A5010824862- Nanoparticle-Based Drug Delivery
- Characterization and Applications of Magnetic Nanoparticles
- Nanoplatforms for cancer theranostics
- Magnetic and Electromagnetic Effects
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Microfluidic and Bio-sensing Technologies
- Glioma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Hedgehog Signaling Pathway Studies
- Anesthesia and Pain Management
- Advanced Polymer Synthesis and Characterization
- Lanthanide and Transition Metal Complexes
- biodegradable polymer synthesis and properties
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Cancer Treatment and Pharmacology
- TGF-β signaling in diseases
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Analytical Chemistry and Chromatography
- Electrospun Nanofibers in Biomedical Applications
- Graphene and Nanomaterials Applications
- Nanocluster Synthesis and Applications
- Pain Mechanisms and Treatments
University of North Carolina at Chapel Hill
2016-2025
Carolina Institute for NanoMedicine
2025
University of North Carolina Health Care
2022
NewPath Research
2018
North Carolina State University
2018
Institute of Nanotechnology
2016
CeNTech
2016
Hebrew University of Jerusalem
2006-2014
University of Nebraska Medical Center
2011-2012
Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes cancer treatments, but face challenges because differential solubility and fairly low threshold incorporation many drugs. Here we demonstrate that this approach be used to greatly the treatment etoposide (ETO) platinum drug combination ("EP/PE") therapy is backbone prevalent deadly small cell lung (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx)...
Targeting oncogenic pathways holds promise for brain tumor treatment, but inhibition of Sonic Hedgehog (SHH) signaling has failed in SHH-driven medulloblastoma. Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability treatment-resistant populations. Using single-cell RNA-seq tracing, we analyzed cellular medulloblastomas transgenic, medulloblastoma-prone mice, responses to SHH-pathway inhibitor vismodegib. In untreated...
Abstract Significant advances in physicochemical properties of polymeric micelles enable optimization therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect micelle morphology on pharmacological efficacy is not adequately addressed. This work addresses this gap by assessing with spherical worm‐like morphologies. It observed that poly(2‐oxazoline)‐based can be elongated over time from a structure to structure, elongation influenced several...
OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies target this cell population. Here, we investigate the therapeutic potential of brain-penetrant orally bioavailable, OLIG2 inhibitor CT-179, using SHH-MB explant organoids, PDX GEM models. We find that CT-179 disrupts dimerization, phosphorylation DNA binding alters cell-cycle kinetics, increasing differentiation apoptosis....
Abstract Motion of micron and sub-micron size magnetic particles in alternating fields can activate mechanosensitive cellular functions or physically destruct cancer cells. However, such effects are usually observed with relatively large (>250 nm) that would be difficult if at all possible to deliver remote sites the body treat disease. Here we show a completely new mechanism selective toxicity superparamagnetic nanoparticles (SMNP) 7 8 nm diameter These coated by block copolymers, which...
Many current nanoformulations of taxanes are hampered by low drug‐loading capacity and unfavorable physicochemical characteristics such as large particles size (>100 nm) and/or uniformity. We have previously reported on taxane nanoformulations, based poly(2‐oxazoline) polymeric micelles that display an extremely high loading (>40% w/w) particle below 50 nm. Previous work was a triblock copolymer having poly(2‐butyl‐2‐oxazoline) the hydrophobic block poly(2‐methyl‐2‐oxazoline)...
Polymeric micelle formulation of an immune modulator improves survival in a highly aggressive model non–small cell lung cancer.
The therapeutic potential of CDK4/6 inhibitors for brain tumors has been limited by recurrence. To address recurrence, we tested a nanoparticle formulation inhibitor palbociclib (POx-Palbo) in mice genetically-engineered to develop SHH-driven medulloblastoma, alone or combination with specific agents suggested our analysis. Nanoparticle encapsulation reduced toxicity, enabled parenteral administration, improved CNS pharmacokinetics, and extended mouse survival, but recurrence persisted....
The biocompatibility of oxidized dextran (40 kDa) was investigated in vitro. contribution aldehyde groups to the toxicity polymer-drug conjugates, such as dextran-amphotericin B (AmB) evaluated. Oxidized proved be toxic against RAW 264.7 cell line with an IC50 3 micromol/mL aldehydes. Modification and their reaction ethanolamine reduced at least 15-fold. Accordingly, antifungal antileishmanial dextran-AmB imine conjugate, which contains unreacted groups, modified compared amine conjugates....
Magnetic nanoparticles (MNPs) accumulate at disease sites with the aid of magnetic fields; biodegradable MNPs can be designed to facilitate drug delivery, influence diagnostics, tissue regeneration and permit protein purification. Because their limited toxicity, are widely used in theranostics, simultaneously facilitating diagnostics therapeutics. To realize therapeutic end points, iron oxide nanoparticle cores (5–30 nm) encapsulated a biocompatible polymer shell cargos. Although limited,...
Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis hypoplasia mice. Co-deletions of either or Bax Bak prevented Atr-deleted CGNPs, but failed to fully...
Computer-assisted strategy for drug delivery leads to discovery of polymeric micelle formulations poorly soluble drugs.
We report a nanoparticle formulation of the SHH-pathway inhibitor vismodegib that improves efficacy for medulloblastoma, while reducing toxicity. Limited blood–brain barrier (BBB) penetration and dose-limiting extitle/citraneural toxicities complicate systemic therapies brain tumors. Vismodegib is FDA-approved SHH-driven basal cell carcinoma, but implementation medulloblastoma has been limited by inadequate excessive bone To address these issues through optimized drug delivery, we formulated...