Immunonanoparticles--an effective tool to impair harmful proteolysis in invasive breast tumor cells.
Breast cancer cells exhibit excessive proteolysis, which is responsible for extensive extracellular matrix degradation, invasion and metastasis. Besides other proteases, lysosomal cysteine protease cathepsin B has been implicated in these processes and the impairment of its intracellular activity was suggested to reduce harmful proteolysis and hence diminish progression of breast tumors. Here, we present an effective system composed of poly(D,L-lactide-coglycolide) nanoparticles, a specific anti-cytokeratin monoclonal IgG and cystatin, a potent protease inhibitor, that can neutralize the excessive intracellular proteolytic activity as well as invasive potential of breast tumor cells. The delivery system distinguishes between breast and other cells due to the monoclonal antibody specifically recognizing cytokeratines on the membrane of breast tumor cells. Bound nanoparticles are rapidly internalized by means of endocytosis releasing the inhibitor cargo within the lysosomes. This enables intracellular cathepsin B proteolytic activity to be inhibited, reducing the invasive and metastatic potential of tumor cells without affecting proteolytic functions in normal cells and processes. This approach may be applied for treatment of breast and other tumors in which intracellular proteolytic activity is a part of the process of malignant progression.
Faculty of Pharmacy, University of Ljubljana, Slovenia.
Natasa
N
Obermajer
Petra
P
Kocbek
Urska
U
Repnik
Alenka
A
Kuznik
Mateja
M
Cegnar
Julijana
J
Kristl
Janko
J
Kos
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D006868:Hydrolysis; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D020349:Surface Plasmon Resonance