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Core-Shell Chitosan Particles Targeting Membrane-Bound Heat Shock Protein 70 for Cancer Therapy
Elena V Svirshchevskaya1, Valentina V Kostenko1, Anna A Boyko1
1Laboratory of Cell Interactions, Department of Immunology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.
Abstract:
Anti-cancer targeted therapy is a promising approach. However, the identification of target molecules over-expressed in a wide range of tumors remains a significant challenge. The aim of this study was to analyze the expression of cell membrane-exposed heat shock protein 70 kDa (mHSP70) on different tumor cells and to develop a nanoscale delivery system based on a monoclonal antibody (mAb) that recognizes mHSP70 and uses chitosan core-shell nanoparticles (NPs). Several types of tumor cells (breast, pancreas, colon, prostate cancers, and some lymphomas) expressed mHSP70 as was determined by flow cytometry and confocal microscopy both in 2D and 3D cultures. Core NPs were formed by chitosan (C) conjugated to allocolchicinoid, which was used as a model drug (D). mAbs (A) targeting mHSP70 were complexed with succinylchitosan and used as NP shells forming final CAD-NPs. These NPs were characterized by size, charge, and functional activity. CAD-NPs were shown to have additional toxicity in comparison with CD-NPs in mHSP7-positive cells. Taken collectively, this study shows that mAb to mHSP70 can be used as a targeting vector in antitumor therapy.
Insights
Researchers developed targeted anti-cancer nanoparticles using a monoclonal antibody against cell membrane-exposed heat shock protein 70 kDa (mHSP70). These mHSP70-targeting nanoparticles show promise for delivering anti-cancer drugs specifically to tumor cells.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Targeted anti-cancer therapy requires identifying tumor-specific molecules.
- Cell membrane-exposed heat shock protein 70 kDa (mHSP70) is over-expressed on various cancer cells.
Purpose of the Study:
- To analyze mHSP70 expression on diverse tumor cells.
- To engineer mHSP70-targeting chitosan-based nanoparticles for drug delivery.
Main Methods:
- Flow cytometry and confocal microscopy assessed mHSP70 expression in 2D and 3D tumor cell cultures.
- Chitosan core nanoparticles (NPs) were conjugated with a model drug (allocolchicinoid).
- Monoclonal antibodies (mAbs) against mHSP70 formed the shell of the final nanoparticles (CAD-NPs).
Main Results:
- mHSP70 was detected on breast, pancreas, colon, and prostate cancer cells, as well as lymphomas.
- Characterization confirmed NP size, charge, and functionality.
- CAD-NPs exhibited enhanced toxicity against mHSP70-positive tumor cells compared to drug-loaded NPs without the antibody (CD-NPs).
Conclusions:
- Monoclonal antibodies targeting mHSP70 can serve as effective targeting vectors in anti-tumor therapy.
- mHSP70 is a viable target for developing targeted nanomedicine delivery systems.
- The developed CAD-NPs demonstrate potential for selective cancer treatment.
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