Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

• Published in: Chemistry : a European journal 2016-01, Vol.22 (5), p.1582-1586
• Main Authors: Ultimo, Amelia, Giménez, Cristina, Bartovsky, Pavel, Aznar, Elena, Sancenón, Félix, Marcos, M. Dolores, Amorós, Pedro, Bernardo, Ana R., Martínez-Máñez, Ramón, Jiménez-Lara, Ana M., Murguía, José R.
• Format: Article
• Language: English
• Subjects: Antibiotics; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; antitumor agents; Apoptosis; Breast cancer; Breast carcinoma; Breast Neoplasms - chemistry; Breast Neoplasms - drug therapy; Cancer; Capping; Cargo; Cell Line, Tumor; Chemistry; Cytotoxicity; Double-stranded RNA; Doxorubicin; Doxorubicin - chemistry; drug delivery; Female; Humans; Immunity; Immunity, Innate; mesoporous gated materials; Nanoparticles; Nanoparticles - chemistry; Ovarian cancer; Poly I-C - chemistry; Poly I-C - pharmacology; Polyinosinic:polycytidylic acid; Ribonucleic acid; RNA; RNA, Double-Stranded - chemistry; RNA, Double-Stranded - pharmacology; Silica; Silicon dioxide; Silicon Dioxide - chemistry; TLR3 protein; Toll-like receptors; Viability
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201504629

We describe herein a Toll‐like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK‐BR‐3 breast carcinoma cells. Our results show that poly(I:C)‐conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA–TLR3 interaction. Such interaction also triggered apoptotic pathways in SK‐BR‐3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles′ mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent. Messenger of death: A new drug‐delivery system based in mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid (poly(I:C)) for targeting breast carcinoma cells is reported (see figure).