Human neural stem cells (hNSCs) have the potential to differentiate into various neural cell types, including cortical neurons, which are of particular interest for understanding and treating neurodegenerative diseases. However, traditional 2D culture methods are limited in their ability to accurately mimic the physiologically relevant microenvironment, leading to slow differentiation rates and low yields of mature neurons. In this study, we developed and optimized 3D chitosan scaffolds to promote the more efficient differentiation of hNSCs into cortical neurons.
View Article and Find Full Text PDFCancer remains one of the leading causes of death, with breast, liver, and pancreatic cancers significantly contributing to this burden. Traditional treatments face issues including dose-limiting toxicity, drug resistance, and limited efficacy. Combining therapeutic agents can enhance effectiveness and reduce toxicity, but separate administration often leads to inefficiencies due to differing pharmacokinetics and biodistribution.
View Article and Find Full Text PDFStem cell-based therapy holds promise for cartilage regeneration in treating knee osteoarthritis (KOA). Injectable hydrogels have been developed to mimic the extracellular matrix (ECM) and facilitate stem cell growth, proliferation, and differentiation. However, these hydrogels face limitations such as poor mechanical strength, inadequate biocompatibility, and suboptimal biodegradability, collectively hindering their effectiveness in cartilage regeneration.
View Article and Find Full Text PDFThe maintenance and expansion of human neural stem cells (hNSCs) in 3D tissue scaffolds is a promising strategy in producing cost-effective hNSCs with quality and quantity applicable for clinical applications. A few biopolymers have been extensively used to fabricate 3D scaffolds, including hyaluronic acid, collagen, alginate, and chitosan, due to their bioactive nature and availability. However, these polymers are usually applied in combination with other biomolecules, leading to their responses difficult to ascribe to.
View Article and Find Full Text PDFACS Appl Mater Interfaces
June 2024
Intervertebral disc degeneration (IDD) is a progressive condition and stands as one of the primary causes of low back pain. Cell therapy that uses nucleus pulposus (NP)-like cells derived from human induced pluripotent stem cells (hiPSCs) holds great promise as a treatment for IDD. However, the conventional two-dimensional (2D) monolayer cultures oversimplify cell-cell interactions, leading to suboptimal differentiation efficiency and potential loss of phenotype.
View Article and Find Full Text PDFSingle-atom nanozymes with well-defined atomic structures and electronic coordination environments can effectively mimic the functions of natural enzymes. However, the costly and intricate preparation processes have hindered further exploration and application of these single-atom nanozymes. In this study, we presented a synthesis technique for creating Fe-N central single-atom doped graphene quantum dot (FeN/GQDs) nanozymes using a one-step solvothermal process, where individual iron atoms form strong bonds with graphene quantum dots through nitrogen coordination.
View Article and Find Full Text PDFMagnetite-based nanozymes have attracted great interest for catalytic cancer therapy enabled by catalyzing hydrogen peroxide (H O ) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, their therapeutic efficacies remain low due to insufficient •OH. Here, a light-responsive carbon-encapsulated magnetite nanodoughnuts (CEMNDs) with dual-catalytic activities for photothermal-enhanced chemodynamic therapy (CDT) is reported.
View Article and Find Full Text PDFHuman neural stem cells (hNSCs) possess remarkable potential for regenerative medicine in the treatment of presently incurable diseases. However, a key challenge lies in producing sufficient quantities of hNSCs, which is necessary for effective treatment. Dynamic culture systems are recognized as a powerful approach to producing large quantities of hNSCs required, where microcarriers play a critical role in supporting cell expansion.
View Article and Find Full Text PDFmRNA-based therapeutics have emerged as a promising strategy for cancer treatment. However, the effective delivery of mRNA into hard-to-transfect cancer cells remains a significant challenge. This study introduces a novel approach that utilizes iron oxide nanoparticles (NPs) synthesized through a layer-by-layer (LbL) method for safe and efficient mRNA delivery.
View Article and Find Full Text PDFNatural polymer-based porous scaffolds have been investigated to serve as three-dimensional (3D) tumor models for drug screening owing to their structural properties with better resemblance to human tumor microenvironments than two-dimensional (2D) cell cultures. In this study, a 3D chitosan-hyaluronic acid (CHA) composite porous scaffold with tunable pore size (60, 120 and 180 µm) was produced by freeze-drying and fabricated into a 96-array platform for high-throughput screening (HTS) of cancer therapeutics. We adopted a self-designed rapid dispensing system to handle the highly viscous CHA polymer mixture and achieved a fast and cost-effective large-batch production of the 3D HTS platform.
View Article and Find Full Text PDFTheranostic nanoparticles' potential in tumor treatment has been widely acknowledged thanks to their capability of integrating multifaceted functionalities into a single nanosystem. Theranostic nanoparticles are typically equipped with an inorganic core with exploitable physical properties for imaging and therapeutic functions, bioinert coatings for improved biocompatibility and immunological stealth, controlled drug-loading-release modules, and the ability to recognize specific cell type for uptake. Integrating multiple functionalities in a single nanosized construct require sophisticated molecular design and precise execution of assembly procedures.
View Article and Find Full Text PDFHuman-induced pluripotent stem cells (hiPSCs) cultured in 3D matrices hold great promise in disease modeling, drug discovery, and tissue regeneration. Uniform cell distribution in a 3D structure is critical to the growth and function of hiPSCs, yet cell seeding in 3D matrices often remains superficial, leading to limited cell proliferation and compromised pluripotency. Here, an approach to improve cell penetration depth of hiPSCs in 3D scaffolds modified with hiPSCs conditioned medium (CM) is reported.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2023
Glioma is a deadly form of brain cancer, and the difficulty of treating glioma is exacerbated by the chemotherapeutic resistance developed in the tumor cells over the time of treatment. siRNA can be used to silence the gene responsible for the increased resistance, and sensitize the glioma cells to drugs. Here, iron oxide nanoparticles functionalized with peptides (NP-CTX-R) were used to deliver siRNA to silence O6-methylguanine-DNA methyltransferase (MGMT) to sensitize tumor cells to alkylating drug, Temozolomide (TMZ).
View Article and Find Full Text PDFMicromachines (Basel)
October 2022
Cells cultured in three-dimensional scaffolds express a phenotype closer to in vivo cells than cells cultured in two-dimensional containers. Natural polymers are suitable materials to make three-dimensional scaffolds to develop disease models for high-throughput drug screening owing to their excellent biocompatibility. However, natural polymer solutions have a range of viscosities, and none of the currently available liquid dispensers are capable of dispensing highly viscous polymer solutions.
View Article and Find Full Text PDFStem cell therapy and research for neural diseases depends on reliable reproduction of neural stem cells. Chitosan-based materials have been proposed as a substrate for culturing human neural stem cells (hNSCs) in the pursuit of clinically compatible culture conditions that are chemically defined and compliant with good manufacturing practices. The physical and biochemical properties of chitosan and chitin are strongly regulated by the degree of deacetylation (DD).
View Article and Find Full Text PDFThe liver is a vital organ that functions to detoxify the body. Liver cancer and infectious diseases such as influenza and malaria can fatally compromise liver function. mRNA delivery is a relatively new means of therapeutic treatment which enables expression of tumor or pathogenic antigens, and elicits immune responses for therapeutic or prophylactic effect.
View Article and Find Full Text PDFAs one of the leading causes of global mortality, cancer has prompted extensive research and development to advance efficacious drug discovery, sustained drug delivery and improved sensitivity in diagnosis. Towards these applications, nanofibers synthesized by electrospinning have exhibited great clinical potential as a biomimetic tumor microenvironment model for drug screening, a controllable platform for localized, prolonged drug release for cancer therapy, and a highly sensitive cancer diagnostic tool for capture and isolation of circulating tumor cells in the bloodstream and for detection of cancer-associated biomarkers. This review provides an overview of applied nanofiber design with focus on versatile electrospinning fabrication techniques.
View Article and Find Full Text PDFMicromachines (Basel)
July 2022
The assessment of the biodegradability of nanomaterials is of pragmatic importance for understanding the interactions between nanomaterials and biological systems and for the determination of ultimate fate of these materials as well as their potential use. We recently developed carbon-based biconcave nanodisks (CBBNs) serving as a versatile nanocarrier for enhanced accumulation in tumors and combined photothermal-chemotherapy. Here, we investigate both the enzymatic and cellular degradation of CBBNs by monitoring their cellular response with electron microscopy, near-infrared absorbance spectroscopy, and cell viability and oxidative stress assessments.
View Article and Find Full Text PDFBreast cancer has attracted tremendous research interest in treatment development as one of the major threats to public health. The use of non-viral carriers for therapeutic DNA delivery has shown promise in treating various cancer types, including breast cancer, due to their high DNA loading capacity, high cell transfection efficiency, and design versatility. However, cytotoxicity and large sizes of non-viral DNA carriers often raise safety concerns and hinder their applications in the clinic.
View Article and Find Full Text PDFMater Today (Kidlington)
November 2021
Triple negative breast cancer is difficult to treat effectively, due to its aggressiveness, drug resistance, and lack of the receptors required for hormonal therapy, particularly at the metastatic stage. Here, we report the development and evaluation of a multifunctional nanoparticle formulation containing an iron oxide core that can deliver doxorubicin, a cytotoxic agent, and polyinosinic:polycytidylic acid (Poly IC), a TLR3 agonist, in a targeted and simultaneous fashion to both breast cancer and dendritic cells. Endoglin-binding peptide (EBP) is used to target both TNBC cells and vasculature epithelia.
View Article and Find Full Text PDFOsteoarthritis (OA) is a serious chronic and degenerative disease that increasingly occurs in the aged population. Its current clinical treatments are limited to symptom relief and cannot regenerate cartilage. Although a better understanding of OA pathophysiology has been facilitating the development of novel therapeutic regimen, delivery of therapeutics to target sites with minimal invasiveness, high retention, and minimal side effects remains a challenge.
View Article and Find Full Text PDFCancer is a genetic disease originating from the accumulation of gene mutations in a cellular subpopulation. Although many therapeutic approaches have been developed to treat cancer, recent studies have revealed an irrefutable challenge that tumors evolve defenses against some therapies. Gene therapy may prove to be the ultimate panacea for cancer by correcting the fundamental genetic errors in tumors.
View Article and Find Full Text PDFFront Bioeng Biotechnol
July 2021
Fluorescence microscopy is commonly used to image specific parts of a biological system, and is applicable for early diagnosis of cancer. Current fluorescent probes, such as organic dyes and quantum dots, suffer from poor solubility and high toxicity, respectively, demonstrating a need for a colloidal stable and non-toxic fluorescent probe. Here we present an iron oxide and carbon dot (CD) based nanoparticle (CNPCP) that displays optical properties similar to those of conventional fluorescent probe and also exhibits good biocompatibility.
View Article and Find Full Text PDFNanoscale Horiz
September 2021
Cancer immunotherapy is a novel approach to cancer treatment that leverages components of the immune system as opposed to chemotherapeutics or radiation. Cell migration is an integral process in a therapeutic immune response, and the ability to track and image the migration of immune cells in vivo allows for better characterization of the disease and monitoring of the therapeutic outcomes. Iron oxide nanoparticles (IONPs) are promising candidates for use in immunotherapy as they are biocompatible, have flexible surface chemistry, and display magnetic properties that may be used in contrast-enhanced magnetic resonance imaging (MRI).
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