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

Abstract

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 NaYF4: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.

Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

“…An additional avenue of HER2-positive cancer imaging is the use of nanoconjugates, which involves linking bioconjugates to nanoparticles (NPs) for delivery into cancer cells. A previous study has demonstrated the specific detection of only HER2-positive cells in vitro using the HER2-positive SKBR3 human breast cancer cell line [120]. This opens avenues for further research into PDD of HER2-positive tumors.…”

Inorganic Nanoparticles Applied for Active Targeted Photodynamic Therapy of Breast Cancer

“…After 28 days of a double PDT application, mice injected with MNPs(MC540)/DSPE-PEG-NPY showed no tumor growth [151]. In a study performed by Ramírez-García et al (2018), a UCNP nanoconjugate was constructed for the targeted PDT and imaging against HER-2-positive BC cells, as well as to try and overcome the limited tumor cell depth penetration visible light has [152]. NaYF4:Yb,Er UCNPs were fabricated and attached to a zinc tetracarboxyphenoxy phthalocyanine (ZnPc) PS and a trastuzumab (Tras) HER-2 specific monoclonal antibody to form a UCNPs-ZnPc-Tras nanocomposite [152].…”

“…In a study performed by Ramírez-García et al (2018), a UCNP nanoconjugate was constructed for the targeted PDT and imaging against HER-2-positive BC cells, as well as to try and overcome the limited tumor cell depth penetration visible light has [152]. NaYF4:Yb,Er UCNPs were fabricated and attached to a zinc tetracarboxyphenoxy phthalocyanine (ZnPc) PS and a trastuzumab (Tras) HER-2 specific monoclonal antibody to form a UCNPs-ZnPc-Tras nanocomposite [152]. The covalent bonds between UCNPs and ZnPc resulted in resonance energy transfer from the NPs to the PS, which in turn produced cytotoxic singlet oxygen and higher 1 O2 quantum yields when compared to control groups [152].…”

Algunas aplicaciones de la nanofotónica en la biomedicina

“…Más aún, es posible utilizar nanocomplejos de diferentes colores permitiendo desarrollar sistemas multiplexados capaces de detectar más de un complejo de interés. Con esta técnica, recientemente se ha reportado la detección de Vaspin, una proteína presente en la sangre que puede causar diabetes tipo 2, en concentraciones tan bajas como 35 pg/ml (Ali et al, 2017) Fuente: Información detallada para la síntesis de este tipo de NPs puede encontrarse en: G. Ramírez-García et al (2018.…”

“…En el ámbito terapéutico, los nanomateriales han sido ampliamente utilizados en terapia fotodinámica, terapia fototérmica y como acarreadores de fármacos o nanovectores (Huang et al, 2006;Gobin et al, 2007;Ramírez-García et al, 2018;Zhou et al, 2017). Más recientemente se han venido desarrollando complejos teranósticos que combinan detección, imagen y terapia permitiendo también monitorear el efecto de la misma Lammers et al, 2011;Bai et al, 2015;Gobin et al, 2007;Ramírez-García et al, 2018;Zhou 13(24), 1e-24e, enero-junio 2020 | http: //dx.doi.org/10.22201/ceiich.24485691e.2020.24.69618 Elder De la Rosa, Gonzalo Ramírez, Sandeep Panikar, Tanya Camacho, Pedro Salas, Tzarara López-Luke et al, 2017. Estos complejos prometen la implementación de una medicina personalizada y preventiva aprovechando la alta sensibilidad de las técnicas de detección ya discutidas.…”