Intravital Whole‐Process Monitoring Thermo‐Chemotherapy Via 2D Silicon Nanoplatform: A Macro Guidance and Long‐Term Microscopic Precise Imaging Strategy

Abstract

Tumor angiogenesis is a complex process that is unamenable to intravital whole‐process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging‐optical coherence tomography angiography (OCTA)‐laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo‐chemotherapy of tumor by monitoring blood oxygen saturation (SaO2) and hemoglobin content (HbT), but also capable of long‐term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo‐chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5‐fluorouracil silicon nanosheets (5‐Fu‐Si NSs) therapeutic agent is designed. Furthermore, 2D high‐resolution tumor microvascular images in different stage display that tendency of the thermo‐chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale.

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy

“…A back skin window from HeLa tumor BALB/c nude mice was constructed in accordance with our previous report. 8 4.4. Fabrication of Nanotheranostics.…”

“…Although several commonly employed molecular imaging strategies, such as micro-CT (μCT), micro-MR (μMR), and fluorescence microscopy imaging, have been employed to explore angiogenesis of tumors in clinical or preclinical models, μCT and μMR cannot exhibit a single vessel on account of their limited spatial resolution. 8 Fluorescence microscopy demands exogenous contrast agents to label vasculature, hindering continuous imaging research in vivo. 61 In light of the abovementioned concerns, the burgeoning microscopic ultra-high-resolution LS imaging was utilized to monitor changes of microvascular hemodynamics during therapy.…”

“…4,5 Recently, antiangiogenic efficacy is mainly evaluated by the expression level of new VEGF in vitro. 6,7 In view of the fact that the microscopic precise imaging [e.g., optical coherence tomography angiography (OCTA)/laser speckle (LS) imaging] monitor method has attracted increasing attention for noninvasively feeding back the tumor-microvascular progression, evaluating antiangiogenic therapeutic efficacy and quantifying microvascular functional parameters before and after therapy, 8,9 we were greatly motivated and interested in OCTA/LS imaging, which not only enables to precisely guide the oncotherapy but also can monitor both microvascular morphology and hemodynamic changes during tumor growth and after tumor treatment in vivo. Fortunately, our preliminary experiments have substantially confirmed that OCTA/LS imaging can precisely monitor the microvascular morphology during antiangiogenic therapy.…”

Research progress on the application of optical coherence tomography in the field of oncology

“…OCT technology offer changes in tumor microvascular before and after treatment to assess tumor microvascular response to nano therapy. This creates the theoretical and technical base for developing new tumor-specific diagnostic and treatment approaches ( 50 ). Welzel et al.…”

“… (A) Schematic of subcutaneous tumor-bearing nude mice dorsal window imaging; (B) Subcutaneous tumors of nude mice with tumors enlarge the skin window chamber images; (C) The zoom-in skin window chamber image in the healthy nude mice; (D) The corresponding enface microvascular image in vivo is shown in (C) ; (E) Representative tissue cross sectional structural image (gray) and blood flow image (red border); (F) The zoom-in skin window chamber image in the subcutaneous tumor-bearing nude mice; (G) The corresponding enface microvascular image in vivo is shown in (F) ( 50 ); Copyright 2021, Wiley. (H) Normal vascular OCT images; (I) OCT images of angiogram and lymphangiography.…”