Platelet-like proteoliposomes enable active drug delivery to infarcted heart tissue

Event Abstract Back to Event Platelet-like proteoliposomes enable active drug delivery to infarcted heart tissue Bill Cheng1*, Elsie Toh1*, Egretta Chen1*, Yuan-Chih Chang2*, Lee-Young Chau1*, Peilin Chen3* and Patrick Hsieh1* 1 Academia Sinica, Institute of Biomedical Science, Taiwan 2 Academia Sinica, Institute of Cellular and Organismic Biology, Taiwan 3 Academia Sinica, Research Center for Applied Sciences, Taiwan Introduction: To date, ischemic heart disease (IHD) continues to be the major cause of death in many countries. It is well established that the recruitment of monocytes to the infarcted area is a significant contributor to pathophysiology of the disease. Once these circulating monocytes cross the endothelium they becomes macrophages, which then causes more damages to the infarct heart through their profound inflammatory activity. Unfortunately, drugs that target these macrophages or other drug targets, often have undesired off-targeting effects as most of them rely on the enhanced permeability retention (EPR) effect in getting to the target area. Since platelets are known to bind to the circulating monocytes in patients with IHD, it is hypothesized that active drug targeting to infarcted heart can be achieved through the interaction of platelet-like proteoliposomes (PLPs) with the circulating monocytes. In this study, cobalt protoporphyrin (CoPP), a small molecule that inhibits cardiac macrophages’ inflammatory activity while inducing toxicity at other organs was used as the drug example. Materials and Methods: The fabrication of PLPs involved mixing platelet membrane proteins with DiI-labelled DOPC/cholesterol. Bioactivity of PLPs was characterized by in vitro immunofluorescence assay. Biodistribution of control liposomes and PLPs in murine model of I/R (ischemia-reperfusion) injury was analyzed by high performance liquid chromatography (HPLC). Histological stainings were performed to analyze the size of infarct area in the murine model after i.v. injected with PLPs-encapsulated CoPP. Likewise, echocardiography and blood tests were used to access cardiac functions of murine model of myocardial infarction (MI) after i.v. injection of PLPs-encapsulated CoPP. Results and Discussion: Fluorescence images revealed that control liposomes were phagocytized by murine endothelial cells, monocytes and macrophages. In contrast, PLPs only showed positive interactions with monocytes and macrophages, suggesting that PLPs would not induce undesired thrombosis through the interactions with endothelium. Compared to control liposomes, biodistribution study revealed significant amount of PLPs were detected in the heart tissue of the murine model of I/R injury when injected after ~72 hours of reperfusion, which is the time that the amount of the recruited monocytes peaks at. Moreover, the mice treated with PLPs-encapsulated CoPP showed significant reduction in the infarct area compared to liposome-encapsulated CoPP. Improvement in cardiac functions in murine model of MI was also seen when treated with PLPs-encapsulated CoPP. Unlike free CoPP or liposome-encapsulated CoPP, the mice treated with PLPs-encapsulated CoPP showed significant improvement in cardiac functions, while minimizing the known side-effects of CoPP such as liver and kidney toxicity. Conclusions: Using the circulating monocytes in murine model of either I/R or MI as ‘shuttle bus', PLPs minized the need of relying on EPR effect in reaching the heart. Thus PLPs were demonstrated to be an effective delivery system in carrying CoPP to the infarct area, while minimizing the potential side-effects of the drug. Keywords: Drug delivery, MYOCARDIAL TISSUE, stimuli-response, Heart repair Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Tissue targeting nanoparticles Citation: Cheng B, Toh E, Chen E, Chang Y, Chau L, Chen P and Hsieh P (2016). Platelet-like proteoliposomes enable active drug delivery to infarcted heart tissue. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02026 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. 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Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Bill Cheng, Academia Sinica, Institute of Biomedical Science, Taipei, Taiwan, Email1 Dr. Elsie Toh, Academia Sinica, Institute of Biomedical Science, Taipei, Taiwan, elsietkw@gmail.com Dr. Egretta Chen, Academia Sinica, Institute of Biomedical Science, Taipei, Taiwan, kchen05@qub.ac.uk Dr. Yuan-Chih Chang, Academia Sinica, Institute of Cellular and Organismic Biology, Taipei, Taiwan, kondo@gate.sinica.edu.tw Dr. Lee-Young Chau, Academia Sinica, Institute of Biomedical Science, Taipei, Taiwan, lyc@ibms.sinica.edu.tw Dr. Peilin Chen, Academia Sinica, Research Center for Applied Sciences, Taipei, Taiwan, peilin@gate.sinica.edu.tw Dr. Patrick Hsieh, Academia Sinica, Institute of Biomedical Science, Taipei, Taiwan, phsieh@ibms.sinica.edu.tw Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bill Cheng Elsie Toh Egretta Chen Yuan-Chih Chang Lee-Young Chau Peilin Chen Patrick Hsieh Google Bill Cheng Elsie Toh Egretta Chen Yuan-Chih Chang Lee-Young Chau Peilin Chen Patrick Hsieh Google Scholar Bill Cheng Elsie Toh Egretta Chen Yuan-Chih Chang Lee-Young Chau Peilin Chen Patrick Hsieh PubMed Bill Cheng Elsie Toh Egretta Chen Yuan-Chih Chang Lee-Young Chau Peilin Chen Patrick Hsieh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.