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Engineering and Evaluation of Reconstituted HDL Nanoparticles to Target Tumor-Associated Macrophages.

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dc.contributor.advisorAshish Kulkarni
dc.contributor.advisorJessica Schiffmann
dc.contributor.advisorPeter Beltramo
dc.contributor.authorMenon, Aishwarya
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentChemical Engineering
dc.date2024-03-28T19:29:08.000
dc.date.accessioned2024-04-26T18:10:26Z
dc.date.available2024-04-26T18:10:26Z
dc.date.submittedMay
dc.date.submitted2022
dc.description.abstractConventional cancer therapies such as chemotherapy and radiation often lead to severe side effects since they are unable to specifically target the tumor. Additionally, they do not guarantee the prevention of metastasis or recurrence. Recent developments on small-molecule inhibitors, such as kinase inhibitors that target cellular pathways characteristically upregulated in cancer cells, show promise. However, significant challenges such as tolerance and mutations causing drug resistance need to be overcome. Immunotherapy, wherein the host's immune system is leveraged to recognize and target cancer cells, is a better alternative that shows reduced toxicity. Macrophages are an attractive target for immunotherapy seeing as they constitute 50% of the infiltrating leukocytes in the tumor microenvironment. Their plastic nature allows them to be modulated from pro-tumor to anti-tumor phenotype. Although, it does not work for everyone, necessitating a need to monitor response to medication at earlier time points. In this thesis, I have designed an HDL mimicking nanoparticle system to target tumor associated M2 macrophages through the SRB1 receptor. The nanoparticle was optimized for better stability, better loading of the targeting peptide, and the drug as well. It was used to deliver a CSF1R inhibitor drug to successfully repolarize pro-tumor M2 macrophages to anti-tumor M1 phenotype. In addition to that, it was also used to deliver an Arginase-responsive probe that only fluoresces when engulfed by arginase-producing M2 macrophages, differentiating them from arginase non-producing M1 phenotype. Through this study, the SRB1 receptor was successfully targeted to effectively deliver small molecules. This can be used to target and modulate tumor-associated macrophages.
dc.description.degreeMaster of Science in Chemical Engineering (M.S.Ch.E.)
dc.identifier.doihttps://doi.org/10.7275/28269836
dc.identifier.orcidhttps://orcid.org/0000-0002-6446-2170
dc.identifier.urihttps://hdl.handle.net/20.500.14394/32880
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=2230&context=masters_theses_2&unstamped=1
dc.source.statuspublished
dc.subjectMacrophages
dc.subjectHDL
dc.subjectSRB1
dc.titleEngineering and Evaluation of Reconstituted HDL Nanoparticles to Target Tumor-Associated Macrophages.
dc.typeopenaccess
dc.typearticle
dc.typethesis
digcom.contributor.authorisAuthorOfPublication|email:kvavm25@gmail.com|institution:University of Massachusetts Amherst|Menon, Aishwarya
digcom.identifiermasters_theses_2/1204
digcom.identifier.contextkey28269836
digcom.identifier.submissionpathmasters_theses_2/1204
dspace.entity.typePublication
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