4 research outputs found
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
General and Facile Coating of Single Cells via Mild Reduction
Cell surface modification has been
extensively studied to enhance
the efficacy of cell therapy. Still, general accessibility and versatility
are remaining challenges to meet the increasing demand for cell-based
therapy. Herein, we present a facile and universal cell surface modification
method that involves mild reduction of disulfide bonds in cell membrane
protein to thiol groups. The reduced cells are successfully coated
with biomolecules, polymers, and nanoparticles for an assortment of
applications, including rapid cell assembly, in vivo cell monitoring,
and localized cell-based drug delivery. No adverse effect on cellular
morphology, viability, proliferation, and metabolism is observed.
Furthermore, simultaneous coating with polyethylene glycol and dexamethasone-loaded
nanoparticles facilitates enhanced cellular activities in mice, overcoming
immune rejection
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