Multifunctional nanoparticle for effective cancer treatment

Abstract

Polymer-metallic multi-layer half-shell nanoparticles (H-S NPs) are developedas multi-functional nanoplatform for simultaneous delivery of drug and heat, andmagnetic resonance imaging (MRI) enhancement. These nanoparticles arefabricated by depositing Mn and Au films onto doxorubicin-loaded poly(lactic-coglycolic)(PLGA) nanoparticles and their surface plasmon-resonance frequency isfound to be in the near infrared (NIR) range. Drug release from PLGAnanoparticles is enhanced upon NIR irradiation, which is converted into thermalenergy. For the targeted delivery, targeting moieties such as antibodies againsttumor maker proteins are conjugated on the gold surface, allowing the delivery ofheat and drugs to the targeted region. In addition, the magnetic properties of theMn layer allow these nanoparticles to act as MRI contrast agents.Drug-loaded PLGA Au H-S NPs can be used for delivery of drug and heat to theselected tumor. In order to investigate therapeutic efficacy of the nanoparticles, I carried out in vitro and in vivo experiments. For in vitro experiments, humancervical cancer (HeLa) cell line was used and therapeutic efficacy was concludedby measuring cell viability. For in vivo experiments, prepared tumor bearing miceby implanting human epidermoid carcinoma (A431) cells or human breast cancer(sk-br-3) cell, therapeutic efficacy was concluded by measuring tumor volumechange. Compared with chemotherapy or photothermal treatment alone, thecombined treatment demonstrated higher therapeutic efficacy. In the histologicalexaminations of tumor tissues treated with chemo-photothermal therapy, I find thatthermonecrosis and apoptosis are developed. The proliferating cell nuclear antigen(PCNA) assay shows that most cells are unable to proliferate following chemophotothermaltreatments. When the remaining NPs are measured by using ICPmass, most NPs have been cleared from the mice for 28 days after injection. It isconfirmed that NPs do not result in immune response and liver toxicity bymeasuring the interlukein-6 (IL-6), aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in blood.