Tumor Microenvironment‐Activated NIR‐II Nanotheranostic System for Precise Diagnosis and Treatment of Peritoneal Metastasis

Abstract

Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side‐effects. Herein, a tumor microenvironment (TME)‐activated NIR‐II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self‐assembling the peptide Fmoc‐His, mercaptopropionic‐functionalized Ag2S quantum dots (MPA‐Ag2S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR‐II fluorescence “off” state, because of Ag2S QDs‐A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc‐His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag2S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME‐activated theranostic strategy holds great promise for future clinical applications.

Activatable fluorescence sensors forin vivobio-detection in the second near-infrared window

“…Meanwhile, the released DOX provided chemotherapy effects for this nanotheranostic system. 70 Except for FRET, photoinduced electron transfer (PET) could also be used for uorescence quenching. [71][72][73][74][75] Kim and co-workers selected methylene blue as the PET quencher to suppress the uorescence of PbS/CdS/ZnS QDs through a protease-cleavable peptide sequence.…”

“…Under coordination and electrostatic interaction between Fmoc-His, Er 3+ , Ag 2 S, A1094 and chemodrug doxorubicin (DOX), the five components spontaneously self-assembled into the activatable sensor Fmoc-His/Er 3+ /Ag 2 S/DOX/A1094 (FEAD1) with a quenching efficiency of 82%. 70 Triggered by the acidic tumor micro-environment (pH 5.5), disassembly occurred and the FRET process between Ag 2 S and A1094 was cut off, resulting in the fluorescence recovery of Ag 2 S around 1200 nm. Metastatic nodules in a tumor-bearing mouse model could be precisely profiled and excised under the guidance of “on” state NIR-II imaging with an SBR of 7.0.…”

Near‐Infrared Fluorophores for Thrombosis Diagnosis and Therapy

“…Tumor microenvironment‐activated NIR‐II imaging and a responsive DOX‐releasing strategy opened an innovative method to tumor theranostics. [ 19 ] The biomedical applications of these inorganic fluorescent materials have gained immense interest. However, the i) biosafety concern and potential toxicity caused by long‐term retention in the reticuloendothelial system; and ii) slow metabolism restrict the clinical translation of these inorganic materials.…”

Au‐Doped Ag2Te Quantum Dots with Bright NIR‐IIb Fluorescence for In Situ Monitoring of Angiogenesis and Arteriogenesis in a Hindlimb Ischemic Model

“…[ 7–10 ] Up to now, several NIR‐II fluorescent probes have been developed and deployed for blood hemodynamics visualization, cerebrovascular imaging, and tumor targeting. [ 11–15 ]…”