title: Rituximab-conjugated and doxorubicin-loaded microbubbles combined with ultrasound irradiation inhibits proliferation and induces apoptosis in Raji cell lines.
abstract: Doxorubicin (DOX) is one of the most important medicines used for the treatment for B cell lymphoma, yet its clinical efficacy is often limited by severe adverse effects. Drug-loaded microbubbles, combined with ultrasound (US) irradiation, has shown great promise in reducing DOX-induced side effects and improving therapeutic efficacy. Nevertheless, these drug-loaded microbubbles are non-targeted microbubbles with comparatively suboptimal efficiency. Therefore, we synthesized targeted and DOX-loaded microbubbles (DMs), combined with US irradiation, for triggering drug release in lymphoma B cells. DMs were coated with rituximab via a biotin-avidin linkage to target Raji cells that overexpress the CD-20 antigen. In the present study, the cell viability after treatment with rituximab-conjugated DMs (RDMs) containing 0.25, 0.5 and 1.0 µg/ml DOX + US was 45.69±6.85, 25.31±2.60 and 15.67±2.83%, respectively, which demonstrated that RDMs + US produced significantly higher cytotoxicity than the other treatments. The early apoptosis ratio in the Raji cells at 48 h after the treatment was 32.4±2.84%, which was notably higher than the ratio in the other treatment groups. The results confirm the hypothesis that US-mediated targeting of CD-20-positive B cell lymphoma and the use of DMs may improve the DOX therapeutic efficiency.
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shoubing
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shiya
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, P.R. China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Cailian
authors.initials: C
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D045423:Microbubbles / Q000627:therapeutic use*; D000069283:Rituximab / Q000008:administration & dosage*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D000069283:Rituximab; D004317:Doxorubicin