Targeted non-covalent self-assembled nanoparticles based on human serum albumin.
Human serum albumin (HSA) is a biological nanocarrier that forms non-covalent complexes with a number of synthetic and biomolecules. Previously we demonstrated radiolabeled HSA-based nanoparticles can form non-covalent complexes with fluorescent cyanine dyes yielding imaging agents for surgical guidance towards tumor draining lymph nodes. Here the self-assembly approach enabled rapid clinical translation. Based on this experience we reasoned it would be interesting to expand this non-covalent technology to a targeted approach. Therefore, the ability of HSA to form non-covalent self-assembled complexes with peptides via near-infrared (NIR) cyanine dyes was explored. Föster resonance energy transfer (FRET) quenching interactions between HSA-Cy5 and the non-covalently bound fluorescent molecules indocyanine green (ICG), IR783-CO(2)H and three IR783-labeled targeting peptides were used to monitor complex assembly and disassembly. The host-guest interactions between HSA and IR783-labeled peptides enabled the formation of (bio)nanoparticles that are coated with peptides, which may target α(v)β(3)-integrins, the chemokine receptor 4 (CXCR4), or somatostatin receptors. The potential of CXCR4-targeted (bio)nanoparticles in sentinel lymph node procedures is demonstrated in vivo. By non-covalently binding NIR-dye labeled peptides to an already clinically approved HSA-scaffold, we have readily formed targeted bionanoparticles.
Division of Diagnostic Oncology, the Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.
Anton
A
Bunschoten
Tessa
T
Buckle
Joeri
J
Kuil
Gary D
GD
Luker
Kathryn E
KE
Luker
Omgo E
OE
Nieweg
Fijs W B
FW
van Leeuwen
D000818:Animals; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008962:Models, Theoretical; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
D010455:Peptides; D012709:Serum Albumin