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Dual Functional Liposomes for Improved Cancer Cell Targeting and Enhanced Intracellular Delivery.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Dual Functional Liposomes for Improved Cancer Cell Targeting and Enhanced Intracellular Delivery./
作者:	Deshpande, Pranali Prabhakar.
面頁冊數:	1 online resource (150 pages)
附註:	Source: Dissertations Abstracts International, Volume: 79-10, Section: B.
Contained By:	Dissertations Abstracts International79-10B.
標題:	Pharmaceutical sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10259198click for full text (PQDT)
ISBN:	9780355772838

Dual Functional Liposomes for Improved Cancer Cell Targeting and Enhanced Intracellular Delivery.
Deshpande, Pranali Prabhakar.

Dual Functional Liposomes for Improved Cancer Cell Targeting and Enhanced Intracellular Delivery. - 1 online resource (150 pages)

Source: Dissertations Abstracts International, Volume: 79-10, Section: B.

Thesis (Ph.D.)--Northeastern University, 2017.

Includes bibliographical references

Cancer therapy has undergone remarkable changes in recent times making great progress. However, there still remains an unmet need to completely cure cancer. A major limitation of cancer therapy is the undesired effects on non-target tissues. Using targeted nanocarriers like liposomes can help to enhance delivery of therapeutics to a pathological area, influence the pharmacokinetic profile of the drug and enhance its accumulation in the targeted sites. Modification of the liposome surface is critical for control of liposomal properties and therefore, their biological behavior. Polyethylene glycol (PEG)-modified liposomes have enhanced longevity in blood by escaping clearance by the reticulo-endothelial system (RES), resulting in increased accumulation at the tumor sites via passive targeting owing to the enhanced permeability and retention (EPR) effect. In this study, we took advantage of passive, active and intra-cellular targeting capabilities of liposomes for cancer therapy by modifying their surface with ligands. PEG coated DOX-loaded liposomes were surface-modified with an intracellular delivery agent, octa-arginine (R8) peptide, to facilitate improved cytosolic delivery of DOX. R8 was attached to the distal end of the PEG chain, in a polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based amphiphilic polymer for conjugation with the liposome bilayer and improved access to its site of cellular interaction. Once the R8-coated DOX-loaded liposomes entered the tumor tissue by passive targeting, the exposed R8 was expected to bring about intracellular penetration of the liposomes and cytosolic delivery of DOX. Cellular uptake of these liposomes studied by confocal microscopy and flow cytometry in cancer cells in vitro, highlighted advantages of R8 as a tool for intracellular delivery of the payload, compared to the unmodified liposomes. R8-modified liposomes illustrated superior effects in terms of in vitro cytotoxicity and apoptosis and good tumor growth inhibition in vivo. However, the interaction of R8-liposomes with cancer cells is non-specific. To make the formulation cancer cell-targeted, a second ligand was added to the liposome surface. Dual functional liposomes (DualL) were prepared by modification of liposome-surface with transferrin molecules, in combination with the R8-modification, to target the transferrin receptors (TfRs) that are known to be over-expressed on the surface of many cancer cells. Fluorescently labelled DualL, without the DOX payload, were tested for their interactions with TfR over-expressing A2780 ovarian cancer cells. Flow cytometry and confocal microscopy, clearly indicated better association and internalization of DualL versus R8L, pointing to the involvement of both ligands in these effects. When loaded with DOX, Dual DOX-L showed augmented selective cytotoxicity towards cancer cells versus non-cancer cells in vitro. Cytotoxicity of R8 DOX-L was equivalent in the tested cancer and non-cancer cell lines presenting proof of their non-specificity towards cancer cells. The therapeutic potential of Dual DOX-L was tested in vivo in an A2780 ovarian xenograft model in nude mice. In tumor-bearing mice, higher distribution and accumulation of DOX in tumors was obtained upon i.v. administration of Dual DOX-L compared to other treatment groups. A tumor growth inhibition study demonstrated a clear pattern of suppression in tumor growth for Dual DOX-L treated tumors along the course of treatment. On the whole, these results favor the idea of modification of liposome-surfaces with combinations of ligands that have properties of both cancer-cell targeting and improved intracellular delivery to enhance efficacy of their payloads for cancer therapy.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9780355772838Subjects--Topical Terms:

3173021
Pharmaceutical sciences.
Subjects--Index Terms:

CancerIndex Terms--Genre/Form:

542853
Electronic books.

Dual Functional Liposomes for Improved Cancer Cell Targeting and Enhanced Intracellular Delivery.
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