DEVELOPMENT OF NEW BI-DOTA COMPLEX-LOADED DENDRITIC POLYMER NANOPARTICLES FOR X-RAY IMAGING AND TREATMENT OF LUNG CANCER
Abstract
This research work covers the facile synthesis of a new sulfur-containing hyper-branched polyester polymer and its theranostic nano-platforms for the targeted optical, X-ray / computed tomography imaging and treatment of lung cancer (A549 Cells). To develop the proposed sulfur containing hyper branched polyester polymer an A2B-type monomer was designed. Sulfur was incorporated into the monomer by reacting diethylmalonate with 2-chloroethyl ethyl sulfide, resulting in a mono-thio-alkylated product. Further reaction with 4-bromobutyl acetate and subsequent hydrolysis resulted in the desired A2B monomer, 2-(4-hydroxy butyl)-2’-(2-ethyl ethyl sulfide) malonic acid. Solvent diffusion method was then used to fabricate polymeric nano platforms in water, capable of encapsulating optical dyes, contrast agents and therapeutic drugs in one-pot.
The overall hydrodynamic diameter of the formulated nano particles was found to be 82 nm using dynamic light scattering method. Surface carboxylic acid groups were conjugated with folic acid using water-based EDC/NHS chemistry, this allows for the targeted delivery of the cargos. The anticancer drug taxol encapsulating nano particles were able to target folate receptor expressing lung cancer cells (A549 cells) and more than 75% cell death was observed after 24 h of incubation. Interestingly, these polymeric nano particles exhibited enhanced X-ray contrast upon encapsulation with bismuth complexes (Bi-DOTA). The detailed optical and X-ray imaging, microscopic analysis, drug release kinetics and their potential theranostic applications are presented in this work.