3 years ago

Multistage Passive and Active Delivery of Radiolabeled Nanogels for Superior Tumor Penetration Efficiency

Multistage Passive and Active Delivery of Radiolabeled Nanogels for Superior Tumor Penetration Efficiency
Martin Möller, Natascha Drude, Felix M. Mottaghy, Smriti Singh, Agnieszka Morgenroth, Oliver H. Winz
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.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00629

DOI: 10.1021/acs.biomac.7b00629

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