title: Investigating the effect of tumor vascularization on magnetic targeting in vivo using retrospective design of experiment.
abstract: Nanocarriers take advantages of the enhanced permeability and retention (EPR) to accumulate passively in solid tumors. Magnetic targeting has shown to further enhance tumor accumulation in response to a magnetic field gradient. It is widely known that passive accumulation of nanocarriers varies hugely in tumor tissues of different tumor vascularization. It is hypothesized that magnetic targeting is likely to be influenced by such factors. In this work, magnetic targeting is assessed in a range of subcutaneously implanted murine tumors, namely, colon (CT26), breast (4T1), lung (Lewis lung carcinoma) cancer and melanoma (B16F10). Passively- and magnetically-driven tumor accumulation of the radiolabeled polymeric magnetic nanocapsules are assessed with gamma counting. The influence of tumor vasculature, namely, the tumor microvessel density, permeability and diameter on passive and magnetic tumor targeting is assessed with the aid of the retrospective design of experiment (DoE) approach. It is clear that the three tumor vascular parameters contribute greatly to both passive and magnetically targeted tumor accumulation but play different roles when nanocarriers are targeted to the tumor with different strategies. It is concluded that tumor permeability is a rate-limiting factor in both targeting modes. Diameter and microvessel density influence passive and magnetic tumor targeting, respectively.
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
authors: Kuo-Ching
authors: KC
authors: Mei
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
authors: Jie
authors: J
authors: Bai
authors: Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, SE1 7EH, United Kingdom.
authors: Silvia
authors: S
authors: Lorrio
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
authors: Julie Tzu-Wen
authors: JT
authors: Wang
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors: Khuloud T
authors: KT
authors: Al-Jamal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003911:Dextrans / Q000097:blood* / Q000528:radiation effects*; D058185:Magnetite Nanoparticles / Q000528:radiation effects*; D051379:Mice; D055806:Microvessels / Q000737:chemistry* / Q000473:pathology / Q000528:radiation effects; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000737:chemistry* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology*; D014018:Tissue Distribution
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
keywords: Enhanced permeability and retention; Immunohistochemistry; Nanocapsules; Nanomedicine; Superparamagnetic iron oxide nanoparticles