Synthesis of nanogels with controlled architecture via DE-ATRP for theranostic applications

Abstract

The recent advances in polymer production techniques, such as the deactivation-enhanced atom transfer radical polymerization (DE-ATRP), have been fundamental in the synthesis of architecture-controlled nanomaterials, especially in the development of advanced applications such as theranostics. Theranostic nanoplatforms (TNPs) integrate diagnostic and therapeutic applications into a single nanostructured complex. They have gained prominent attention due to their efficiency and specificity in combating dangerous diseases such as cancer. TNPs have great potential for clinical application, improving the drug bioavailability and the sensitivity of imaging techniques, consequently enhancing the treatment outcomes. To produce customized polymers, the DE-ATRP technique allows great control over the polymer size, molar mass, and dispersity, enabling the construction of materials with diverse and complex topologies. These mentioned parameters, along with aspects such as the solubility and composition of theranostic formulations, are of crucial importance in the development of nanoproducts safe for the patient and effective in combating the disease. In this context, hyper-branched copolymers and nanogels offer readily functionalizable platforms with intrinsic biocompatibility of great value for the development of new biomedical products. Thus, aiming at applications of controlled delivery of chemotherapeutic agents, as well as the monitoring and diagnosis of cancer, the present work proposes, in an unprecedented way, the development of hyper-branched nanogels, via DE-ATRP, composed mainly of myrcene, 2-dimethylaminoethyl methacrylate, and ethylene glycol dimethylacrylate. These nanoparticles will be loaded with paclitaxel, cisplatin, or other drugs, and embedded with iron oxide nanospheres, allowing them to be targeted specifically to diseased cells and visualized using magnetic resonance imaging. These nanoconjugates will also be evaluated for their in vitro toxicity with tumor cells in partnership with ICESP/FMUSP and FCFUSP. This project is being developed within the context of the thematic project FAPESP 2018/21489-1 and the PIPAE USP project "Multifunctional Hybrid Nanomaterials for Molecular Diagnosis and Theranostics (nanoTera)". (AU)