Selective Targeting of Tumor and Stromal Cells By a Nanocarrier System Displaying Lipidated Cathepsin B Inhibitor

Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC‐NS‐629) is described. Ex vivo and in vivo studie...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2014-09, Vol.53 (38), p.10077-10081
Main Authors: Mikhaylov, G., Klimpel, D., Schaschke, N., Mikac, U., Vizovisek, M., Fonovic, M., Turk, V., Turk, Boris, Vasiljeva, Olga
Format: Article
Language:English
Subjects:
Animals
cancer
Cathepsin B - antagonists & inhibitors
Cathepsin B - metabolism
cathepsin B
Cell Line, Tumor
Cell Survival - drug effects
Cell Transformation, Neoplastic - drug effects
Cell Transformation, Neoplastic - pathology
Communications
Cysteine Proteinase Inhibitors - chemical synthesis
Cysteine Proteinase Inhibitors - chemistry
Cysteine Proteinase Inhibitors - pharmacology
Dose-Response Relationship, Drug
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Carriers - chemistry
drug delivery
Drug Delivery Systems
Female
Mammary Neoplasms, Experimental - diagnosis
Mammary Neoplasms, Experimental - drug therapy
Mice
Molecular Structure
Nanostructures - chemistry
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - pathology
Structure-Activity Relationship
theranostics
tumor microenvironment
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Summary:Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC‐NS‐629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC‐NS‐629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment. On target: A lipidated cathepsin B (CtsB) inhibitor was incorporated into the envelope of a liposomal nanocarrier. The resulting CtsB‐targeted drug delivery system, which can be loaded with diagnostic or therapeutic agents, was selectively internalized by tumor and stromal cells, thus validating CtsB targeting as a promising approach to cancer diagnosis and treatment.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201402305