Selective Tumor Hypoxia Targeting Using M75 Antibody Conjugated Photothermally Active MoOx Nanoparticles
Adriana Annušová, Martina Labudová, Daniel Truchan, Veronika Hegedűšová, Helena Švajdlenková, Matej Mičušík, Mário Kotlár, Lenka Pribusová Slušná, Martin Hulman, Farnoush Salehtash, Anna Kálosi, Lucia Csáderová, Eliška Švastová, Peter Šiffalovič, Matej Jergel, Silvia Pastoreková, Eva Majková
Photothermal therapy, PTT, cancer, tumor, MoOx, M75, carbonic anhydrase IX, CAIX
Photothermal therapy (PTT) mediated at the nanoscale has a unique advantage over currently used cancer treatments, by being spatially highly specific and minimally invasive. Although PTT combats traditional tumor treatment approaches, its clinical implementation has not yet been successful. The reasons for its disadvantage include an insufficient treatment efficiency or low tumor accumulation. Here, we present a promising new PTT platform combining a recently emerged two-dimensional (2D) inorganic nanomaterial, MoOx, and a tumor hypoxia targeting element, the monoclonal antibody M75. M75 specifically binds to carbonic anhydrase IX (CAIX), a hypoxia marker associated with many solid tumors with a poor prognosis. The as-prepared nanoconjugates showed highly specific binding to cancer cells expressing CAIX while being able to produce significant photothermal yield after irradiation with near-IR wavelengths. Small aminophosphonic acid linkers were recognized to be more effective over the combination of poly(ethylene glycol) chain and biotin–avidin–biotin bridge in constructing a PTT platform with high tumor-binding efficacy. The in vitro cellular uptake of nanoconjugates was visualized by high-resolution fluorescence microscopy and label-free live cell confocal Raman microscopy. The key to effective cancer treatment may be the synergistic employment of active targeting and noninvasive, tumor-selective therapeutic approaches, such as nanoscale-mediated PTT. The use of active targeting can streamline nanoparticle delivery increasing photothermal yield and therapeutic success.