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Remya Valsalakumari,1– 3 Abhilash D Pandya,3,* Lina Prasmickaite,3,* Audun Kvalvaag,1,2 Anne Grethe Myrann,1,2 Andreas KO Åslund,4 Marianne Steinsvik Kjos,4 Cristina Fontecha-Cuenca,5,6 Hajira B Haroon,5 Ana RS Ribeiro,7 Jutta Horejs-Hoeck,7,8 S Moein Moghimi,5,9,10 Ýrr Mørch,4 Tore Skotland,1,2 Kirsten Sandvig,1,2,11 Gunhild Mari Mælandsmo,3,12 Tore Geir Iversen1,2 1Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, 0379, Norway; 2Centre for Cancer Cell Reprogramming, University of Oslo, Oslo, 0379, Norway; 3Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, 0379, Norway; 4Department of Biotechnology and Nanomedicine, SINTEF AS, Trondheim, 7034, Norway; 5School of Pharmacy, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK; 6Department of Biomedical Science, University of Padova, Padova, Italy; 7Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, 5020, Austria; 8Cancer Cluster Salzburg, Salzburg, 5020, Austria; 9Faculty of Health and Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 10Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Center, Aurora, CO, USA; 11Department of Biosciences, University of Oslo, Oslo, 0316, Norway; 12Department of Medical Biology, University of Tromsø, Tromsø, 9019, Norway*These authors contributed equally to this workCorrespondence: Tore Geir Iversen, Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, 0379, Norway, Tel +47 22781826, Email t.g.iversen@ous-research.noBackground: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We

The complement system, professional phagocytes and other cells such as Natural killer cells and mast cells are among the important components of the innate arm of the immune system. These constituents provide an orchestrated array of defences and responses against tissue injury and foreign particles, including nanopharmaceuticals. While interception of nanopharmaceuticals by the immune system is beneficial for immunomodulation and treatment of phagocytic cell disorders, it is imperative to understand the multifaceted mechanisms by which nanopharmaceuticals interacts with the immune system and evaluate the subsequent balance of beneficial versus adverse reactions. An example of the latter is adverse infusion reactions to regulatory-approved nanopharmaceuticals seen in human subjects. Here, we discuss collective opinions and findings from our laboratories in mapping nanoparticle-mediated complement and leucocyte/macrophage responses.

Nonlamellar lyotropic liquid crystalline (LLC) nanoparticles are a family of versatile nano-self-assemblies, which are finding increasing applications in drug solubilization and targeted drug delivery. LLC nanodispersions are heterogeneous with discrete nanoparticle subpopulations of distinct internal architecture and morphology, frequently coexisting with micelles and/or vesicles. Diversity in the internal architectural repertoire of LLC nanodispersions grants versatility in drug solubilization, encapsulation, and release rate. However, drug incorporation contributes to the heterogeneity of LLC nanodispersions, and on exposure to biological media, LLC nanodispersions often undergo nanostructural and morphological transformations. From a pharmaceutical perspective, coexistence of multiple types of nanoparticles with diverse structural attributes, together with media-driven transformations in colloidal characteristics, brings challenges in dissecting biological and therapeutic performance of LLC nanodispersions in a spatiotemporal manner. Here, we outline innate and acquired heterogeneity of LLC nanodispersions and discuss technological developments and alternative approaches needed to improve homogeneity of LLC formulations for drug delivery applications.