<p>Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer</p>

Abstract

<b>Purpose:</b> Doxorubicin (DOX) encapsulated O-succinyl chitosan graft Pluronic^® F127 (OCP) copolymer nanoparticles conjugated with an anti-HER2 monoclonal antibody were developed as targeted drug delivery vehicles for the treatment of HER2-overexpressing breast cancer. <b>Methods:</b> Five percent and 10% (w/w) of O-succinyl chitosan was grafted onto Pluronic^® F127 using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) as mediated cross-linking agents. DOX was added to the copolymer solution to form DOX-nanoparticles before conjugation with anti-HER2 on the surface of the nanoparticles. <b>Results:</b> DOX was encapsulated within the NP matrices at an encapsulation efficiency of 73.69 ± 0.53% to 74.65 ± 0.44% (the initial DOX concentration was 5 µg/mL). Anti-HER2 was successfully conjugated onto the surface of the nanoparticles at a moderately high conjugation efficiency of approximately 57.23 ± 0.38% to 61.20 ± 4.42%. In the in vitro DOX dissolution study, the nanoparticle formulations exhibited a biphasic drug release with an initial burst release followed by a sustained release profile at both pH 5.0 and pH 7.4. The drug was rapidly and completely released from the nanoparticles at pH 5.0. In the in vitro cytotoxicity, the anti-HER2 conjugated OCP copolymer nanoparticles showed the lowest IC₅₀, which indicated an increase in the therapeutic efficacy of DOX to treat human breast cancer cells with the HER2 overexpression. <b>Conclusion:</b> Our study shows that anti-HER2 conjugated OCP copolymer nanoparticles have the potential for the development of anticancer drug carriers.