(315c) Award Submission: Nanoparticle Carrying T Cells for Targeted Drug Delivery

Authors: 
Abedin, M. R. - Presenter, Missouri University of Science and Technology
Liu, Y., Mallinckrodt Institute of Radiology, Washington University School of Medicine
Barua, S., Missouri University of Science and Technology

Abedin, Muhammad (S&T-Student) Normal Abedin, Muhammad (S&T-Student) 2 0 2019-04-12T04:35:00Z 2019-04-12T04:35:00Z 1 508 2901 Missouri University of Science and Technology 24 6 3403 15.00

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text-align:center;line-height:19.2pt;background:white">Bionanotechnology (22B 01)

text-align:center;line-height:19.2pt;background:white"> normal"> " times new roman>Award Submission: Nanoparticle
Carrying T Cells for Targeted Drug Delivery

text-align:center;line-height:19.2pt;background:white">Muhammad Raisul Abedina, Yongjian Liub, Sutapa Baruaa,1

text-align:center;line-height:19.2pt;background:white">a Department of Chemical and Biochemical
Engineering, Missouri University of Science and Technology,

text-align:center;line-height:19.2pt;background:white">Rolla, MO-65409

text-align:center;line-height:19.2pt;background:white"> b Mallinckrodt Institute of Radiology, Washington
University School of Medicine, Washington University    in St. Louis, St. Louis, MO-63110

text-align:center;line-height:19.2pt;background:white">1 10.0pt;font-family:" times new roman color:>Corresponding Author: Email: baruas@mst.edu

text-align:center;line-height:19.2pt;background:white">

normal">Abstract

normal">

justify"> line-height:107%;font-family:" times new roman>Objective

mso-add-space:auto;text-align:justify;line-height:normal">The overall goal
of this article is to explore a combinatorial approach in exploiting the
specificity of antibody conjugated drug nanorods with the direction of
polyclonal T cells for breast cancer therapy. We hypothesize that the
attachment of Trastuzumab-conjugated paclitaxel drug nanorods to natural T
cells will enhance their circulation time and substantially alter their
anti-tumoral efficacy.

mso-add-space:auto;text-align:justify;line-height:normal">

justify"> line-height:107%;font-family:" times new roman>Introduction

auto;text-align:justify;line-height:normal"> mso-bidi-font-size:11.0pt;font-family:" times new roman>Major
limitations of the current nano drug delivery vehicles are inefficient
transport of drug to the tumor site, uncontrolled nanoparticle-biomolecule
interaction at the extra cellular matrix, and intracellular lysosomal or
phagolysosomal degradation of the nanoparticle.
Moreover, the majority of the designed
nano drug vehicles accumulate in the vicinity of the off target cells or
tissues resulting in off target toxicity or might be eliminated by the residing
macrophages in the organs like liver and spleens. To address this
issue, this project aims to take a combinatorial approach of immunotherapies,
and targeted drug NPs for efficient
delivery of therapeutic payloads to the breast cancer site, and expand
therapeutic benefits. Here, we propose an alternative strategy that makes use
of the ability of natural immune T cells to circulate and target breast cancer
cells for the effective delivery of synthetic drug NPs. Specifically, it is
proposed to anchor Trastuzumab conjugated paclitaxel drug nanorods to the
surface of patient derived T cells as a means of avoiding the reticuloendothelial
system (RES) clearance. We hypothesize that the attachment of
Trastuzumab-conjugated paclitaxel drug nanorods to natural T cells will enhance
their circulation time and substantially alter their anti-tumoral efficacy.

justify">

justify"> line-height:107%;font-family:" times new roman>Materials and Methods

justify"> 107%;font-family:" times new roman>Paclitaxel nanorods (503.42±210
nm) 107%;font-family:" times new roman>were prepared using the solvent diffusion method. Trastuzumab (TTZ) (Genentech)
was conjugated with the functionalized paclitaxel drug nanorods. The antibody
drug conjugate (PTXNR-TTZ) was further conjugated with the DOTA chelator for
radiolabeling with positron emitting 64Cu isotope. Cytotoxic T lymphocytes
were bound with PTXNR-TTZ in serum free un-supplemented RPMI 1640 medium. normal">

justify"> line-height:107%;font-family:" times new roman>

justify"> line-height:107%;font-family:" times new roman>Results

justify"> 107%;font-family:" times new roman>The SEM images confirm
the cylindrical or rod-like the shape of the paclitaxel drug particles in the
nano dimension of (503.42±210) 18.0pt;line-height:107%;font-family:" times new roman text1>× ( mso-bidi-font-size:11.0pt;line-height:107%;font-family:" times new roman mso-no-proof:yes>96.87±33)nm. The nanoparticle synthesis efficiency was 65%. Monoclonal
antibody trastuzumab was chemically conjugated with the paclitaxel drug nanorods
with the conjugation efficiency of  53%.
The drug NRs along with the antibody conjugated PTXNR-TTZ showed enhanced
stability in the biological media. PTXNR-TTZ was bound on the surface of the
cytotoxic T lymphocytes without inducing apoptosis to the T cells. T- cell
surface bound antibody conjugated drug nanorods induced apoptosis in HER 2+
breast cancer cells resulting in significant tumor clearence.