Poly-(allylamine hydrochloride)-coated but not poly(acrylic acid)-coated upconversion nanoparticles induce autophagy and apoptosis in human blood cancer cells

Abstract

Upconversion nanoparticles (UCNPs) have gained increased attention due to their various medical applications such as drug delivery, detection, imaging, and photodynamic therapy. But little is known about their direct biological activity. In the present study, we synthesized NaYF₄:Yb,Er UCNPs coated with poly-(allylamine hydrochloride) (PAH) or poly(acrylic acid) (PAA) and investigated their effects in human myeloma and leukemia cells. When these cells were incubated with both types of UCNPs, we found that PAH-UCNPs but not PAA-UCNPs increased the expression of LC3-II, a hallmark of autophagy. This effect was confirmed by the accumulation of LC3 puncta as analyzed by immunofluorescence microscopy. Induction of LC3-II could be blocked by 3-methyl adenosine (3-MA), an autophagy inhibitor. Consistent with this observation, PAH-UCNPs also inhibited both AKT and mTOR activation, the key step in autophagy activation. Further studies demonstrated that PAH-UCNPs also decreased Bcl-2 but increased Beclin1 and Atg14 expression, suggesting that PAH-UCNPs-induced autophagy was associated with increased PI3KC3–Beclin1 activity. Moreover, PAH-UCNPs induced apoptosis in myeloma cells and enhanced apoptosis induced by bortezomib and doxorubicin, two major anti-myeloma drugs. Therefore, our study suggested that PAH-UCNPs alone can induce both apoptosis and autophagy in human blood cancer cells by modulating the AKT–mTOR and PI3KC3–Beclin1–Atg14 signaling pathways. This study implies the potential application of PAH-UCNPs in blood cancer-cell killing.