Engineered Exosomes with iRGD Peptide Target Pancreatic Cancer for RNAi Therapy

Pancreatic cancer is one of the most aggressive and lethal malignancies, with a dismal prognosis largely due to late diagnosis and limited effective treatment options. Recent research has highlighted the critical role of long non-coding RNAs (lncRNAs), such as PLBD1-AS1, in promoting cancer cell proliferation and survival. Current therapeutic strategies often lack specificity and encounter significant delivery challenges, leading to systemic toxicity and reduced efficacy. This study addresses the urgent need for a targeted and efficient delivery system for RNA interference (RNAi) therapies to specifically silence oncogenic lncRNAs in pancreatic cancer.

The engineered iRGD-exosomes demonstrated significantly enhanced targeting capabilities, accumulating in pancreatic tumor tissues 3.5-fold higher than unmodified exosomes. In vitro, treatment with PLBD1-AS1 siRNA-loaded iRGD-exosomes led to a 65% reduction in PLBD1-AS1 expression and a 43% decrease in pancreatic cancer cell proliferation (p<0.001) compared to control groups. Furthermore, these exosomes induced a 2.8-fold increase in apoptosis in cancer cells. In vivo, the targeted exosome therapy resulted in a remarkable 68% inhibition of tumor growth and a 55% reduction in tumor volume (p<0.001) in mouse models, significantly extending survival by 30% compared to untreated controls. This therapeutic effect was accompanied by a 72% decrease in tumor cell proliferation markers and a 3.1-fold increase in apoptotic cells within the tumors.