{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10696"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10696","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Dual Receptor Uptake of Low-Density Lipoprotein Docosahexaenoic Acid (LDL-DHA) Elicits Differential Sensitivity Across Breast Cancer Subtypes","abstract":"We proposed to treat breast cancer with a novel nanomedicine previously shown to be effective in the treatment of primary liver tumors in rats. This nanoparticle is comprised of the low-density lipoprotein which acts as a carrier for the omega-3 fatty acid docosahexaenoic acid (DHA). The LDL-DHA nanoparticle has demonstrated cancer selective cytotoxicity with little ill effects on healthy cells. Our research began by selecting a panel of breast cancer cell lines representative of the various subtypes of clinical breast cancer. This panel was screened for expression of LDL and SR-B1 receptors, in addition LDL nanoparticle uptake kinetics was evaluated in each cell line. Thereafter, the cytotoxicity of LDL-DHA nanoparticles was assessed across the panel of breast cancer cells. Animal experiments showing efficacy of LDL-DHA nanoparticle are currently in progress, with the expectation that LDL-DHA treatment of tumors will induce significant tumor necrosis. Our current data suggests that our LDL-DHA nanoparticles are avidly taken up by breast cancer cells, with triple negative breast cancer cells showing some of the highest uptake, mediated by LDLR and SR-B1. LDL-DHA has a higher affinity for LDLR compared to SR-B1 with both receptors being able to mediate uptake. Concurrently, we showed that there is a reciprocal relationship between LDLR and SR-B1, where one receptor compensates for loss of the other to maintain cholesterol homeostasis. Thus, ensuring uptake of LDL-DHA nanoparticles in breast cancer cells. Moreover, LDL-DHA nanoparticles elicit significant cytotoxicity with triple negative breast cancer subtypes being most sensitive to LDL-DHA. As such, in vivo and clinical use of this nanomedicine is anticipated to be effective for metastatic breast cancer tumors with potentially more utility in triple negative breast cancer.","abstract_html":"We proposed to treat breast cancer with a novel nanomedicine previously shown to be effective in the treatment of primary liver tumors in rats. This nanoparticle is comprised of the low-density lipoprotein which acts as a carrier for the omega-3 fatty acid docosahexaenoic acid (DHA). The LDL-DHA nanoparticle has demonstrated cancer selective cytotoxicity with little ill effects on healthy cells. Our research began by selecting a panel of breast cancer cell lines representative of the various subtypes of clinical breast cancer. This panel was screened for expression of LDL and SR-B1 receptors, in addition LDL nanoparticle uptake kinetics was evaluated in each cell line. Thereafter, the cytotoxicity of LDL-DHA nanoparticles was assessed across the panel of breast cancer cells. Animal experiments showing efficacy of LDL-DHA nanoparticle are currently in progress, with the expectation that LDL-DHA treatment of tumors will induce significant tumor necrosis. Our current data suggests that our LDL-DHA nanoparticles are avidly taken up by breast cancer cells, with triple negative breast cancer cells showing some of the highest uptake, mediated by LDLR and SR-B1. LDL-DHA has a higher affinity for LDLR compared to SR-B1 with both receptors being able to mediate uptake. Concurrently, we showed that there is a reciprocal relationship between LDLR and SR-B1, where one receptor compensates for loss of the other to maintain cholesterol homeostasis. Thus, ensuring uptake of LDL-DHA nanoparticles in breast cancer cells. Moreover, LDL-DHA nanoparticles elicit significant cytotoxicity with triple negative breast cancer subtypes being most sensitive to LDL-DHA. As such, in vivo and clinical use of this nanomedicine is anticipated to be effective for metastatic breast cancer tumors with potentially more utility in triple negative breast cancer.","abstract_has_math":false,"creators":["Bower, Joseph Louis"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Malladi, Srinivas","Brekken, Rolf A.","Raj, Ganesh V.","Corbin, Ian R."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-09-08T21:50:02Z","date_published":"2025-09-08T21:50:02Z","updated_at":"2026-07-24T05:52:11Z","subjects":["Breast Neoplasms","Cell Death","Docosahexaenoic Acids","Lipoproteins, LDL","Nanoparticles","Antineoplastic Agents"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1535537207"],"render_values":[{"text":"1535537207","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10696","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Malladi, Srinivas","Brekken, Rolf A.","Raj, Ganesh V.","Corbin, Ian R."]},{"key":"dc:creator","label":"Author","values":["Bower, Joseph Louis"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-09-08T21:50:02Z","2023-08","August 2023","2025-09-08T21:50:05Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Breast Neoplasms","Cell Death","Docosahexaenoic Acids","Lipoproteins, LDL","Nanoparticles","Antineoplastic Agents"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10696","1535537207"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["We proposed to treat breast cancer with a novel nanomedicine previously shown to be effective in the treatment of primary liver tumors in rats. This nanoparticle is comprised of the low-density lipoprotein which acts as a carrier for the omega-3 fatty acid docosahexaenoic acid (DHA). The LDL-DHA nanoparticle has demonstrated cancer selective cytotoxicity with little ill effects on healthy cells. Our research began by selecting a panel of breast cancer cell lines representative of the various subtypes of clinical breast cancer. This panel was screened for expression of LDL and SR-B1 receptors, in addition LDL nanoparticle uptake kinetics was evaluated in each cell line. Thereafter, the cytotoxicity of LDL-DHA nanoparticles was assessed across the panel of breast cancer cells. Animal experiments showing efficacy of LDL-DHA nanoparticle are currently in progress, with the expectation that LDL-DHA treatment of tumors will induce significant tumor necrosis. Our current data suggests that our LDL-DHA nanoparticles are avidly taken up by breast cancer cells, with triple negative breast cancer cells showing some of the highest uptake, mediated by LDLR and SR-B1. LDL-DHA has a higher affinity for LDLR compared to SR-B1 with both receptors being able to mediate uptake. Concurrently, we showed that there is a reciprocal relationship between LDLR and SR-B1, where one receptor compensates for loss of the other to maintain cholesterol homeostasis. Thus, ensuring uptake of LDL-DHA nanoparticles in breast cancer cells. Moreover, LDL-DHA nanoparticles elicit significant cytotoxicity with triple negative breast cancer subtypes being most sensitive to LDL-DHA. As such, in vivo and clinical use of this nanomedicine is anticipated to be effective for metastatic breast cancer tumors with potentially more utility in triple negative breast cancer."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Dual Receptor Uptake of Low-Density Lipoprotein Docosahexaenoic Acid (LDL-DHA) Elicits Differential Sensitivity Across Breast Cancer Subtypes"]}]}],"canonical_facts":{"dc:contributor":["Malladi, Srinivas","Brekken, Rolf A.","Raj, Ganesh V.","Corbin, Ian R."],"dc:creator":["Bower, Joseph Louis"],"dc:date":["2025-09-08T21:50:02Z","2023-08","August 2023","2025-09-08T21:50:05Z"],"dc:description":["We proposed to treat breast cancer with a novel nanomedicine previously shown to be effective in the treatment of primary liver tumors in rats. This nanoparticle is comprised of the low-density lipoprotein which acts as a carrier for the omega-3 fatty acid docosahexaenoic acid (DHA). The LDL-DHA nanoparticle has demonstrated cancer selective cytotoxicity with little ill effects on healthy cells. Our research began by selecting a panel of breast cancer cell lines representative of the various subtypes of clinical breast cancer. This panel was screened for expression of LDL and SR-B1 receptors, in addition LDL nanoparticle uptake kinetics was evaluated in each cell line. Thereafter, the cytotoxicity of LDL-DHA nanoparticles was assessed across the panel of breast cancer cells. Animal experiments showing efficacy of LDL-DHA nanoparticle are currently in progress, with the expectation that LDL-DHA treatment of tumors will induce significant tumor necrosis. Our current data suggests that our LDL-DHA nanoparticles are avidly taken up by breast cancer cells, with triple negative breast cancer cells showing some of the highest uptake, mediated by LDLR and SR-B1. LDL-DHA has a higher affinity for LDLR compared to SR-B1 with both receptors being able to mediate uptake. Concurrently, we showed that there is a reciprocal relationship between LDLR and SR-B1, where one receptor compensates for loss of the other to maintain cholesterol homeostasis. Thus, ensuring uptake of LDL-DHA nanoparticles in breast cancer cells. Moreover, LDL-DHA nanoparticles elicit significant cytotoxicity with triple negative breast cancer subtypes being most sensitive to LDL-DHA. As such, in vivo and clinical use of this nanomedicine is anticipated to be effective for metastatic breast cancer tumors with potentially more utility in triple negative breast cancer."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10696","1535537207"],"dc:language":["en"],"dc:subject":["Breast Neoplasms","Cell Death","Docosahexaenoic Acids","Lipoproteins, LDL","Nanoparticles","Antineoplastic Agents"],"dc:title":["Dual Receptor Uptake of Low-Density Lipoprotein Docosahexaenoic Acid (LDL-DHA) Elicits Differential Sensitivity Across Breast Cancer Subtypes"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:11Z"}