GSH-Sensitive Nanoscale Mn-Sealed Coordination Particles as Activatable Drug Delivery Systems for Synergistic Photodynamic-Chemo Therapy.

Activatable nanoscale drug delivery systems (NDDSs) are promising in maximizing cancer specificity and anticancer efficacy, and a multifunctional metal-organic nanomaterial is one of the new star NDDSs which requires further exploration. Herein, a novel DOX@MnCPs/PEG NDDSs were constructed by first synthesizing Mn-sealed coordination particles (MnCPs), modified with a targeted PEGylated polymer, and then loading anticancer drug doxorubicin (DOX). MnCPs were prepared from the assembly of Mn ions and hematoporphyrin monomethyl ether (HMME) molecules. Furthermore, MnCPs had an average size of ∼100 nm and a large surface area (∼52.6 m g) and porosity (∼3.6 nm). After the loading of DOX, DOX@MnCPs/PEG exhibited a high DOX-loading efficacy of 27.2%, and they reacted with glutathione (GSH) to confer structural collapse, leading to the production of Mn ions for enhanced magnetic resonance imaging (MRI), free HMME for augmented photodynamic effect, and free DOX for chemotherapy. As a consequence, these DOX@MnCPs/PEG NDDSs after intravenous injection showed efficient tumor homing and then exerted an obvious suppression for tumor growth rate by synergistic photodynamic-chemo therapy . Importantly, most of the DOX@MnCPs/PEG NDDSs could be gradually cleared through the renal pathway, and the remaining part could slowly be metabolized via the feces, enabling high biosafety. Therefore, this work provides a type of GSH-sensitive NDDS with biosafety, caner specificity, and multifunctionality for high synergistic treatment efficacy.