Exploring the Steric and Electronic Factors Governing the Regio- and Enantioselectivity of the Pd-Catalyzed Decarboxylative Generation and Allylation of 2‑Azaallyl Anions

The impact of the steric and electronic factors in both the <i>para</i>-substituted benzaldimine and 2,2-diarylglycine components on the regioselectivity and enantioselectivity of the palladium-catalyzed decarboxylative allylation of allyl 2,2-diarylglycinate aryl imines was explored. These studies revealed that using 2,2-di­(2-methoxyphenyl)­glycine as the amino acid linchpin allowed for the exclusive synthesis of the desired homoallylic benzophenone imine regioisomers, independent of the nature of the imine moiety, in typically high yields. The resulting enantiomeric ratios, however, are slightly decreased in comparison to the transformations involving the corresponding allyl 2,2-diphenylglycinate imines, but this is more than balanced out by the increases in yield and regioselectivity. Overall, these studies suggest a general strategy for the highly regioselective functionalization of 2-azaallyl anions

Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents

Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents

Renal-Clearable Hollow Bismuth Subcarbonate Nanotubes for Tumor Targeted Computed Tomography Imaging and Chemoradiotherapy

Although metallic nanomaterials with high X-ray attenuation coefficients have been widely used as X-ray computed tomography (CT) contrast agents, their intrinsically poor biodegradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance <i>in vivo</i>. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy. The BNTs could be targeted to tumors with high efficiency and exhibit a high CT contrast effect. Moreover, simultaneous radio- and chemotherapy using drug-loaded BNTs could significantly suppress tumor volumes, highlighting their potential application in CT imaging-guided therapy. Importantly, the elongated nanotubes could be disassembled into isolated small nanoclusters in the acidic tumor microenvironment, accelerating the payload release and kidney excretion. Such body clearable CT contrast agent with high imaging performance and multiple therapeutic functions shall have a substantial potential for biomedical applications

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma

Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC