An Activatable Polymeric Nanoprobe for Fluorescence and Photoacoustic Imaging of Tumor‐Associated Neutrophils in Cancer Immunotherapy

Abstract

Imaging to evaluate tumor‐associated neutrophils (TANs) is imperative for cancer immunotherapy but remains challenging. We herein report an activatable semiconducting polymer nanoprobe (SPCy) for near‐infrared fluorescence (NIRF) and photoacoustic (PA) imaging of neutrophil elastase (NE), a biomarker of TANs. SPCy comprises a semiconducting polymer conjugated with a hemicyanine (hemi‐Cy) dye caged by a NE‐cleavable peptide as the side chain. After systemic administration, SPCy passively targets the tumor and reacts with NE to “uncage” the hemi‐Cy, leading to enhanced NIRF and PA signals of the hemi‐Cy but unchanged signals of the SP. Such NE‐activated ratiometric NIRF and enhanced PA signals of SPCy correlate with the intratumoral population of TANs. Thus, this study not only presents the first TAN‐specific PA probe, but also provides a general molecular design strategy for PA imaging of other immune‐related biomarkers to facilitate screening of cancer immunotherapeutics.

Identification of Immune and Hypoxia Risk Classifier to Estimate Immune Microenvironment and Prognosis in Cervical Cancer

“…Previous studies have uncovered the higher ratios of CD8+ to CD4+ T cells being closely related to improved survival [ 70 ]. On the contrary, the infiltration of neutrophils is proven to be positively correlated with survival of CC patients in our model, which is consistent with the common view that neutrophils are regarded as the most important leukocytes involving in first line defense to tissue damage [ 71 – 73 ]. Compared to the classic discipline to divide tumor immunophenotype into three subtypes (hot, altered, and cold), our finding compared the immune cell infiltration in high- and low-risk populations, may provide a more accurate model to guide the cellular based immunotherapy in CC.…”

3D Multiparametric Photoacoustic Computed Tomography of Primary and Metastatic Tumors in Living Mice

“…The wavelength-dependent light-absorbing characteristics of each biomolecule enable selective imaging by controlling the laser wavelength. Such selective imaging allows PACT to provide high-spatial-resolution and high-contrast information about structures such as vascular anatomy, using only endogenous biomolecules (e.g., hemoglobin, melanin, lipids, and water). − Moreover, by using exogenous contrast agents that take advantage of wavelength-dependent absorption and inherent molecular sensitivity, PACT can provide physiological information and high-contrast molecular imaging. ,− Moreover, PACT can noninvasively obtain SO 2 information without any contrast agents, unlike conventional approaches that rely on an invasive sensor or exogenous contrast agents (e.g., a CT-guided pO 2 sensor, dynamic contrast-enhanced MRI (DCE-MRI), and PET). ,,, In addition, unlike PET and FLI, PACT can provide 3D tomographic image information based on the depth-resolved signal, can enable in vivo molecular-sensitive pharmacokinetics analysis, and can capture the vascular anatomy with a high spatial resolution. ,− Exploiting PACT’s multiparametric imaging capabilities, this modality has been actively employed in preclinical and clinical oncologic research. − …”

Neutral Cyanine: Ultra‐Stable NIR‐II Merocyanines for Highly Efficient Bioimaging and Tumor‐Targeted Phototheranostics

“…[8][9][10][11][12][13] These imaging techniques facilitate precise tumor localization, enabling guided photothermal elimination of tumors. [14,15] However, FLI is constrained by its limited penetration depth and background signal interference when operating within the NIR-I (700-900 nm) fluorescence range. [16,17] On the other hand, PAI provides deeper tissue penetration but lacks resolution and speed of imaging.…”