Novel anti-HER2 Peptide conjugated Theranostic Nanoliposome combining NaYF4:Yb,Er nanoparticles for NIR-activated Bioimaging and Chemo-Photodynamic therapy against Breast Cancer
Herein, we report the fabrication of novel peptide conjugated Ligand targeted nanoliposomes (LTLs) for chemo-photodynamic therapy against HER2-positive breast cancer. The LTL core was utilized for encapsulating doxorubicin (DOX) for chemotherapy, and methylene blue (MB) attached NaYF4:Yb,Er upconversion nanoparticles (UCNPs) for NIR activated bioimaging and leveraging its visible emission for photoexciting MB for enhanced photodynamic therapy (PDT). The specificity of our LTLs was achieved by conjugating a newly discovered anti-HER2 peptide screened from a phage display peptide library. The high selectivity of the peptide conjugated LTLs was confirmed by confocal imaging of SKBR-3 (HER2-positive) and MCF-7 (HER2-negative) breast cancer cell lines, illustrating its target-specific nature. The energy transfer from UCNPs to MB was verified, enabling the generation of reactive oxygen species upon activation with a 975 nm laser source (0.60 W/cm-2) under 5 min continuous excitation. A significant decline in the cell viability by 95% was observed using a chemo-photodynamic combinational therapy, whereas for chemo-drug alone and PDT alone, the cell proliferation was declined by 77% and 84%, respectively. Furthermore, we demonstrated an improved uptake of the LTLs inside a 3D model of SKBR-3 tumor spheroids, where the spheroid cell viability was suppressed by 66% after the use of chemo-photodynamic combinational therapy. Thus, our results suggest great prospective for the use of theranostic LTLs for breast cancer management.