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Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma

Paper ID Volume ID Publish Year Pages File Format Full-Text
7164 537 2012 13 PDF Available
Title
Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma
Abstract

Multidrug resistance and cancer metastases are two obstacles to a successful chemotherapy and metastases are closely associated with drug resistance. Mitochondrial targeting topotecan-loaded liposomes have been developed to overcome this resistance and resistance-related metastases. Investigations were performed on breast cancer MCF-7 and resistant MCF-7/adr cells, MCF-7 and resistant MCF-7/adr tumor spheroids, resistant MCF-7/adr cell xenografts in nude mice, and a naturally resistant B16 melanoma metastatic model in nude mice. The mitochondrial targeting topotecan-loaded liposomes were approximately 64 nm in size, and exhibited the strongest inhibitory effects on MCF-7 cells and resistant MCF-7/adr cells. Mitochondrial targeting effects were demonstrated by co-localization in mitochondria, enhanced drug content in mitochondria, dissipated mitochondrial membrane potential, opening of mitochondrial permeability transition pores, release of cytochrome C, and activation of caspase 9 and 3. The targeting liposomes had a stronger inhibitory effect on the resistant tumor spheroids in vitro, enhanced accumulation in resistant MCF-7/adr cell xenografts in mice, as well as being very effective on resistant MCF-7/adr cell xenografts in mice, and having a marked anti-metastastic effect on the naturally resistant B16 melanoma metastatic model in mice. In conclusion, mitochondrial targeting topotecan-loaded liposomes could be a promising strategy for treating resistant cancers and resistance-related metastases.

Keywords
Mitochondrial targeting topotecan-loaded liposomes; Multidrug resistance; Metastases; Breast cancer; Melanoma
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Mitochondrial targeting topotecan-loaded liposomes for treating drug-resistant breast cancer and inhibiting invasive metastases of melanoma
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 6, February 2012, Pages 1808–1820
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us