Abstract
Controlling delivery and release of therapeutic agents to accomplish on-demand synergistic therapy of orthotopic gliomas is desired but challenging. Here, we report a glioma targeting and redox activatable theranostic nanoprobe (Co-NP-RGD1/1) for magnetic resonance (MR) and fluorescence (FL) bimodal imaging-guided on-demand synergistic chemotherapy/photodynamic therapy (Chemo-PDT) of orthotopic gliomas. Co-NP-RGD1/1 is formed via molecular coassembly of two paramagnetic and fluorogenic small-molecule probes CPT-RGD and PPa-RGD at an optimized molar ratio of 1/1, which shows a high longitudinal relaxivity (r1 = 17.0 ± 0.6 mM-1 s-1, 0.5 T) but weak FL emissions and low Chemo-PDT activity. Upon reduction by endogenous glutathione (GSH), Co-NP-RGD1/1 disassemble and release small molecules 2-RGD, chemodrug camptothecin (CPT), and near-infrared (NIR) photosensitizer (PS) PPa-SH that further binds to endogenous albumin to form PPa-SH-albumin complex, allowing to turn on FL, chemotherapeutic efficacy, and PDT activity for synergistic Chemo-PDT of orthotopic U87MG or U251 gliomas in living mice. Moreover, Co-NP-RGD1/1 can also allow noninvasive detection and monitoring of orthotopic brain tumor growth via FL and MR imaging. Findings suggest the potential of cascade coassembly and stimuli-controlled intracellular disassembly strategy for constructing targeted and activatable nanoagents for improving combinational cancer theranostics.
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