Chemistry & Biochemistry Seminar Abstract

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Abstract Location and Details

When: Thursday, February 8, 2018
Where: Room 114 Smith Hall, 11:00 a.m.

Brandon Pratt, senior Biochemistry major

The Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction-Mediated Drug Delivery to Specific Cell Populations

Designing chemotherapeutic drugs which can be targeted to specific recipient cell populations is currently challenging due to limitations in drug delivery systems. Recently, as a means of overcoming drug delivery limitations, lipid membrane vesicles called Connectosomes have been engineered that harness the endogenous capability of cells to pass cellular contents through gap junction channels. In a previously published study, these Connectosomes were proven capable of effectively delivering molecular cargo. However, because the proteins required to create gap junctions are found ubiquitously throughout mammalian tissues, non-specific interactions between Connectosomes and healthy cells could potentially limit their translational relevance in treating disease. The aim of the study at hand is to create targeting ligands on the surfaces of Connectosomes (creating targeted Connectosomes) that selectively enhance interactions between Connectosomes and cells expressing a model-receptor. Through a series of experiments utilizing flow cytometry and fluorescent and bright field microscopy, targeted Connectosomes were found to have up to a 25-fold increase in binding to target cells in comparison to off-target cells. Furthermore, it was shown that targeted Connectosomes lowered the effective dose of the chemotherapeutic drug doxorubicin needed to kill cells by an order of magnitude when compared to traditional drug delivery systems, indicating a substantial increase in therapeutic efficacy. Combined, these results provide a critical step in fully realizing the therapeutic potential of utilizing the cell’s own machinery via gap junctions for delivering chemotherapeutics to a wide range of cell types.

Emily Brookmire, Biochemistry major

Pulmonary Administration of Functionalized Nanoparticles Significantly Reduces Beta-Amyloid in the Brain of an Alzheimer’s Disease Murine Model (Nano Research 2016, vol. 9, issue 7)

Alzheimer’s disease (AD) is one of the United States’ leading causes of death for people over 65 years old, and because of its high rate of fatality, debilitating symptoms, and healthcare costs, it has become a topic of interest in the biomedical and biochemical research arena. AD is characterized by the accumulation of plaques in the cerebrum created by the β-amyloid (1-42) protein, effectively causing loss of nervous system function. Treatment of the disease has been historically difficult, as most pharmaceutical treatments are unable to cross the blood brain barrier to access the β-amyloid plaques in the brain. The current study presents a bifunctional liposome nanoparticle with an encapsulated modified apolipoprotein as treatment for AD by denaturation of the β-amyloid (1-42) protein and its associated plaques, demonstrated in a murine model. The liposome nanoparticles were radiolabeled and given as treatment to mice via intratracheal route. Homogenized brain hemispheres of sacrificed mice were analyzed with ELISA to detect the radiolabeled β-amyloid (1-42) in treated and control mice. Findings show a 44% reduction of β-amyloid (1-42) plaques in treated mice up to 72 hours after first administration of treatment. Further studies using this nanoparticle and modified apolipoprotein could point to an approved treatment of AD due to its promising outlook in this study.

Last Updated 2/1/18

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