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.
Highlights
Conventional anti-cancer agents used in chemotherapies do not demonstrate predominant tumor specificity compared to normal cells
Nanotechnology e.g., nanoparticle-based drug delivery, has emerged providing a more efficient targeting to tumors by passive accumulation which is known as the enhanced permeability and retention (EPR) effect [2]
The novelty of this work relies on investigating the effect of biological parameters of solid tumors, on magnetic targeting, which has only been studied in the context of passive tumor targeting to date
Summary
Conventional anti-cancer agents used in chemotherapies do not demonstrate predominant tumor specificity compared to normal cells. Cancer therapy is often terminated as a result of the severe side effects, caused by the therapeutic agents, before the expected therapeutic outcome is reached [1]. Nanotechnology e.g., nanoparticle-based drug delivery (nanomedicine), has emerged providing a more efficient targeting to tumors by passive accumulation which is known as the enhanced permeability and retention (EPR) effect [2]. A recent clinical study showed positive tumor accumulation of indium-111 radiolabeled PEGylated liposomes in 15 out of 17 patients employed [3]. The study hypothesized that the considerable heterogeneity in the EPR effect was likely due to the heterogeneous structural and functional integrity of the tumor neovasculature [3]
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