Journal
BIOMACROMOLECULES
Volume 18, Issue 8, Pages 2489-2498Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.7b00629
Keywords
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Funding
- Excellence Initiative of the German federal and state governments
- START-program, Faculty of Medicine, RWTH Aachen University
- EU
- federal state of North Rhine-Westphalia [EFRE 30 00883 02]
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Development of nanosized drug delivery systems in cancer therapy is directed toward improving tumor selectivity and minimizing damages of healthy tissue. We introduce a delivery system with synergistic optimization and combination of passive and active targeting strategies. The approach is based on radiopeptide labeled redox sensitive hydrophilic nanogels, which exploit passive targeting by the enhanced permeability and retention effect while avoiding elimination by the mononuclear phagocyte system and fast hepatic and renal clearance. The targeting peptide promotes endocytotic uptake of the nanogels by cancer cells. Specific to this delivery system, tumor-specific degradation by the antioxidant glutathione enhances penetration and retention within the tumor tissue. Using in vivo molecular imaging we demonstrate the superiority of combined passive and active targeting with down-sizable nanogels over exclusive passive targeting. Furthermore, the homogeneous tumor distribution of functionalized nanogels compared to the clinically used mere radiopeptide supports the potentially high impact of our targeting concept.
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