RESUMO
In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.
Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Lignina , Nanopartículas , Estresse Oxidativo , Polietilenoglicóis , Espécies Reativas de Oxigênio , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Lignina/química , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Feminino , Humanos , Portadores de Fármacos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/química , Anidridos Maleicos/químicaRESUMO
Shape memory polymers (SMPs) responsive to various external stimuli can realize a complex shape transformation process and have attracted extensive attention. However, integrating multiple stimulus-responsive mechanisms in one material often requires a complex molecular design and synthesis procedure. In this work, we designed a novel dual-responsive heterogeneous hydrogel (PU-PAM/Alg/PDA), which was manufactured through in situ free radical polymerization of acrylamide (AM) in the presence of alginate (Alg) and polydopamine (PDA) in a porous polycaprolactone-based polyurethane foam (PU-foam). The PU-PAM/Alg/PDA hydrogel could achieve thermal responsiveness through melting-crystallization transformation of polycaprolactone (PCL), while the metallo-supramolecular interactions between Alg and Fe3+ could provide ion responsiveness for this hydrogel. This dual-programmable feature endowed the heterogeneous hydrogel with a complex shape-morphing behavior and also a reconfiguration ability for the permanent shape. Meanwhile, the strong hydrogen bondings between PDA and polyurethane chains enhanced the interfacial adhesions, resulting in the structural integrity and excellent mechanical property of PU-PAM/Alg/PDA. The in vitro and in vivo tests revealed the good biocompatibility of the heterogeneous hydrogel, and the potential of the heterogeneous hydrogel as an esophageal stent was evaluated in vitro as conceptual proof.