Ligand-targeted Theranostic Liposomes combining methylene blue attached upconversion nanoparticles for NIR activated bioimaging and photodynamic therapy against HER-2 positive breast cancer

Methylene Blue (MB) based Photodynamic therapy (PDT) has gained much interest recently due to its FDA approval for treating various diseased conditions in human. Herein, we report for the first time the systematic evaluation of NIR-controlled PDT efficiency of free MB and MB attached on NaYF₄:Yb, Er nanoparticles (UCNPs) i.e., MB@UCNPs encapsulated within Liposomes (LPs). The UCNPs act as an upconverting energy source for the photosensitizers dye MB for enhanced ROS generation and utilizing the remnant energy for selective tracking or bioimaging. The specificity of our nano LPs system was achieved by conjugating our newly discovered anti-HER2 peptides by phage display technique and demonstrated its specificity by confocal imaging of HER-2 overexpressing in vitro model. A significant decline in the cell viability by 83% and 64% was achieved by the LPs containing MB@UCNPs and free MB with UCNPs, respectively after 975 nm NIR laser exposure (0.60 W/cm⁻²) for 5 min continuous exposure. Also, the flowcytometry assay confirmed that enhanced ROS generation capability of LPs with MB@UCNPs was higher than the free MB with UCNPs, which states the relevance of the minimal distance between MB and UCNPs for higher anti-cancer efficiency.