Immunomodulatory Magnetic Microspheres for Augmenting Tumor-Specific Infiltration of Natural Killer (NK) Cells

The purpose of this research is to develop magnetic resonance imaging (MRI) visible immunomodulatory microspheres (IMM-MS) for efficient image guided cancer immunotherapy. IMM-MS composed of recombinant interferon gamma (IFN-γ), iron oxide nanocubes (IONC), and biodegradable poly­(lactide-<i>co</i>-glycolide) (PLGA) were successfully prepared via a double-emulsion method. The prepared IMM-MS exhibited a sustained IFN-γ release and highly sensitive MR <i>T</i>₂ contrast effects. Finally, in an orthotopic liver tumor VX2 rabbit model, successful hepatic intra-arterial (IA) transcatheter delivery of IMM-MS to liver tumors was confirmed with MR images. The deposition of IMM-MS significantly increased NK-cell infiltration into the liver tumor site

Regenerative Astaxanthin Extraction from a Single Microalgal (<i>Haematococcus pluvialis</i>) Cell Using a Gold Nano-Scalpel

Milking of microalgae, the process of reusing the biomass for continuous production of target compounds, can strikingly overcome the time and cost constraints associated with biorefinery. This process can significantly improve production efficiency of highly valuable chemicals, for example, astaxanthin (AXT) from Haematococcus pluvialis. Detailed understanding of the biological process of cell survival and AXT reaccumulation after extraction would be of great help for successful milking. Here we report extraction of AXT from a single cell of H. pluvialis through incision of the cell wall by a gold nanoscalpel (Au-NS), which allows single-cell analysis of wound healing and reaccumulation of AXT. Interestingly, upon the Au-NS incision, the cell could reaccumulate AXT at a rate two times faster than the control cells. Efficient extraction as well as minimal cellular damage, keeping cells alive, could be achieved with the optimized shape and dimensions of Au-NS: a well-defined sharp tip, thickness under 300 nm, and 1–3 μm of width. The demonstration of regenerative extraction of AXT at a single cell level hints toward the potential of a milking process for continuous recovery of target compounds from microalgae while keeping the cells alive

Droplet-Guiding Superhydrophobic Arrays of Plasmonic Microposts for Molecular Concentration and Detection

Droplet-guiding superhydrophobic SERS substrates are created by a combinatorial lithographic technique. Photolithography defines the pattern of a micropillar array with a radial density gradient, whereas colloidal lithography features a nanotip array on the top surface of each micropillar. The nanotip array renders the surface superhydrophobic, and the pattern of micropillars endows the radial gradient of the contact angle, enabling the spontaneous droplet migration toward the center of the pattern. Water droplets containing target molecules are guided to the center, and the molecules dissolved in the droplets are concentrated at the surface of the central micropillar during droplet evaporation. Therefore, the molecules can be analyzed at the predefined position by Raman spectra without scanning the entire substrate. At the same time, the SERS-active nanotip array provides high sensitivity of Raman measurement

Droplet-Guiding Superhydrophobic Arrays of Plasmonic Microposts for Molecular Concentration and Detection

Droplet-guiding superhydrophobic SERS substrates are created by a combinatorial lithographic technique. Photolithography defines the pattern of a micropillar array with a radial density gradient, whereas colloidal lithography features a nanotip array on the top surface of each micropillar. The nanotip array renders the surface superhydrophobic, and the pattern of micropillars endows the radial gradient of the contact angle, enabling the spontaneous droplet migration toward the center of the pattern. Water droplets containing target molecules are guided to the center, and the molecules dissolved in the droplets are concentrated at the surface of the central micropillar during droplet evaporation. Therefore, the molecules can be analyzed at the predefined position by Raman spectra without scanning the entire substrate. At the same time, the SERS-active nanotip array provides high sensitivity of Raman measurement

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