Development of a cancer cell membrane-coated biomimetic nanoparticle delivery system for the targeted treatment of triple negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking oestrogen, progesterone, and HER2 receptors, limiting targeted treatment options. Conventional chemotherapy is often associated with systemic toxicity and poor tumour specificity. Biomimetic nanomedicine, particularly cancer cell membrane-coated nanoparticles, has emerged as a promising strategy to improve tumour targeting through immune evasion and homotypic recognition.

This study aimed to develop and optimise a cancer cell membrane–coated nanoparticle system for targeted TNBC therapy. Human TNBC (MDA-MB-231) cell membranes were isolated using a reproducible protocol involving hypotonic lysis, sonication, and ultracentrifugation, yielding intact membrane vesicles suitable for nanoparticle coating.

Initial coating feasibility was assessed using curcumin-loaded Pluronic® F127 micelles. Although membrane association was achieved, significant reductions in drug loading were observed due to the instability of micellar systems. To address this limitation, a rigid-core nanocarrier platform using paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles was developed.

Optimisation of coating conditions identified probe sonication at a 1:1 nanoparticle-to-membrane ratio as the most effective method, producing stable nanoparticles with preserved membrane proteins. Functional studies demonstrated significantly enhanced cytotoxicity in MDA-MB-231 cells compared with free paclitaxel and uncoated nanoparticles, with faster cellular uptake and improved disruption of 3D tumour spheroids.

Overall, the developed biomimetic CM–PLGA–PTX nanoparticles demonstrated improved targeting capability, and therapeutic efficacy, highlighting their potential as a targeted nanomedicine strategy for TNBC treatment.