Synthesis of a novel, sequentially active-targeted drug delivery nanoplatform for breast cancer therapy

摘要: Breast cancer is the leading cause of deaths among women. Paclitaxel (PTX), an important breast medicine, exhibits reduced bioavailability and therapeutic index due to high hydrophobicity indiscriminate cytotoxicity. PTX encapsulation in one-level active targeting overcomes such barriers, but enhances toxicity normal tissues with cancer-similar expression profiles. This research attempted overcome this challenge by increasing selectivity cell while maintaining ability traditional pharmacological barriers. Thus, a multi-core, multi-targeting construct for tumor specific delivery was fabricated (i) inner-core prodrug cancer-overexpressed cathepsin B through B-cleavable tetrapeptide that conjugates poly(amidoamine) dendrimer, (ii) (PGD) outer core RES-evading, folate receptor (FR)-targeting liposome. Compared FR-targeting liposomes, sequentially active-targeted dendrosome demonstrated better retention, increased cytotoxicity cells (latter being true when FR activities were both at moderate-to-high levels) higher reduction. may eventually evolve product platform systemic inherent chemotherapy localized single-target nanoplatforms, thereby allowing tolerance load advanced disease states.