Multifunctional Mesoporous Hollow Cobalt Sulfide Nanoreactors for Synergistic Chemodynamic/Photodynamic/Photothermal Therapy with Enhanced Efficacy

Abstract

The unique tumor microenvironment (TME) characteristic of severe hypoxia, overexpressed intracellular glutathione (GSH), and elevated hydrogen peroxide (H2O2) concentration limit the anticancer effect by monotherapy. In this report, glucose oxidase (GOx)-encapsulated mesoporous hollow Co9S8 nanoreactors are constructed with the coverage of polyphenol diblock polymers containing poly(oligo(ethylene glycol) methacrylate) and dopamine moieties containing methacrylate polymeric block, which are termed as GOx@PCoS. After intravenous injection, tumor accumulation, and cellular uptake, GOx@PCoS deplete GSH by Co3+ ions. GOx inside the nanoreactors produce H2O2 via oxidation of glucose to enhance •OH-based chemodynamic therapy (CDT) through the Fenton-like reaction under the catalysis of Co2+. Moreover, Co3+ ions possess catalase activity to catalyze production of O2 from H2O2 to relieve tumor hypoxia. Upon 808 nm laser irradiation, GOx@PCoS exhibit photothermal and photodynamic effects with a high photothermal conversion efficiency (45.06%) and generation capacity of the toxic superoxide anion (•O2 –) for photothermal therapy (PTT) and photodynamic therapy (PDT). The synergetic antitumor effects can be realized by GSH depletion, starvation, and combined CDT, PTT, and PDT with enhanced efficacy. Notably, GOx@PCoS can also be used as a magnetic resonance imaging (MRI) contrast agent to monitor the antitumor performance. Thus, GOx@PCoS show great potentials to effectively modulate TME and perform synergistic multimodal therapy.

CoFeSe2@DMSA@FA Nanocatalyst for Amplification of Oxidative Stress to Achieve Multimodal Tumor Therapy**

“…In addition, Cobased nanomaterials have been reported to exhibit excellent peroxidase-like activity, enabling them to catalyze the generation of O 2 from hydrogen peroxide. [41][42][43] As expected, the CFSDF nanocatalyst rapidly produced abundant O 2 in the hydrogen peroxide solution, while the solution containing only CFSDF nanocatalyst or hydrogen peroxide did not generate O 2 (Figure S9).…”

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

“…In view of Cobalt (Co) possesses higher peroxidase-like and catalase-like activities than that of Fe, Chen and co-workers fabricated a nanoenzymes-engineered MOF (Apatinib@ZIF67@polydopamine, AZP NCs nanoenzymes) by encapsulating antiangiogenic agent of Apatinib (AP) in situ into the pores of Co-ZIF that alleviated tumor hypoxia by converting intratumoral H 2 O 2 to O 2 through Co­(II) with peroxidase-like activities This process enhances the generation of ROS, which improves the effectiveness of MDT therapy . Li et al constructed a GOx-encapsulated mesoporous hollow Co 9 S 8 nanoreactors (GOx@PCoS) that can produce H 2 O 2 via oxidation of glucose to enhance center dot OH-based CDT through the Fenton-like reaction under the catalysis of Co 2+ . The Co 3+ ions possess catalase activity to catalyze the generation of O 2 from H 2 O 2 to relieve tumor hypoxia.…”

“…222 Li et al constructed a GOx-encapsulated mesoporous hollow Co 9 S 8 nanoreactors (GOx@PCoS) that can produce H 2 O 2 via oxidation of glucose to enhance center dot OH-based CDT through the Fenton-like reaction under the catalysis of Co 2+ . 223 The Co 3+ ions possess catalase activity to catalyze the generation of O 2 from H 2 O 2 to relieve tumor hypoxia. The synergetic antitumor effects of GOx@PCoS can be achieved by depleting GSH by Co 3+ ions, starvation, and combined PTT, CDT, and PDT.…”

Cascade strategy for glucose oxidase-based synergistic cancer therapy using nanomaterials

“…Thus, with the assistance of replenished O 2 , the versatile nanosystem demonstrated a potent cytotoxic effect against cancer cells. Being inspired, Li et al 137 recently designed a multifunctional mesoporous hollow Co 9 S 8 nanoreactor loaded with GOx for multimodal combination therapy. Similar to the Cu + -catalyzed Fenton-like reaction, multivalent Co 2+ /Co 3+ engaged in GSH depletion to generate ˙OH, synergistically mediating GOx-enhanced CDT.…”