bm7b00629_si_001.pdf (968.65 kB)
Multistage Passive and Active Delivery of Radiolabeled Nanogels for Superior Tumor Penetration Efficiency
journal contribution
posted on 2017-07-06, 00:00 authored by Natascha Drude, Smriti Singh, Oliver H. Winz, Martin Möller, Felix M. Mottaghy, Agnieszka MorgenrothDevelopment
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.