Does an Adriamycin and Olaparib co-loaded dual responsive nanoparticle improve therapeutic efficacy and reduce toxicity in triple negative breast cancer models compared to free drugs?
A novel pH and GSH dual-responsive nanoparticle co-delivering Adriamycin and Olaparib demonstrates enhanced anti-tumor efficacy and reduced systemic toxicity in preclinical models of triple-negative breast cancer.
A pH and GSH concentration dual responsive material was designed to address the insufficient efficacy and toxicity in triple negative breast cancer (TNBC) clinical chemotherapy. Methyl polyethylene glycol (mPEG) and oligomeric HA (o-HA) were conjugated to PLGA via hydrazone and disulfide bonds, respectively. The Adriamycin (ADR) and Olaparib (Ola) co-loaded dual responsive nano drug delivery system was prepared by double-emulsion method. The particle size was 173.78 ± 15.1 nm with a zeta potential of −9.88 ± 0.33 mV. Transmission electron microscopy revealed spherical nanoparticle (NP) with a bilayered structure. The encapsulation efficiencies for Adriamycin and Olaparib were 99.99 % and 73.91 %, respectively. The Drug loading was 4.76 % and 3.56 % accordingly. The particle size, potential and drug release profile demonstrated pH and GSH concentration sensitivity. The blank NP inhibited TNBC cells migration and invasion while showed good compatibility with L929 cell. The co-loaded NP showed exhibited synergistic cytotoxicity on TNBC cells and promoted apoptosis. The NP exhibited tumor targeting properties both in vitro and in vivo. Co-loaded NP showed significant stronger therapeutic effects in mice TNBC orthotopic tumor and lung metastasis models than the free drugs and the single-loaded NP with lower systemic toxicity.
Li et al. (2025) studied this question.