TARGETED DELIVERY of LIGAND-DISPLAYING EXOSOMES USING RNA NANOTECHNOLOGY FOR BREAST CANCER

Breast cancer has been identified as the primary cause of female mortality on a global scale. Recent statistics indicate that a significant number of women, approximately 8.2 million, have been diagnosed with BC in the past five years. Scientists around the world have been motivated to investigate alternative management strategies because of the high prevalence and poor neoadjuvant chemotherapeutic efficacy of BC [1, 2]. Over the last decade, tumor-derived exosomes (TDEs) have been reported in an exponential increase of scientific studies relating to BC pathophysiology and treatment [3]. Exosomes (Exos) are extracellular vesicles that have shown promising results in delivering a payload to cancer cells with great efficacy. Presented in this report are innovative exosomes, adorned with transforming growth factor-α (TGFA), which act as efficient carriers for the targeted delivery of Docetaxel (DTX) and miR155 to breast tumors. This novel approach has demonstrated promising outcomes in inhibiting breast cancer. The Exos targeting capability is facilitated by TGFA, which binds to the overexpressed epidermal growth factor receptors (EGFRs) on the breast cancer cell surface. To achieve specific targeting, a 3-way junction (3WJ) RNA nanoparticle was designed to harbor DTX and miR-155. The 3WJ RNA-DTX complex was then loaded into the Exos, and RNA nanotechnology was employed to decorate its surface with TGFA. The multi-specific Exos have been found to possess the ability to selectively bind and efficiently deliver payload into liver cancer cells. This is due to their unique multi-specific effect of miR155, DTX, TGFA, and Exos, which results in the highest degree of cancer cell inhibition. This research proved that Exos, a natural cargo vehicle, can be effectively used to target difficult-to-treat cancers with anticancer therapeutics. The multi-specific strategy employed reduces the required dose of chemical drugs carried by Exos, indicating high efficiency and low toxicity