Polyacrylic Acid Functionalized Co_0.85Se Nanoparticles: An Ultrasmall pH-Responsive Nanocarrier for Synergistic Photothermal-Chemo Treatment of Cancer

To surmount the challenges of limited drug penetration and therapeutic resistance in solid tumors, stimuli-responsive nanocarrier-based drug delivery systems (DDSs) with relatively small sizes are inherently favorable for combined treatment of cancerous cells. In this work, poly(acrylic acid) (PAA) functionalized Co 0.85 Se nanoparticles (PAA-Co 0.85 Se NPs) were synthesized through an ambient aqueous precipitating approach for synergistic photothermal-chemo treatment of cancer. The obtained PAA-Co 0.85 Se NPs possess ultrasmall size (8.2 ± 2.6 nm), considerable near-infrared (NIR) light absorption, high photothermal transforming efficiency (45.2%) and low cytotoxicity, all of which are beneficial for localized photothermal ablation of cancer cells. Doxorubicin hydrochloride (DOX·HCl) was then successfully loaded on PAA-Co 0.85 Se NPs with a loading capacity up to 8.3% to form PAA-Co 0.85 Se-DOX composites, which exhibited an exciting acidic pH-responsive drug release property due to the protonation of amino groups in DOX and carboxyl groups in PAA molecules. As expected, when HeLa cells were treated with PAA-Co 0.85 Se-DOX NPs as well as NIR laser irradiation, a significant synergistic cell-killing effect was observed, greatly improving the treatment efficiency. Thus, this work presents novel insight into the design of ultrasmall stimuli-responsive nanocarrier-based DDSs for synergistic photothermal-chemo treatment of cancer cells.