Hierarchical Assembly of Bioactive Amphiphilic Molecule Pairs into Supramolecular Nanofibril Self-Supportive Scaffolds for Stem Cell Differentiation

Molecular design of biomaterials with unique features recapitulating nature’s niche to influence biological activities has been a prolific area of investigation in chemistry and material science. The extracellular matrix (ECM) provides a wealth of bioactive molecules in supporting cell proliferation, migration, and differentiation. The well-patterned fibril and intertwining architecture of the ECM profoundly influences cell behavior and development. Inspired by those features from the ECM, we attempted to integrate essential biological factors from the ECM to design bioactive molecules to construct artificial self-supportive ECM mimics to advance stem cell culture. The synthesized biomimic molecules are able to hierarchically self-assemble into nanofibril hydrogels in physiological buffer driven by cooperative effects of electrostatic interaction, van der Waals forces, and intermolecular hydrogen bonds. In addition, the hydrogel is designed to be degradable during cell culture, generating extra space to facilitate cell migration, expansion, and differentiation. We exploited the bioactive hydrogel as a growth-factor-free scaffold to support and accelerate neural stem cell adhesion, proliferation, and differentiation into functional neurons. Our study is a successful attempt to entirely use bioactive molecules for bottom-up self-assembly of new biomaterials mimicking the ECM to directly impact cell behaviors. Our strategy provides a new avenue in biomaterial design to advance tissue engineering and cell delivery

Gold Nanoparticle-Based Activatable Probe for Sensing Ultralow Levels of Prostate-Specific Antigen

It is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence-activatable probe for sensing ultralow levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly developed probe for PSA was pushed down to 0.032 pg/mL, which is more than 2 orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching–unquenching abilities of the dye–AuNP pairs. The efficiency and robustness of this probe were investigated in patient serum samples, demonstrating the great potential of this probe in real-world applications

Tumor-Specific Formation of Enzyme-Instructed Supramolecular Self-Assemblies as Cancer Theranostics

Despite the effort of developing various nanodelivery systems, most of them suffer from undesired high uptakes by the reticuloendothelial system, such as liver and spleen. Herein we develop an endogenous phosphatase-triggered coassembly strategy to form tumor-specific indocyanine green (ICG)-doped nanofibers (<b>5</b>) for cancer theranostics. Based on coordinated intermolecular interactions, <b>5</b> significantly altered near-infrared absorbance of ICG, which improves the critical photoacoustic and photothermal properties. The phosphatase-instructed coassembly process, as well as its theranostic capability, was successfully conducted at different levels ranging from <i>in vitro</i>, living cell, tissue mimic, to <i>in vivo</i>. Specifically, the tumor uptake of ICG was markedly increased to 15.05 ± 3.78%ID/g, which was 25-fold higher than that of free ICG (0.59 ± 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh <i>T</i>/<i>N</i> ratios (>15) clearly differentiated tumors from the surrounding normal tissue. Complete tumor elimination with high therapeutic accuracy has been successfully achieved upon laser irradiation (0.8 W/cm², 5 min) within 24–48 h postinjection. As the first example, <i>in vivo</i> formation of tumor-specific ICG-doped nanofiber for PTT theranostics owns the immense potential for clinical translation of personalized nanomedicine with targeted drug delivery as well as for cancer theranostics

Nuclear Mapping of Nanodrug Delivery Systems in Dynamic Cellular Environments

Nanoformulations have shown great promise for delivering chemotherapeutics and hold tremendous clinical relevance. However nuclear mapping of the chemodrugs is important to predict the success of the nanoformulation. In this study fluorescence microscopy and a subcellular tracking algorithm were used to map the diffusion of chemotherapeutic drugs in cancer cells. Positively charged nanoparticles efficiently carried the chemodrug across the cell membrane. The algorithm helped map free drug and drug-loaded nanoparticles, revealing a varying nuclear diffusion pattern of the chemotherapeutics in drug-sensitive and -resistant cells in a live dynamic cellular environment. While the drug-sensitive cells showed an exponential uptake of the drug with time, resistant cells showed random and asymmetric drug distribution. Moreover nanoparticles carrying the drug remained in the perinuclear region, while the drug accumulated in the cell nuclei. The tracking approach has enabled us to predict the therapeutic success of different nanoscale formulations of doxorubicin

Supplemental material for Canadian Stroke Best Practice Consensus Statement: <i>Acute Stroke Management during pregnancy</i>

<p>Supplemental material for Canadian Stroke Best Practice Consensus Statement: <i>Acute Stroke Management during pregnancy</i> by Noor Niyar N Ladhani, Richard H Swartz, Norine Foley, Kara Nerenberg, Eric E Smith, Gord Gubitz, Dariush Dowlatshahi, Jayson Potts, Joel G Ray, Jon Barrett, Cheryl Bushnell, Simerpreet Bal, Wee-Shian Chan, Radha Chari, Meryem El Amrani, Shital Gandhi, Michael D Hill, Andra James, Thomas Jeerakathil, Albert Jin, Adam Kirton, Sylvain Lanthier, Andrea Lausman, Lisa Rae Leffert, Jennifer Mandzia, Bijoy Menon, Aleksandra Pikula, Alexandre Poppe, Gustavo Saposnik, Mukul Sharma, Sanjit Bhogal, Elisabeth Smitko and M Patrice Lindsay; on behalf of the Heart and Stroke Foundation Canadian Stroke Best Practice and Quality Advisory Committees; in collaboration with the Canadian Stroke Consortium in International Journal of Stroke</p