Therapeutic nanosystems co-deliver anticancer drugs and oncogene SiRNA to achieve synergetic precise cancer chemo-gene therapy

Abstract

Co-delivering a chemotherapeutic agent and cancer-specific small interfering RNA (siRNA) as a new therapeutic modality provides a promising strategy for cancer treatment. In this study, we designed and described a cancer-target and pH-sensitivity nanosystem (RGD-SeNPs/siRNA) which has a DOX-loaded SeNPs core and c-myc siRNA-delivered PAMAM-RGD decoration for combination therapy against glioblastoma. The nanosystem exhibited high stability in water and FBS solutions for a long time. PAMAM-RGD surface decoration significantly enhanced the cellular uptake of RGD-SeNPs/siRNA and increased the selectivity between normal and cancer cells. More importantly, the nanosystem expanded to petaloid particles under pH 5.3 circumstance, which prolonged the duration of drugs after ingestion and reduced undesirable side effects. In addition, a blood-brain barrier (BBB) model we established in vitro revealed the nanosystem effectively penetrated BBB and enhanced antitumor activity. Moreover, the nanosystem also exhibited excellent advantages in penetrating ability and inhibitory effects on U251 tumor spheroids, demonstrating its in vivo anticancer potential. Therefore, this study provides a strategy for the design of cancer-targeted nanoplatforms as carriers of oncogene siRNA and chemotherapeutics to achieve synergistic cancer therapy.