Nanosized theranostic agent based on PEGylated branched polylactide modified with gadolinium (III) oxide for doxorubicin cancer treatment and MRI diagnostics

Treating and diagnosing drug-resistant tumors is an important challenge for rapidly developing nanomedicine. The new polymer-inorganic 10–15 nm nanoparticles based on branched PEGylated polylactide macromolecules with a number-average molecular weight of 14,200 modified with gadolinium (III) oxide offer a promising solution. The advantage of using PEGylated branched polylactides compared to traditional linear block copolymers is the suppression of micelle formation, which allows significantly reducing the theranostic’s particle size. The structure of the nanosized carrier is characterized by 1H NMR, 13C NMR, IR spectroscopy, and XRD, and the expected size of nanoparticles is estimated theoretically and determined experimentally by TEM and SAXS. The DLS method reveals that electrostatic immobilization of doxorubicin hydrochloride is accompanied by the assembly of 80–90 nm aggregates, wherein the full drug release from nanoparticles occurs in accordance with the first-order kinetic equation. The synthesized nanoparticles were shown to possess paramagnetism and promote significant longitudinal relaxivity (6.77 mM−1 × s−1) of proton spins, making them promising agents for positive MRI imaging. They are also nontoxic to HDF fibroblasts at concentrations up to 0.01 mg × ml−1. Immobilization of doxorubicin hydrochloride slightly reduced its cytotoxicity toward HDF cells and promoted an increase in cytotoxicity for doxorubicin-resistant SiHa cancer cells at drug concentrations up to 0.77 μM. Thus, the developed nanoparticles are promising for the creation of new theranostic agents combining the capabilities of doxorubicin immobilization with MRI diagnostics.