Tumor‐Microenvironment‐Triggered Ion Exchange of a Metal–Organic Framework Hybrid for Multimodal Imaging and Synergistic Therapy of Tumors

Abstract

Nanotheranostic agents (NTAs) that integrate diagnostic capabilities and therapeutic functions have great potential for personalized medicine, yet poor tumor specificity severely restricts further clinical applications of NTAs. Here, a pro‐NTA (precursor of nanotheranostic agent) activation strategy is reported for in situ NTA synthesis at tumor tissues to enhance the specificity of tumor therapy. This pro‐NTA, also called PBAM, is composed of an MIL‐100 (Fe)‐coated Prussian blue (PB) analogue (K2Mn[Fe(CN)6]) with negligible absorption in the near‐infrared region and spatial confinement of Mn2+ ions. In a mildly acidic tumor microenvironment (TME), PBAM can be specifically activated to synthesize the photothermal agent PB nanoparticles, with release of free Mn2+ ions due to the internal fast ion exchange, resulting in the “ON” state of both T1‐weighted magnetic resonance imaging and photoacoustic signals. In addition, the combined Mn2+‐mediated chemodynamic therapy in the TME and PB‐mediated photothermal therapy guarantee a more efficient therapeutic performance compared to monotherapy. In vivo data further show that the pro‐NTA activation strategy could selectively brighten solid tumors and detect invisible lymph node metastases with high specificity.

Chemodynamic nanomaterials for cancer theranostics

“…Prussian blue-based nanomaterials have shown promise for both PTT and Fenton-reaction mediated CDT [ 186 ]. In one study, MIL-100 (Fe) coated K 2 Mn[Fe(CN) 6 ] NPs (PBAM) were prepared for CDT and PTT combination therapy [ 187 ]. In the mildly acidic TME, the MIL-100 shell was degraded to release Fe 3+ , which further exchanged with Mn 2+ to synthesize Prussian blue for PTT.…”

Biodegradable Metal Organic Frameworks for Multimodal Imaging and Targeting Theranostics

“…This MOF realized tumor targeted multimodal imaging (Near-infrared fluorescence images, PAI, and MRI). [20]. In the mildly acidic tumor microenvironment, the MIL-100 shell was degraded, and the released Fe 3+ exchanged with Mn 2+ to synthesize in situ the more stable PB, Fe 3+ -[Fe(CN)6] 4− , and to release free Mn 2+ .…”

“…The excellent PAI and PTT of PB, and T1-weighted MRI and CDT of Mn 2+ showed accurate theranostic effects (Figure 10). [20]. In the mildly acidic tumor microenvironment, the MIL-100 shell was degraded, and the released Fe 3+ exchanged with Mn 2+ to synthesize in situ the more stable PB, Fe 3+ -[Fe(CN)6] 4− , and to release free Mn 2+ .…”

Manganese-doped gold nanoclusters with ultrasmall size andmicroenvironment-responsive visualized theranostics of tumor

“…纳米酶在肿瘤微环境响应的 CDT/PDT 中研究较多 [10][11][12] . 无机纳米材料具有优异的磁、光、电、声和热等响 应特性，可以作为智能响应型纳米酶，在肿瘤可视 化诊疗中显示出潜在的应用前景 [13] .韩国国立首尔大…”