Stimuli-responsive conjugated polymer nanoparticles as simple theranostic platforms = Basit teranostik platformlar olarak uyaranlara hassas konjuge polimer nanoparçacıklar
Author
Özgün, Alp
Advisor
Tuncel, Dönüş
Date
2014Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
In this study, green and near-infrared emitting stimuli responsive conjugated polymer
nanoparticles that can be utilized simultaneously for chemotherapeutic drug delivery and
bioimaging were synthesized. The nanoparticles are sensitive to low pH values of tumor
microenvironment or elevated redox potential of some tumor types. These theranostic platforms
could be used for in-vivo imaging and perform controlled-drug release triggered by an
appropriate stimulus.
For this purpose, green emitting polymer with fluorene and benzothiadiazole alternating units
in the backbone and a conjugated polymer emitting in the red-NIR region based on thiophene
and benzothiadiazole alternating units in the backbone were synthesized and characterized.
Nanoparticles of these polymers (CPNs) were prepared by a simple method called
nanoprecipitation where hydrophobic polymer chains collapse onto each other in aqueous
media, trapping any other hydrophobic drug molecules (anticancer agent camptothecin in our
case) in the environment inside the polymer matrix. Nanoprecipitation process was optimized
for each polymer to obtain maximum drug encapsulation rate and a narrow nanoparticle size
distribution under 100 nm. Resulting CPNs were stable for a long time in PBS buffer, water,
bovine serum albumin and human plasma. SEM images showed spherical particles with a
narrow diameter distribution. In vitro drug release studies, pH responsive CPNs showed faster
drug release in more acidic media. Redox sensitive red polymer on the other hand showed a
cleavage of disulfide bond in its structure in the presence of stimulus.
To evaluate the cytotoxicity of drug loaded and blank CPNs RT-CES (real-time cell electronic
sensing) assays with HuH-7 cell line have been carried out. While blank CPNs show an
insignificant temporary cytotoxicity, camptothecin loaded nanoparticles match or outperform
the growth inhibition effect of free camptothecin. Fluorescence microscopy images of HuH-7
cells incubated with CPNs clearly show CPNs that are internalized by cells. In conclusion, it was demonstrated that conjugated polymers could be used to fabricate
theranostic platforms without the need for an additional imaging agent and their structures can
be engineered to obtain stimuli responsive smart drug delivery systems. These results promise
simple and easily fabricated smart systems that can selectively carry anticancer agents to
tumors while enabling monitoring of drug distribution and inexpensive tumor imaging without
using any harmful rays on the highly energetic side of the electromagnetic spectrum.