EGFR-Targeted and NIR-Triggered Lipid-Polymer Hybrid Nanoparticles for Chemo-Photothermal Colorectal Tumor Therapy

Fang Fang,1,* Yun Yan Chen,1,* Xin-Ming Zhang,2 Jin Tang,1 Yu-Hao Liu,1 Chen-Shuo Peng,1 Yu Sun1,3 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2School of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241002, People’s Republic of China; 3Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932026, Email [email protected]: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy. Keywords: Chemo-photothermal therapy, Targeted cancer therapy, Nanoparticles, Cetuximab, Indocyanine green