Investigation of Vascular Permeability and Diffusion Coefficient and Accumulation Changes in Time and Space of Nano-Drug Carriers in Mouse Tissues with Multiphoton Microscopy
Date Issued
2011
Date
2011
Author(s)
Liu, Han-Wen
Abstract
The goal of drug delivery in cancer chemotherapy is to kill tumor cell by maximal drug accumulation in tumor tissues. In order to reduce side effect in normal tissue, drug accumulation in normal tissue is the less the better. Exploiting the properties of high vascular permeability and lack of well-defined lymphatic system around tumors, drug can effectively extravasate and accumulate for a period of time in tumor tissues. How long and how much will the drug accumulate in tumor tissues depends on physical parameters such as plasma circulation half-life, vascular permeability, and diffusion coefficients in tumor tissues.
For in vivo measuring these parameters in a microscopic scale, in this thesis, we employed a nonlinear multi-photon microscopy and imaged the kinetics of drug carriers with fluorescent dextran. Vascular permeability, accumulation of dextran, and matrices diffusion constants are measured via melanoma mice ear tumor model. In early stage, we found vascular permeability increased due to the immune response. In mid-stage, vascular permeability decrease because of the end of immune response and the decreased vascular permeability makes lower concentration and accumulation in tumor tissue. In late stage, tumor induces more leaky vessels and the concentration and accumulation of drug accumulation in tumor tissues are increased.
Subjects
tumor
multiphoton nonlinear microscopy
accumulation
vascular permeability
diffusion coefficient
SDGs
Type
thesis
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