Development of anti-HER2-targeted doxorubicin-core-shell chitosan nanoparticles for the treatment of human breast cancer

• Published in: International journal of nanomedicine 2019-06, Vol.14, p.4105-4121
• Main Authors: Naruphontjirakul, Parichart, Viravaidya-Pasuwat, Kwanchanok
• Format: Article
• Language: English
• Subjects: Animals; Anthracyclines; anti-HER2; Antibodies; Biological products; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer cells; Cancer treatment; Cell Death - drug effects; Cell Survival - drug effects; Cercopithecus aethiops; Chitosan - analogs & derivatives; Chitosan - chemistry; Copolymers; core-shell nanoparticles; doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug delivery systems; Drug Liberation; Drug therapy; EDTA; Female; Humans; Ligands; MCF-7; MCF-7 Cells; Micelles; Monoclonal antibodies; Nanoparticles; Nanoparticles - chemistry; Original Research; Particle Size; Pluronic grafted chitosan; Receptor, ErbB-2 - metabolism; Vero Cells
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S198552

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. 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. 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 IC , which indicated an increase in the therapeutic efficacy of DOX to treat human breast cancer cells with the HER2 overexpression. Our study shows that anti-HER2 conjugated OCP copolymer nanoparticles have the potential for the development of anticancer drug carriers.