Leukocyte Membrane Cloaked Carriers to Target and Overcome Tumor Vasculature

Methodist Hospital Research Institute, Houston TX

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Abstract

DESCRIPTION (provided by applicant): Cancer-induced inflammation represents a common feature that characterizes this disease independently from the tissues affected. Tumor microenvironment acquires peculiar differences from the physiological state that can enable specific targeting to the unhealthy site. Our body develops the ability to recognize and target inflammation through circulating white blood cells. This ability is very pronounced in cancer; a significant portion of the microenvironment is composed by infiltrating leukocytes. Nanomedicine came to forefront of cancer research in response to the rising needs to enhance drug targeting. Specifically, nanomedicine made possible the development of carriers adept at formulating drugs and providing a foundation available for the functionalization of targeted molecules in the hope of achieving selective accumulation within the tumor. Unfortunately, the biobarriers that regulate the defense mechanisms of our body from foreign agents also impede the delivery of nanocarriers attempting to target the tumor mass and thus limits their circulation and, effectively their clinical translation. Our efforts to create an efficient nano-based treatment were unsuccessful as our knowledge of the system was inadequate to face its complexity. Recently, we demonstrated that by using a bio-camouflaging approach we can synthesize hybrid, transendothelial migrating particles in vitro through the development of coatings derived from freshly isolated and purified infiltrating leukocyte cellular membranes. These Leukolike Vectors (LLV) combine the synergism of leukocyte qualities with the properties of nanocarriers. Aims- In order to evaluate the promise of this novel delivery platform in vivo, we intend to optimize our strategy through the following independent specific aims: 1) Improvement of LLV stability under shear stress forces, 2) Optimization and modulation of LLV coating quality 3) Evaluation of LLV therapeutic efficacy. Significance- The exploitation of the transfer of multiple leukocyte receptor in their active state on the particle's surface can increase the accumulation of the drug in the cancer microenvironment and decrease the side effects due to unspecific distribution. This study will set the foundation for the development of platforms capable of selectively targeting several types of tumors.