Water-soluble endohedral metallofullerenes: new horizons for biomedical applications.

Endohedral metallofullerenes (EMFs) offer a safe avenue to manipulate metals important to biomedical applications such as MRI contrast, X-ray contrast, radiolabeling, radiotherapy, chemotherapy, and the control of inflammation by scavenging reactive oxygen species (ROS). Moreover, functionalizing the double bonds on the surface of EMFs modifies their solubility, supramolecular behaviour, binding, targeting characteristics, and physical properties. While most existing water-soluble derivatives possess a statistical mixture of appended functional groups, progress has been made in creating molecularly-precise derivatives with a defined number of surface functional groups, leading to potentially more nuanced control of their behaviour and properties.

Aptameric Fluorescent Biosensors for Liver Cancer Diagnosis.

Liver cancer is a prevalent global health concern with a poor 5-year survival rate upon diagnosis. Current diagnostic techniques using the combination of ultrasound, CT scans, MRI, and biopsy have the limitation of detecting detectable liver cancer when the tumor has already progressed to a certain size, often leading to late-stage diagnoses and grim clinical treatment outcomes. To this end, there has been tremendous interest in developing highly sensitive and selective biosensors to analyze related cancer biomarkers in the early stage diagnosis and prescribe appropriate treatment options.

Advanced Drug Delivery Modulation via Hybrid Nanofibers Enhances Stem Cell Differentiation.

Seamlessly integrating soluble factors onto biomedical scaffolds with a precisely manufactured topography for efficient cell control remains elusive since many scaffold fabrication techniques degrade payloads. Surface adsorption of payloads onto synthesized nanoscaffolds retains bioactivity by removing exposure to harsh processing conditions at the expense of inefficient drug loading and uncontrolled release. Herein, we present a nanomaterial composite scaffold paradigm to improve physicochemical surface adsorption pharmacokinetics.

Hybrid Graphene-Gold Nanoparticle-based Nucleic Acid Conjugates for Cancer-Specific Multimodal Imaging and Combined Therapeutics.

Nanoparticle-based nucleic acid conjugates (NP-NACs) hold great promise for theragnostic (diagnostic and therapeutic) applications. However, several limitations have hindered the realization of their full potential in the clinical treatment of cancer and other diseases. In diagnosis, NP-NACs, combined with conventional optical sensing systems, have been applied for cancer detection , but low signal-to-noise ratios limit their broad applications.

4D-Printed Transformable Tube Array for High-Throughput 3D Cell Culture and Histology.

3D cell cultures are rapidly emerging as a promising tool to model various human physiologies and pathologies by closely recapitulating key characteristics and functions of in vivo microenvironment. While high-throughput 3D culture is readily available using multi-well plates, assessing the internal microstructure of 3D cell cultures still remains extremely slow because of the manual, laborious, and time-consuming histological procedures. Here, a 4D-printed transformable tube array (TTA) using a shape-memory polymer that enables massively parallel histological analysis of 3D cultures is presented.

Functional nanoarrays for investigating stem cell fate and function.

Stem cells show excellent potential in the field of tissue engineering and regenerative medicine based on their excellent capability to not only self-renew but also differentiate into a specialized cell type of interest. However, the lack of a non-destructive monitoring system makes it challenging to identify and characterize differentiated cells before their transplantation without compromising cell viability. Thus, the development of a non-destructive monitoring method for analyzing cell function is highly desired and can significantly benefit stem cell-based therapies.

Developments in Bio-Inspired Nanomaterials for Therapeutic Delivery to Treat Hearing Loss.

Sensorineural hearing loss affects millions of people worldwide and is a growing concern in the aging population. Treatment using aminoglycoside antibiotics for infection and exposure to loud sounds contribute to the degeneration of cochlear hair cells and spiral ganglion neurons. Cell loss impacts cochlear function and causes hearing loss in ∼ 15% of adult Americans (∼36 million).

Programmed degradation of a hierarchical nanoparticle with redox and light responsivity for self-activated photo-chemical enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) has recently emerged as a promising treatment for cancer due to the high specificity of CDT towards tumor microenvironment (TME). However, the low efficiency of reactive oxygen species (ROS) generation and the robust ROS defensive mechanisms in cancer cells remain critical hurdles for current CDT. Addressing both challenges in a single platform, we developed a novel redox and light-responsive (RLR) nanoparticle with a core-shell structure.

Nondestructive Characterization of Stem Cell Neurogenesis by a Magneto-Plasmonic Nanomaterial-Based Exosomal miRNA Detection.

The full realization of stem cell-based treatments for neurodegenerative diseases requires precise control and characterization of stem cell fate. Herein, we report a multifunctional magneto-plasmonic nanorod (NR)-based detection platform to address the limitations associated with the current destructive characterization methods of stem cell neurogenesis. Exosomes and their inner contents have been discovered to play critical roles in cell-cell interactions and intrinsic cellular regulations and have received wide attention as next-generation biomarkers.

Tumor Homing Reactive Oxygen Species Nanoparticle for Enhanced Cancer Therapy.

Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their tumor-targeting ability and high drug-loading capacity. However, the nonspecific release of toxic DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the tumors. Herein, we report a tumor homing reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant tumors.

A biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy.

Stem cell transplantation, as a promising treatment for central nervous system (CNS) diseases, has been hampered by crucial issues such as a low cell survival rate, incomplete differentiation, and limited neurite outgrowth in vivo. Addressing these hurdles, scientists have designed bioscaffolds that mimic the natural tissue microenvironment to deliver physical and soluble cues. However, several significant obstacles including burst release of drugs, insufficient cellular adhesion support, and slow scaffold degradation rate remain to be overcome before the full potential of bioscaffold-based stem-cell therapies can be realized.

Nondestructive Real-Time Monitoring of Enhanced Stem Cell Differentiation Using a Graphene-Au Hybrid Nanoelectrode Array.

Stem cells have attracted increasing research interest in the field of regenerative medicine because of their unique ability to differentiate into multiple cell lineages. However, controlling stem cell differentiation efficiently and improving the current destructive characterization methods for monitoring stem cell differentiation are the critical issues. To this end, multifunctional graphene-gold (Au) hybrid nanoelectrode arrays (NEAs) to: (i) investigate the effects of combinatorial physicochemical cues on stem cell differentiation, (ii) enhance stem cell differentiation efficiency through biophysical cues, and (iii) characterize stem cell differentiation in a nondestructive real-time manner are developed.

Advanced Gene Manipulation Methods for Stem Cell Theranostics.

In the field of tissue engineering, autologous cell sources are ideal to prevent adverse immune responses; however, stable and reliable cell sources are limited. To acquire more reliable cell sources, the harvesting and differentiation of stem cells from patients is becoming more and more common. To this end, the need to control the fate of these stem cells before transplantation for therapeutic purposes is urgent.

Multidimensional nanomaterials for the control of stem cell fate.

Current stem cell therapy suffers low efficiency in giving rise to differentiated cell lineages, which can replace the original damaged cells. Nanomaterials, on the other hand, provide unique physical size, surface chemistry, conductivity, and topographical microenvironment to regulate stem cell differentiation through multidimensional approaches to facilitate gene delivery, cell-cell, and cell-ECM interactions. In this review, nanomaterials are demonstrated to work both alone and synergistically to guide selective stem cell differentiation.

Large-Scale Nanoelectrode Arrays to Monitor the Dopaminergic Differentiation of Human Neural Stem Cells.

A novel cell-based biosensing platform is developed using a combination of sequential laser interference lithography and electrochemical deposition methods. This enables the sensitive discrimination of dopaminergic cells from other types of neural cells in a completely nondestructive manner. This platform and detection strategy may become an effective noninvasive in situ monitoring tool that can be used to determine stem cell fate for various regenerative applications.

Induction of stem-cell-derived functional neurons by NanoScript-based gene repression.

Even though gene repression is a powerful approach to exogenously regulate cellular behavior, developing a platform to effectively repress targeted genes, especially for stem-cell applications, remains elusive. Herein, we introduce a nanomaterial-based platform that is capable of mimicking the function of transcription repressor proteins to downregulate gene expression at the transcriptional level for enhancing stem-cell differentiation. We developed the "NanoScript" platform by integrating multiple gene repression molecules with a nanoparticle.

Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures.

Human neural stem cells (hNSCs) cultured on graphene-nanoparticle hybrid structures show a unique behavior wherein the axons from the differentiating hNSCs show enhanced growth and alignment. We show that the axonal alignment is primarily due to the presence of graphene and the underlying nanoparticle monolayer causes enhanced neuronal differentiation of the hNSCs, thus having great implications of these hybrid-nanostructures for neuro-regenerative medicine.