Engineering lipid vesicles of enhanced intratumoral transport capabilities: Correlating liposome characteristics with penetration into human prostate tumor spheroids Journal Article

  

Authors:	Kostarelos, K.; Emfietzoglou, D.; Papakostas, A.; Yang, W. H.; Ballangrud, A. M.; Sgouros, G.
Article Title:	Engineering lipid vesicles of enhanced intratumoral transport capabilities: Correlating liposome characteristics with penetration into human prostate tumor spheroids
Abstract:	Liposomes have been widely used delivery systems, particularly relevant to the development of cancer therapeutics. Numerous liposome-based drugs are in the clinic or in clinical trials today against multiple tumor types; however, systematic studies of liposome interactions with solid or metastatic tumor nodules are scarce. This study is describing the in vitro interaction between liposomes and avascular human prostate (LNCaP-LN3) tumor spheroids. The ability offluorescently labelled liposomal delivery systems of varying physicochemical characteristics to penetrate within multicellular tumor spheroids has been investigated by confocal laser scanning microscopy. A variety of liposome characteristics and experimental parameters were investigated, including lipid bilayer composition, duration of liposome-spheroid interaction, mean liposome size, steric stabilization of liposomes. Electrostatic binding between cationic liposomes and spheroids was very efficient; however, it impeded any significant penetration of the vesicles within deeper layers of the tumor spheroid. Small unilamellar liposomes of neutral surface character did not bind as efficiently but exhibited enhanced penetrative transport capabilities closer to the tumor core. Polymer-coated (sterically stabilised) liposomes exhibited almost no interaction with the spheroid, indicating that their limited diffusion within avascular tissues may be a limiting step for their use against micrometastases. Multicellular tumor spheroids were used as models of solid tumor interstitium relevant to delivery systems able to extravasate from the microcapillaries or as models of prevascularized micrometastases. This study illustrates that interactions between liposomes and other drug delivery systems with mullicellular tumor spheroids can offer critically important information with respect to optimizing solid or micrometaslalic tumor delivery and targeting strategies. Copyright © Taylor & Francis Inc.
Keywords:	cancer chemotherapy; human cell; drug penetration; solid tumor; drug targeting; microscopy, electron; diffusion; fluorescent dye; tumor cells, cultured; prostatic neoplasms; prostate; prostate tumor; cell interaction; drug tumor level; multiple cancer; stereospecificity; drug binding; liposome; drug delivery system; confocal laser microscopy; liposomes; lipid bilayers; lipid bilayer; lipid vesicle; physical chemistry; phospholipids; drug delivery; spheroids, cellular; tumor spheroids; intratumoral transport; spheroid cell
Journal Title:	Journal of Liposome Research
Volume:	15
Issue:	1-2
ISSN:	0898-2104
Publisher:	Taylor & Francis Group
Date Published:	2005-03-01
Start Page:	15
End Page:	27
Language:	English
DOI:	10.1081/lpr-64953
PUBMED:	16194925
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-22144435165&partnerID=40&md5=35972ffc5d5a29ef56f49026fbbc31d7
Notes:	--- - "Cited By (since 1996): 15" - "Export Date: 24 October 2012" - "CODEN: JLREE" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/35316