Most potent therapeutics are unable to cross the blood-brain barrier following systemic administration, which necessitates the development of unconventional, clinically applicable drug delivery systems. With the given challenges, biologically active vehicles are crucial to accomplishing this task. We now report a new method for drug delivery that utilizes living cells as vehicles for drug carriage across the blood brain barrier. Cellular backpacks, 7-10 μm diameter polymer patches of a few hundred nanometers in thickness, are a potentially interesting approach, because they can act as drug depots that travel with the cell-carrier, without being phagocytized. Backpacks loaded with a potent antioxidant, catalase, were attached to autologous macrophages and systemically administered into mice with brain inflammation. Using inflammatory response cells enabled targeted drug transport to the inflamed brain. Furthermore, catalase-loaded backpacks demonstrated potent therapeutic effects deactivating free radicals released by activated microglia in vitro. This approach for drug carriage and release can accelerate the development of new drug formulations for all the neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.biomaterials.2017.06.017 | DOI Listing |
Neuro Oncol
January 2025
Department of Medicine, Division of Experimental Medicine, McGill University.
Background: Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Roswell Park Cancer Institute, Buffalo, NY, United States.
Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC.
Patients And Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment).
Sci Transl Med
January 2025
University of Strasbourg, INSERM, Strasbourg Translational Neuroscience & Psychiatry STEP-CRBS, UMR-S 1329, 67000 Strasbourg, France.
Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic and mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep.
View Article and Find Full Text PDFACS Nano
January 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Contemporary osteoporosis treatment often neglects the intricate interactions among immune cells, signaling proteins, and cytokines within the osteoporotic microenvironment. Here, we developed core-shell nanocapsules composed of a cationized lactoferrin core and an alendronate polymer shell. By tuning the size of these nanocapsules and leveraging the alendronate shell, we enabled precise delivery of small interfering RNA targeting the Semaphorin 4D gene (siSema4D) to specific bone sites.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
January 2025
Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Purpose: The positron range effect can impair PET image quality of Gallium-68 (Ga). A positron range correction (PRC) can be applied to reduce this effect. In this study, the effect of a tissue-independent PRC for Ga was investigated on patient data.
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