Large anti-HER2/neu liposomes for potential targeted intraperitoneal therapy of micrometastatic cancer Journal Article
| Authors: | Sofou, S.; Enmon, R.; Palm, S.; Kappel, B.; Zanzonico, P.; McDevitt, M. R.; Scheinberg, D. A.; Sgouros, G. |
| Article Title: | Large anti-HER2/neu liposomes for potential targeted intraperitoneal therapy of micrometastatic cancer |
| Abstract: | Effective targeting and killing of intraperitoneally disseminated micrometastases remains a challenge. Objective/Methods:In this work, we evaluated the potential of antibody-labeled PEGylated large liposomes as vehicles for direct intraperitoneal (i.p.) drug delivery with the aim to enhance the tumor-to-normal organ ratio and to improve the bioexposure of cancer cells to the delivered therapeutics while shifting the toxicities toward the spleen. These targeted liposomes are designed to combine: (1) specific targeting to and internalization by cancer cells mediated by liposome-conjugated tumor-specific antibodies, (2) slow clearance from the peritoneal cavity, and (3) shift of normal organ toxicities from the liver to the spleen due to their relatively large size. Results:Conjugation of anti-HER2/neu antibodies to the surface of large (approximately 600nm in diameter) PEGylated liposomes results in fast, specific binding of targeted liposomes to cancer cells in vitro, followed by considerable cellular internalization. In vivo, after i.p. administration, these liposomes exhibit fast, specific binding to i.p. cancerous tumors. Large liposomes are slowly cleared from the peritoneal cavity, and they exhibit increased uptake by the spleen relative to the liver, while targeted large liposomes demonstrate specific tumor uptake at early times. Although tissue and tumor uptake are greater for cationic liposomes, the tumor-to-liver and spleen-to-liver ratios are similar for both membrane compositions, suggesting a primary role for the liposome's size, compared to the liposome's surface charge. Conclusions:The findings of this study suggest that large targeted liposomes administered i.p. could be a potent drug-delivery strategy for locoregional therapy of i.p. micrometastatic tumors. © 2010 Informa Healthcare USA, Inc. |
| Keywords: | treatment outcome; treatment response; human cell; nonhuman; drug targeting; neoplasms; ovarian cancer; mouse; animals; mice; epidermal growth factor receptor 2; animal experiment; cancer cell culture; in vitro study; mice, inbred balb c; drug delivery systems; mice, nude; ovary carcinoma; neoplasm metastasis; receptor, erbb-2; tumor growth; trastuzumab; biocompatible materials; drug tumor level; antibodies, neoplasm; drug conjugation; infusions, parenteral; liposome; drug delivery system; particle size; liposomes; encapsulation; internalization; drug carriers; antibody labeling; surface charge; intraperitoneal therapy; large liposomes; targeted liposomes; calcein; light scattering; peritoneal cavity; materials testing |
| Journal Title: | Journal of Liposome Research |
| Volume: | 20 |
| Issue: | 4 |
| ISSN: | 0898-2104 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2010-12-01 |
| Start Page: | 330 |
| End Page: | 340 |
| Language: | English |
| DOI: | 10.3109/08982100903544185 |
| PUBMED: | 20070139 |
| PROVIDER: | scopus |
| PMCID: | PMC3172685 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: JLREE" - "Source: Scopus" |
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