Theranostic photonic nanoparticles (TPNs) that cross the blood-brain barrier (BBB) and efficiently deliver a therapeutic agent to treat brain diseases, simultaneously providing optical tracking of drug delivery and release, are introduced. These TPNs are constructed by physical encapsulation of visible and/or near-infrared photonic molecules, in an ultrasmall micellar structure (<15 nm). Phytochemical curcumin is employed as a therapeutic as well as visible-emitting photonic component. In vitro BBB model studies and animal imaging, as well as ex vivo examination, reveal that these TPNs are capable of transmigration across the BBB and subsequent accumulation near the orthotopic xenograft of glioblastoma multiforme (GBM) that is the most common and aggressive brain tumor whose vasculature retains permeability-resistant properties. The intracranial delivery and release of curcumin can be visualized by imaging fluorescence produced by energy transfer from curcumin as the donor to the near-infrared emitting dye, coloaded in TPN, where curcumin induced apoptosis of glioma cells. At an extremely low dose of TPN, a significant therapeutic outcome against GBM is demonstrated noninvasively by bioluminescence monitoring of time-lapse proliferation of luciferase-expressing U-87 MG human GBM in the brain. This approach of TPN can be generally applied to a broad range of brain diseases.
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http://dx.doi.org/10.1002/adfm.201602808 | DOI Listing |
Sci Adv
January 2025
Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
Intracranial optical imaging of glioblastoma (GBM) is challenging due to the scarcity of effective probes with blood-brain barrier (BBB) permeability and sufficient imaging depth. Herein, we describe a rational strategy for designing optical probes crossing the BBB based on an electron donor-π-acceptor system to adjust the lipid/water partition coefficient and molecular weight of probes. The amphiphilic hemicyanine dye (namely, IVTPO), which exhibits remarkable optical properties and effective BBB permeability, is chosen as an efficient fluorescence/photoacoustic probe for in vivo real-time imaging of orthotopic GBM with high resolution through the intact skull.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression.
View Article and Find Full Text PDFMed Oncol
January 2025
School of Biotechnology, Centurion University of Technology and Management, Jatni, Bhubaneswar, Odisha, 752050, India.
Gliomas are aggressive intracranial tumors of the central nervous system with a poor prognosis, high risk of recurrence, and low survival rates. Radiation, surgery, and chemotherapy are traditional cancer therapies. It is very challenging to accurately image and differentiate the malignancy grade of gliomas due to their heterogeneous and infiltrating nature and the obstruction of the blood-brain barrier.
View Article and Find Full Text PDFActa Neurobiol Exp (Wars)
January 2025
Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran; Bio Environmental Health Hazards Research Center, Jiroft University of Medical Sciences, Jiroft, Iran.
In recent years, growing evidence suggests that lipopolysaccharide (LPS), a bacterial endotoxin found in the outer membrane of gram‑negative bacteria, can influence cognitive functions, particularly memory formation and retrieval. However, the underlying mechanisms through which LPS exerts its effects on memory remain incompletely understood. This review used various electronic databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published between 2000 and 2024.
View Article and Find Full Text PDFMed Chem
January 2025
Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.
Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.
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