(675d) Nanoparticle Hitchhiked T Cells for Targeted Drug Delivery
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Materials Engineering and Sciences Division
Biomaterials for Drug Delivery: Particles & Colloids
Thursday, November 14, 2019 - 1:24pm to 1:42pm
Abedin, Muhammad (S&T-Student) Normal Abedin, Muhammad (S&T-Student) 2 2498 2019-04-12T03:37:00Z 2019-04-12T03:37:00Z 1 497 2837 Missouri University of Science and Technology 23 6 3328 15.00
Clean Clean false false false EN-US X-NONE X-NONE H4sIAAAAAAAEAKtWckksSQxILCpxzi/NK1GyMqwFAAEhoTITAAAA H4sIAAAAAAAEAKtWcslP9kxRslIyNDa0tDAysjQ2szAxNzExsDBX0lEKTi0uzszPAykwrQUAst4nCywAAAA=
text-align:center;line-height:19.2pt;background:white">Biomaterials (08B 05)
text-align:center;line-height:19.2pt;background:white">
normal">
" times new roman>Nanoparticle Hitchhiked
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">
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 will have better accessibility to the complex tumor microenvironment. The
cellular vehicle could substantially alter their anti-tumoral
efficacy and hence be an efficient biocompatible system for therapeutic drug
delivery. 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"> font-family:" times new roman>Our current study 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. 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. 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 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. 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> 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%. Paclitaxel
nanorods were chemically activated using carbonyldiimidazole and conjugated to
monoclonal antibody trastuzumab 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.
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">We explore acombinatorial 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 will have better accessibility to the complex tumor microenvironment. The
cellular vehicle could substantially alter their anti-tumoral
efficacy and hence be an efficient biocompatible system for therapeutic drug
delivery. 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"> font-family:" times new roman>Our current study 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. 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. 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 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. 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> 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%. Paclitaxel
nanorods were chemically activated using carbonyldiimidazole and conjugated to
monoclonal antibody trastuzumab 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.