Multifunctional MnO₂ nanoparticles for tumor microenvironment modulation and cancer therapy

Abstract

Tumor microenvironment (TME) is generally featured by low pH values, high glutathione (GSH) concentrations, overproduced hydrogen peroxide (H2O2), and severe hypoxia. These characteristics could provide an interior environment for origination and residence of tumor cells and would lead to tumor progression, metastasis, and drug resistance. Therefore, the development of TME‐responsive smart nanosystems has shown significant potential to enhance the efficacy of current cancer treatments. Manganese dioxide (MnO2)‐based nanosystems have attracted growing attentions for applications in cancer treatment as an excellent TME‐responsive theranostic platform, due to their tunable structures/morphologies, pH responsive degradation, and excellent catalytic activities. In this review, we mainly summarize the strategies of MnO2 and its nanocomposites to modulate TME, such as tumor hypoxia relief, excessive GSH depletion, glucose consumption, and tumor immunosuppressive microenvironment moderation. Such MnO2‐based TME modulation would be beneficial for a wide range of cancer therapies including photodynamic therapy, radiotherapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and immunotherapy. Next, some representative designs of MnO2‐based nanoplatforms in other tumor therapies are highlighted. Moreover, we will discuss the challenges and future perspectives of these MnO2‐based nanosystems for enhanced tumor treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

“…The acidic TME is an important feature of cancer [ 32 , 33 ]. Previous studies indicated that MnO 2 response to acidic TME leading to release of Mn 2+ according to chemical equation: MnO 2 + 2H + → Mn 2+ + H 2 O + 1/2O 2 ↑ [ 34 ]. In order to evaluate the acid sensitivity of GSMM, it was incubated in pH 6.5 buffer solution.…”

Recent Advances in Transition-Metal Based Nanomaterials for Noninvasive Oncology Thermal Ablation and Imaging Diagnosis

“…In terms of composition, TMOs can serve as oxidants because they contain oxygen. This allows TMOs to be reduced and decomposed into transition metal ions in an acidic, hypoxic tumor microenvironment with high levels of glutathione ( Yang G. et al, 2021 ). Therefore, transition metal ions can be used for biological imaging, such as Mn ions-mediated magnetic resonance imaging (MRI) ( Zheng et al, 2021 ).…”

Manganese-based hollow nanoplatforms for MR imaging-guided cancer therapies

“…Over the past 10 years, Mn-based nanomaterials such as Mn x O y and MnS have drawn increasing interest in biomedical applications [ 28 – 32 ]. These nanoplatforms with passive or active targeting ability are capable of selectively accumulating at the tumor site, which leads to highly effective MR imaging after degradation in the tumor microenvironment (TME) [ 33 , 34 ]. In addition, Mn is one of the necessary elements in human bodies for metabolism, and its uptake and excretion can be efficiently controlled by biological systems, resulting in low toxicity and high biosafety [ 35 – 37 ].…”

“…Among the hollow TME-responsive DDSs, Mn-based nanoplatforms display tremendous promise in bioimaging, drug delivery and tumor therapy owing to their good biocompatibility, unique hollow structures and excellent physical/chemical performances [ 69 , 82 ]. For instance, hollow MnO 2 nanoparticles can rapidly respond to the TME, catalyzing intracellular hydrogen peroxide (H 2 O 2 ) to produce O 2 and concurrently depleting the overexpressed glutathione (GSH) [ 33 , 83 ]. The generated O 2 benefits additional treatment modalities, such as chemotherapy [ 84 ], RT [ 85 ], photodynamic therapy (PDT) [ 84 ], sonodynamic therapy (SDT) [ 86 ] and starvation therapy (ST) [ 87 ], while the consumption of GSH leads to redox imbalance and further improves the curative effects of reactive oxygen species (ROS)-mediated therapies [ 88 ].…”