Investigating the Effect of Tumor Vascularization on Magnetic Targeting In Vivo Using Retrospective Design of Experiment

TY - JOUR

T1 - Investigating the Effect of Tumor Vascularization on Magnetic Targeting In Vivo Using Retrospective Design of Experiment

AU - Mei, Kuo-Ching

AU - Bai, Jie

AU - Lorrio, Silvia

AU - Tzu-Wen Wang , Julie

AU - Al-Jamal, Khuloud T.

PY - 2016/11

Y1 - 2016/11

N2 - 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.

AB - 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.

KW - enhanced permeability and retention

KW - immunohistochemistry

KW - nanocapsules

KW - nanomedicine

KW - superparamagnetic iron oxide nanoparticles

UR - https://www.scopus.com/pages/publications/84983795647

U2 - 10.1016/j.biomaterials.2016.08.030

DO - 10.1016/j.biomaterials.2016.08.030

M3 - Article

SN - 0142-9612

VL - 106

SP - 276

EP - 285

JO - Biomaterials

JF - Biomaterials

ER -