Program
Chemical and Biological Engineering
College
Engineering
Student Level
Doctoral
Location
PAÍS Building
Start Date
10-11-2022 11:00 AM
End Date
10-11-2022 1:00 PM
Abstract
The use of exogenous siRNA technology to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for treatment of diseases such as prostate cancer (PC). The promise of siRNA-based therapeutics is dependent on the development of platforms that effectively protect siRNA from nuclease degradation and deliver the siRNA to the cytosol of target cells. The establishment of nanoparticle-based siRNA delivery platforms have been investigated to mitigate the cost and safety issues associated with viral delivery platforms. In this work, we present the development and characterization of a lipid coated mesoporous silica nanoparticle (LC-MSN) to address the need for safe and effective siRNA delivery across various biological barriers in the relapsed prostate cancer landscape. The LC-MSN utilizes calcium silicate nanogating over the silica core to efficiently load (80%) and release (>80%) siRNA in relevant media, as analyzed by tracking a fluorescently tagged siRNA cargo. Additionally, the calcium silicate core is encapsulated in a lipid bilayer aimed to improve the LC-MSN biocompatibility and enables the integration of GRP78 minibodies for targeted delivery to PC cells. The cytotoxicity, uptake and intracellular fate of the LC-MSN is investigated within our work using the LNCaP PC cell line. Furthermore, our work utilizes an ex ovo chick chorioallantoic membrane model (CAM) to assess LC-MSN system vascular margination, binding, circulation time and stability. The structural and chemical versatility of the silica nanoparticle core along with a biocompatible lipid coating makes the LC-MSN a promising candidate for siRNA delivery within the relapsed PC landscape.
Rational Design of Silica-Based Nanoparticles for Overcoming Barriers of siRNA Delivery in Relapsed Prostate Cancer Applications
PAÍS Building
The use of exogenous siRNA technology to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for treatment of diseases such as prostate cancer (PC). The promise of siRNA-based therapeutics is dependent on the development of platforms that effectively protect siRNA from nuclease degradation and deliver the siRNA to the cytosol of target cells. The establishment of nanoparticle-based siRNA delivery platforms have been investigated to mitigate the cost and safety issues associated with viral delivery platforms. In this work, we present the development and characterization of a lipid coated mesoporous silica nanoparticle (LC-MSN) to address the need for safe and effective siRNA delivery across various biological barriers in the relapsed prostate cancer landscape. The LC-MSN utilizes calcium silicate nanogating over the silica core to efficiently load (80%) and release (>80%) siRNA in relevant media, as analyzed by tracking a fluorescently tagged siRNA cargo. Additionally, the calcium silicate core is encapsulated in a lipid bilayer aimed to improve the LC-MSN biocompatibility and enables the integration of GRP78 minibodies for targeted delivery to PC cells. The cytotoxicity, uptake and intracellular fate of the LC-MSN is investigated within our work using the LNCaP PC cell line. Furthermore, our work utilizes an ex ovo chick chorioallantoic membrane model (CAM) to assess LC-MSN system vascular margination, binding, circulation time and stability. The structural and chemical versatility of the silica nanoparticle core along with a biocompatible lipid coating makes the LC-MSN a promising candidate for siRNA delivery within the relapsed PC landscape.
