Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B...

Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.

T ₁–T₂ dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T₁–T₂ dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T₁–T₂ dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe₃O₄/Gd₂O₃ nanocubes as T₁–T₂ dual-modal CAs and their application for enhanced T₁–T₂ MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe₃O₄/Gd₂O₃ nanocubes have an r₁ value of 45.24 mM⁻¹ s⁻¹ and an r₂ value of 186.51 mM⁻¹ s⁻¹, which were about two folds of those of Gd₂O₃ nanoparticles and Fe₃O₄ nanocubes, respectively. In vivo MR imaging of rats showed both T₁-positive and T₂-negative contrast enhancements in the livers. We envision that our Fe₃O₄/Gd₂O₃ nanocubes could be applied as T₁–T₂ dual modal MR CAs for a wide range of theranostic applications in the near future.