Catalytically Active CoFe₂O₄ Nanoflowers for Augmented Sonodynamic and Chemodynamic Combination Therapy with Elicitation of Robust Immune Response

Abstract

A hypoxic and acidic tumor microenvironment (TME) plays a significant role in cancer development through complex cellular signaling networks, and it is thus challenging to completely eradicate tumors via monotherapy. Here, PEGylated CoFe 2 O 4 nanoflowers (CFP) with multiple enzymatic activities, serving as bioreactors responsive to TME cues, were synthesized via a typical solvothermal method for augmented sonodynamic therapy (SDT) and chemodynamic therapy (CDT) with elicitation of robust immune response. The CFP occupying multivalent elements (Co 2+/3+ , Fe 2+/3+ ) exhibited strong Fenton-like and catalase-like activity. In another aspect, CFP itself is a brand-new sonosensitizer for highperformance SDT based on ultrasound-triggered electron (e − )/ hole (h + ) pair separation from the energy band with promptness and high efficiency. With efficient enrichment in tumorous tissue as revealed by magnetic resonance imaging, CPF could generate • OH for CDT relying on Fenton-like reactions. Moreover, catalase-mimicking CFP could react with endogenous H 2 O 2 to generate molecular oxygen, and high O 2 level may promote the production of 1 O 2 for SDT. What's more, the reactive oxygen species obtained from combined SDT/CDT could efficiently trigger immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade for the sake of suppressing primary and distant tumors as well as lung metastasis. Taken together, this paradigm delivers useful insights for developing in-coming nanocomposites based on cobalt ferrite for cancer theranostics.

Recent advances of cancer chemodynamic therapy based on Fenton/Fenton-like chemistry

“…12b ). 60 Notably, along with the CDT treatment process, an elicitation of robust immune response occurred. And the CFP nanoflower containing multivalent elements (Fe 2+ / 3+ , Co 2+ / 3+ ) show highly Fenton-like and catalytic activity.…”

Stimuli-Responsive Drug Delivery Systems for the Diagnosis and Therapy of Lung Cancer

“…The combinatorial treatment of SDT with other therapeutic strategies, such as chemotherapy and chemodynamic therapy (CDT), has a synergistic effect in the treatment of lung cancer [ 54 ]. For example, Shiyan Fu et al synthesized PEGylated Co 2 Fe 2 O 4 nanoflowers (CFP) [ 55 ]. This CFP occupying multivalent elements (Co 2+/3+ and Fe 2+/3+ ) exhibited strong Fenton-like and catalase-like activity.…”

“…Thermal, mechanical, and chemical effects are not entirely independent and sometimes two or three of them may result in a synergistically therapeutic modality. For instance, Xiaotu Ma et al fabricated a cerasomal perfluorocarbon nanodroplet (D-vPCs-O 2 ) with an atomic layer of polyorganosiloxane and pH-sensitive tumor-targeting peptide [ 55 ]. Oxygen and doxorubicin were co-loaded into the nanodroplets.…”

Nanosonosensitizers With Ultrasound-Induced Reactive Oxygen Species Generation for Cancer Sonodynamic Immunotherapy

“…To overcome the limitations of SDT, the combination of SDT and chemodynamic therapy (CDT) with immune checkpoint therapy can be adopted. As an example, a multifunctional nanoreactor of polyethylene glycol (PEG)-modified CoFe 2 O 4 nanoflowers (CFPs) was synthesized using a typical solvothermal method for an augmented SDT/CDT-elicited robust immune response (Fu et al, 2021). The CFP showed a catalase-like activity to produce a hydroxyl radical (•OH) for CDT and catalyze the decomposition of H 2 O 2 in a tumor microenvironment to form O 2 to relieve tumor hypoxia, which enabled the generation of a high level of 1 O 2 under US irradiation to achieve effective SDT.…”