Trastuzumab-conjugated liposomes for co-delivery of paclitaxel and anti-abcb1 siRNA in HER2-positive breast cancer: In vitro and in vivo evaluations

Chemotherapeutic drugs often face challenges such as non-specific binding, undesired toxicity, and limited blood circulation, leading to reduced therapeutic efficacy. This study introduces HER2-specific targeted nanoparticles designed by synthesizing cationic liposomes. These liposomes encapsulate paclitaxel and ABCB1-siRNA in their core and feature a therapeutic monoclonal antibody, trastuzumab, on the surface. This design aims for precise targeting and synergistic treatment of HER2-positive breast cancer cells in both in vitro and in vivo models. The optimized trastuzumab-conjugated liposomes exhibited a particle size of 229 +/- 4 nm and a zeta potential of 43.46 +/- 0.61 mV. Their spherical morphology was confirmed using Scanning Electron Microscopy (SEM). These liposomes demonstrated enhanced drug retention in in vitro release studies. Furthermore, trastuzumabconjugated liposomes displayed markedly higher cellular uptake than their non-trastuzumab-conjugated counterparts. Their anticancer efficacy in BT -474 cells significantly surpassed that of non -targeted liposomes and unencapsulated paclitaxel. In xenograft Nude mice models derived from the BT -474 cell line, trastuzumabconjugated liposomes showed superior tumor distribution and preclinical effectiveness compared to both nontargeted liposomes and plain paclitaxel.