15P Designing of multimodal targeted tumor-seeking nanomedicine for triple-therapeutic effect

Abstract

Breast cancer is a major ongoing health problem among women in both developing and developed countries. Her2/neu positive is the subtype of breast cancer. We tested an integrated innovatively designed new tumour-seeking nanomedicine (TSN) for high therapeutics antitumor effect on advanced breast cancer that overexpressed the Her2/neu receptor. Herein, we designed the special photodynamic molecule porphyrin combined with the anticancer drug doxorubicin (DOX), enabling it to target cancer biomarkers and measuring the singlet oxygen production with thermal heat to archive extraordinary selective PDT/PTT/Chemotherapy in vitro. The tumor-seeking nanomedicine (TSN) targets the triple therapeutic effect of breast cancer. Furthermore, in vivo phototherapy and chemotherapy using targeted nanoparticles in mice models were also done. Encouragingly, multimodal targeted TSN shows selective Her2/neu receptor-mediated response in breast cancer, incinerates the tumor treated under NIR irradiation triggering the porphyrin and DOX co-release and enhancing the distribution of DOX in nuclei; the released porphyrin molecules also function as multiphase that can efficiently convert NIR-light to heat inside tumor cells for PTT, and again NIR-light to singlet oxygen for PDT. Due to these unique properties, TSN had excellent antitumor effects under NIR irradiation. The excellent role of TSN based triple-targeted therapy produced the best anticancer response to trigger the tumor cell death and was effective to protect the mice from cancer relapse. Conjugation of porphyrin and DOX for the evaluation of such complexes in phototherapy in Her2/neu target human cancer cells. This multi-model therapy approach will make it much more effective to overcome tumors than a single therapeutic approach. TSN exhibited high selectivity and efficient tumor inhibition in-vivo without affecting the normal tissues. Therefore the clinical translation of our TSN and the proposed way might be realistic and the integrated components of TSN have been approved by the US FDA for human clinical usage. Therefore, integrated TSN achieved unprecedented selectivity and shows highly versatile next-generation clinical translation for advanced nanomedicine against cancers.