Abstract Title

A Bioinformatics Approach to the Design and Engineering of Biomimetic Personalized Nanoparticle Therapy for Bone Metastatic Prostate Cancer

Presenter Name

Andrew Gdowski

RAD Assignment Number

315

Abstract

Purpose: Bone metastatic prostate cancer remains a challenge to treat clinically due to lack of therapies prolonging overall survival and off target side effects of current treatments. In this study, we employ a bioinformatics approach for target validation and design of biomimetic cancer-coated nanoparticles (CCNP) for treatment of bone metastatic prostate cancer. Our goal is to personalize this targeted therapy by utilizing a patient’s own cancer cells to coat the nanoparticles. We hypothesize that this approach will be an effective strategy to deliver drugs to the site of metastasis.

Methods: A bone metastatic prostate cancer target was identified utilizing The Cancer Genome Atlas (TCGA) database from a study of 130 patients with metastatic prostate cancer who underwent next-generation sequencing of their tumors. We used this information and stimulated prostate cancer cells to increase expression of this targeted cell membrane protein. These membranes where purified and used to coat nanoparticles. Nanoparticles were characterized with TEM, DLS, and zeta potential. Membrane purification was validated with coommassie stain and western blot. Membrane orientation on nanoparticle surface was verified with an immuno-conjugation assay. Nanoparticle cancer cell uptake was quantified through immunofluorescence and flow cytometry. Cell viability was performed with MTT assay.

Results: Nanoparticles were successfully coated with stimulated cancer cell membranes. Nanoparticle size and zeta potential both increased after coating with membrane. After membrane purification, only markers for cell membranes were identified. Immuno-conjugation assay demonstrated that the cell membrane coating was correctly oriented on the nanoparticle surface. Immunofluorescence results showed when nanoparticles were coated with the cell membrane, there was increased nanoparticle uptake. This was verified by flow cytometry. Stimulated nanoparticles showed decreased cell viability in MTT assay.

Conclusions: We successfully engineered cancer coated nanoparticles and validated the manufacturing process. This novel approach to target identification and personalized coating of nanoparticles has tremendous potential as a strategy for treating bone metastasis in prostate cancer patients. Future experiments will study in vivo targeting of bone metastatic lesions with these biomimetic nanoparticles.

Research Area

Cancer

Presentation Type

Poster

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A Bioinformatics Approach to the Design and Engineering of Biomimetic Personalized Nanoparticle Therapy for Bone Metastatic Prostate Cancer

Purpose: Bone metastatic prostate cancer remains a challenge to treat clinically due to lack of therapies prolonging overall survival and off target side effects of current treatments. In this study, we employ a bioinformatics approach for target validation and design of biomimetic cancer-coated nanoparticles (CCNP) for treatment of bone metastatic prostate cancer. Our goal is to personalize this targeted therapy by utilizing a patient’s own cancer cells to coat the nanoparticles. We hypothesize that this approach will be an effective strategy to deliver drugs to the site of metastasis.

Methods: A bone metastatic prostate cancer target was identified utilizing The Cancer Genome Atlas (TCGA) database from a study of 130 patients with metastatic prostate cancer who underwent next-generation sequencing of their tumors. We used this information and stimulated prostate cancer cells to increase expression of this targeted cell membrane protein. These membranes where purified and used to coat nanoparticles. Nanoparticles were characterized with TEM, DLS, and zeta potential. Membrane purification was validated with coommassie stain and western blot. Membrane orientation on nanoparticle surface was verified with an immuno-conjugation assay. Nanoparticle cancer cell uptake was quantified through immunofluorescence and flow cytometry. Cell viability was performed with MTT assay.

Results: Nanoparticles were successfully coated with stimulated cancer cell membranes. Nanoparticle size and zeta potential both increased after coating with membrane. After membrane purification, only markers for cell membranes were identified. Immuno-conjugation assay demonstrated that the cell membrane coating was correctly oriented on the nanoparticle surface. Immunofluorescence results showed when nanoparticles were coated with the cell membrane, there was increased nanoparticle uptake. This was verified by flow cytometry. Stimulated nanoparticles showed decreased cell viability in MTT assay.

Conclusions: We successfully engineered cancer coated nanoparticles and validated the manufacturing process. This novel approach to target identification and personalized coating of nanoparticles has tremendous potential as a strategy for treating bone metastasis in prostate cancer patients. Future experiments will study in vivo targeting of bone metastatic lesions with these biomimetic nanoparticles.