Browsing by Author "Scully, Mackenzie A."
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Item Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple-Negative Breast Cancer(Advanced Therapeutics, 2024-04-26) Dang, Megan N.; Suri, Sejal; Li, Kejian; Gomez Casas, Carolina; Stigliano, Gianna; Riley, Rachel S.; Scully, Mackenzie A.; Hoover, Elise C.; Aboeleneen, Sara B.; Kramarenko, George C.; Day, Emily S.The paucity of targeted therapies for triple-negative breast cancer (TNBC) causes patients with this aggressive disease to suffer a poor clinical prognosis. A promising target for therapeutic intervention is the Wnt signaling pathway, which is activated in TNBC cells when extracellular Wnt ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors. This stabilizes intracellular β-catenin proteins that in turn promote transcription of oncogenes that drive tumor growth and metastasis. To suppress Wnt signaling in TNBC cells, this work develops therapeutic nanoparticles (NPs) functionalized with FZD7 antibodies and β-catenin small interfering RNAs (siRNAs). The antibodies enable TNBC cell specific binding and inhibit Wnt signaling by locking FZD7 receptors in a ligand unresponsive state, while the siRNAs suppress β-catenin through RNA interference. Compared to NPs coated with antibodies or siRNAs individually, NPs coated with both agents more potently reduce the expression of several Wnt related genes in TNBC cells, leading to greater inhibition of cell proliferation, migration, and spheroid formation. In two murine models of metastatic TNBC, the dual antibody/siRNA nanocarriers outperformed controls in terms of inhibiting tumor growth, metastasis, and recurrence. These findings demonstrate suppressing Wnt signaling at both the receptor and mRNA levels via antibody/siRNA nanocarriers is a promising approach to combat TNBC.Item Combination cancer imaging and phototherapy mediated by membrane-wrapped nanoparticles(International Journal of Hyperthermia, 2023-10-30) Aboeleneena, Sara B.; Scully, Mackenzie A.; Kramarenko, George C.; Day, Emily S.Cancer is a devastating health problem with inadequate treatment options. Many conventional treatments for solid-tumor cancers lack tumor specificity, which results in low efficacy and off-target damage to healthy tissues. Nanoparticle (NP)-mediated photothermal therapy (PTT) is a promising minimally invasive treatment for solid-tumor cancers that has entered clinical trials. Traditionally, NPs used for PTT are coated with passivating agents and/or targeting ligands, but alternative coatings are being explored to enhance tumor specific delivery. In particular, cell-derived membranes have emerged as promising coatings that improve the biointerfacing of photoactive NPs, which reduces their immune recognition, prolongs their systemic circulation and increases their tumor accumulation, allowing for more effective PTT. To maximize treatment success, membrane-wrapped nanoparticles (MWNPs) that enable dual tumor imaging and PTT are being explored. These multifunctional theranostic NPs can be used to enhance tumor detection and/or ensure a sufficient quantity of NPs that have arrived in the tumor prior to laser irradiation. This review summarizes the current state-of-the-art in engineering MWNPs for combination cancer imaging and PTT and discusses considerations for the path toward clinical translation.Item Membrane-wrapped nanoparticles for nucleic acid delivery(Biomaterials Science, 2022-06-29) Scully, Mackenzie A.; Sterin, Eric H.; Day, Emily S.There is an unmet need for carriers that can deliver nucleic acids (NAs) to cancer cells and tumors to perpetuate gene regulation and manage disease progression. Membrane-wrapped nanoparticles (NPs) can be loaded with exogenously designed nucleic acid cargoes, such as plasmid deoxyribonucleic acid (pDNA), messenger ribonucleic acid (mRNA), small interfering RNA (siRNA), microRNA (miRNA), and immunostimulatory CpG oligodeoxynucleotides (CpG ODNs), to mitigate challenges presented by NAs’ undesirable negative charge, hydrophilicity, and relatively large size. By conjugating or encapsulating NAs within membrane-wrapped NPs, various physiological barriers can be overcome so that NAs experience increased blood circulation half-lives and enhanced accumulation in intended sites. This review discusses the status of membrane-wrapped NPs as NA delivery vehicles and their advancement in gene regulation for cancer management in vitro and in vivo. With continued development, membrane-wrapped NPs have great potential as future clinical tools to treat cancer and other diseases with a known genetic basis.