Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple-Augmented Chemodynamic Therapy of Cancer.

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.

Metal-Free Organo-Theranostic Nanosystem with High Nitroxide Stability and Loading for Image-Guided Targeted Tumor Therapy.

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r1 = 1.58 mM-1 s-1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.