An immunoconjugated up-conversion nanocomplex for selective imaging and photodynamic therapy against HER2-positive breast cancer

• Published in: Nanoscale Vol. 1; no. 21; pp. 1154 - 1165
• Main Authors: Ramírez-García, Gonzalo, Panikar, Sandeep S, López-Luke, Tzarara, Piazza, Valeria, Honorato-Colin, Miguel Angel, Camacho-Villegas, Tanya, Hernández-Gutiérrez, Rodolfo, De la Rosa, Elder
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 31.05.2018
• Subjects: Breast cancer; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Cancer; Cell Line, Tumor; Erbium; Humans; Immunoconjugates - pharmacology; Indoles; Infrared radiation; Medical imaging; Molecular chains; Monoclonal antibodies; Nanoconjugates; Organometallic Compounds; Penetration depth; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents; Receptor, ErbB-2 - genetics; Singlet oxygen; Targeted cancer therapy; Theranostic Nanomedicine; Trastuzumab - pharmacology; Upconversion; Ytterbium
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c8nr01512k

Photodynamic therapy represents a very attractive therapeutic tool considered to be effective, minimally invasive and minimally toxic. However, conventional photodynamic therapy actually has two main constraints: the limited penetration depth of visible light needed for its activation, and the lack of selectivity. Considering this, this work reports the synthesis and evaluation of a novel nanoconjugate for imaging and selective photodynamic therapy against HER2-positive breast cancer, a particularly aggressive form of the disease. It was demonstrated that upon 975 nm near infrared light exposure, the red emission of the NaYF 4 :Yb,Er up-conversion nanoparticles (UCNPs) can be used for optical imaging and simultaneously represent the source for the excitation of a covalently bound zinc tetracarboxyphenoxy phthalocyanine (ZnPc), a photosensitizer that in turn transfers energy to ground state molecular oxygen to produce cytotoxic singlet oxygen. The specificity of our nanoconjugates was achieved by immunoconjugation with Trastuzumab (Tras), a specific monoclonal antibody for selective detection and treatment of HER2-overexpressing malignant breast cancer cells. Selective tracking of SKBR-3 HER2-positive cells was verified by confocal microscopy analysis, and the photodynamic therapy effect was considerably improved when Trastuzumab was incorporated into the nanoconjugate, the UCNPs-ZnPc-Tras being practically inert in the absence of infrared light exposure but reducing the HER2-positive cell viability up to 21% upon 5 min of the irradiation. This theranostic nanoconjugate represents a valuable alternative for HER2-positive breast cancer imaging and selective photodynamic therapy. The UCNPs-ZnPc-Trastuzumab nanocomplex tracks and kills HER2-positive breast cancer cells upon NIR-excitation.