Stimuli-responsive conjugated polymer nanoparticles as simple theranostic platforms = Basit teranostik platformlar olarak uyaranlara hassas konjuge polimer nanoparçacıklar

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.