been extensively investigated in previous studies, more potential strategies need to be exploited to alleviate severe adverse effects. In this study, a
biotin-modified and activatable nanotheranostic system is developed. This system (BPSP/DOX-CyBA) composed of H2O2-sensitive thioketal (TK) linker, hydrophilic
biotin-decorated
polyethylene glycol (PEG) segment, hydrophobic
polycaprolactone (PCL) segment, could self-assemble into (99 ± 1.3) nm nanoparticles and co-deliver H2O2-triggered
photosensitizer CyBA and cytotoxic drugs DOX to
tumor site. In vitro, DOX and CyBA could release rapidly from nanoparticles, CyBA accumulation in the mitochondria causes mitochondrial damage, leading to
mitochondrial dysfunctions,while rising the level of ROS in B16F10 cells, and further to promote the micells to trigger release. CyBA could be activated into CyOH and the
photothermal therapy was turn "off" into "on". In BPSP/DOX-CyBA group, the local temperature within
tumor reached 50 °C and cell apoptosis rate reached 68.6% under
Laser irradiation (650 nm, 1 W/cm2). Fluorescence microscopy and flow cytometry analysis further demonstrated the better uptake efficiency on B16F10 cells with
biotin decoration. In a mice B16F10
tumor model, the group with co-delivery CyBA and DOX had the best
tumor retention effect, the maximal local temperature increasement and the minimum
tumor growth with negligible side effects, suggesting the potential of BPSP/DOX-CyBA nanopalteform that synergistic
photothermal therapy and
chemotherapy and mitochondria damage as an effective
melanoma treatment strategy.