Biodistribution of Poly(alkyl cyanoacrylate) Nanoparticles in Mice and Effect on Tumor Infiltration of Macrophages into a Patient-Derived Breast Cancer Xenograft
Abhilash D. Pandya,
Tore-Geir Iversen,
Siver Moestue,
Maria T. Grinde,
Ýrr Mørch,
Sofie Snipstad,
Andreas K. O. Åslund,
Geir F. Øy,
Wanja Kildal,
Olav Engebråten,
Kirsten Sandvig,
Tore Skotland,
Gunhild M. Mælandsmo
Affiliations
Abhilash D. Pandya
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Tore-Geir Iversen
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Siver Moestue
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Maria T. Grinde
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Ýrr Mørch
SINTEF AS, Department of Biotechnology and Nanomedicine, 7034 Trondheim, Norway
Sofie Snipstad
SINTEF AS, Department of Biotechnology and Nanomedicine, 7034 Trondheim, Norway
Andreas K. O. Åslund
SINTEF AS, Department of Biotechnology and Nanomedicine, 7034 Trondheim, Norway
Geir F. Øy
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Wanja Kildal
Institute for Cancer Genetics and Informatics, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Olav Engebråten
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Kirsten Sandvig
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Tore Skotland
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
Gunhild M. Mælandsmo
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway
We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in cellular responses in vitro. The PEBCA NPs had the highest uptake both in the patient-derived breast cancer xenograft MAS98.12 and in lymph nodes, and therefore, they are the most promising of these NPs for delivery of cancer drugs. High-resolution magic angle spinning magnetic resonance (HR MAS MR) spectroscopy did not reveal any differences in the metabolic profiles of tumors following injection of the NPs, but the PEBCA NPs resulted in higher tumor infiltration of the anti-tumorigenic M1 macrophages than obtained with the two other NPs. The PEBCA NPs also increased the ratio of M1/M2 (anti-tumorigenic/pro-tumorigenic) macrophages in the tumors, suggesting that these NPs might be used both as a vehicle for drug delivery and to modulate the immune response in favor of enhanced therapeutic effects.
