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...

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.

Rationale: Graphene oxide (GO) based nanomaterials have shown potential for the diagnosis and treatment of amyloid-β (Aβ)-related diseases, mainly on Alzheimer's disease (AD). However, these nanomaterials have limitations. How GO is beneficial to eliminate Aβ burden, and its physiological function in Aβ-related diseases, still needs to be investigated. Moreover, postoperative cognitive dysfunction (POCD) is an Aβ-related common central nervous system complication, however, nanomedicine treatment is lacking.

Liver transplantation is currently the only effective treatment for patients with end-stage liver disease; however, donor liver scarcity is a notable concern. As a result, extensive endeavors have been made to diversify the source of donor livers. For example, the use of a decellularized scaffold in liver engineering has gained considerable attention in recent years. The decellularized scaffold preserves the original orchestral structure and bioactive chemicals of the liver, and has the potential to create a de novo liver that is fit for transplantation after recellularization. The structure of the liver and hepatic extracellular matrix, decellularization, recellularization, and recent developments are discussed in this review. Additionally, the criteria for assessment and major obstacles in using a decellularized scaffold are covered in detail.

Many of the neurodegenerative disorders such as Huntington's disease (HD) are caused by the accumulation of intracytoplasmic aggregate-prone proteins. These toxic protein aggregates are mainly degraded by autophagy, thus elevating the autophagy level to enhance the degradation of these proteins representing an emerging viable approach for the treatment of neurodegenerative diseases. In this report we showed that graphene oxide (GO), an engineered nanomaterial with enormous potential in biomedical applications, effectively enhanced the clearance of mutant huntingtin (Htt), the aggregate-prone protein underlying the pathogenesis of HD. This enhancing effect of GO was autophagy-mediated, as blocking autophagy by chemical inhibitors at either the autophagosome formation stage or the autophagosome–lysosome fusion stage, or more specifically by knocking-down an essential autophagy gene, led to a significant reduction in the ability of GO to elicit Htt degradation. Interestingly, the autophagy induced by GO had the normal capacity to degrade its cargo including LC3-II and Htt, but not p62/SQSTM1 (p62), and was dependent on the activation of class III phosphatidylinositol 3-kinase (PtdIns3K) and MEK/ERK1/2 signaling pathways, without mTOR involvement. GO also increased ubiquitination of Htt, an event necessary for Htt's clearance. Furthermore, ubiquitinated huntingtin protein preferentially binds to GO, and abundant GO was found in autophagosomes and autolysosomes, thus raising the possibility that GO may directly deliver the bound protein to autophagosomes for degradation. Our results revealed a novel biological function of GO and may have implications for developing nanomaterial-based therapeutics for neurodegenerative diseases.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse.