NIR-IIb fluorescence-image guided synergistic surgery/starvation/chemodynamic therapy: an innovative treatment paradigm for malignant non-small cell lung cancers

Abstract

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce 3+ doped in the core and 100% Yb 3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce 3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H2O2 to boost the CDT mediated by the Mn 2+ and Cu 2+ , which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion:This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection

“…In modern thoracoscopic surgery, reduced tactile feedback may lead to inaccurate nodule localization due to smaller incisions. , New intraoperative imaging techniques are essential to locate lung nodules and ensure R0 resections are performed accurately. With its strong penetration and excellent imaging capabilities, NIR-II fluorescence has demonstrated the specific identification ability for intrapulmonary tumors in previous studies. ,, …”

“…With its strong penetration and excellent imaging capabilities, NIR-II fluorescence has demonstrated the specific identification ability for intrapulmonary tumors in previous studies. 6,15,16 The combination of MRI and NIR-II imaging is used to meet the current clinical diagnostic and therapeutic needs. For patients with advanced-stage lung cancer, neoadjuvant therapy has gradually become the standard treatment.…”

Manganese(III) Phthalocyanine Complex Nanoparticle-Loaded Glucose Oxidase to Enhance Tumor Inhibition through Energy Metabolism and Macrophage Polarization

“…This reaction was employed by loading GOx to construct a multifunctional nanoplatform, not only for tumor starvation therapy but also to benefit CDT . A popular approach combines these two factors to construct a nanoplatform as CDT agents, further augmenting the effectiveness of CDT. , For example, Yang and co-workers loaded ultrasmall γ-Fe 2 O 3 nanoparticles and glucose oxidase (GOx) into dendritic mesoporous silica (DMSN) spheres, synthesizing magnetic targeting nanoplatform (γ-Fe 2 O 3 –GOx–DMSN) . In acidic TME, the γ-Fe 2 O 3 nanoparticles could generate • OH from H 2 O 2 , which was produced as a side product of glucose consumption by GOx, through the Fenton reaction.…”

Optimized core–shell lanthanide nanoparticles with ultrabright Ce3+-modulated second near-infrared emission for “lighting” plants

“…29–31 The NIR-II DC luminescence falls into the optical transmission window of biological tissues, providing deep tissue penetration and thus improving the temporal and spatial resolution of imaging. 32–34 That is to say, LDNPs with bright NIR-II emission can serve as the ideal fluorescent nanoprobes for optical bioimaging. 35–38…”