Enhancing the Management of Metastatic Tumors by Robust Co‐Delivery of 5‐Fluorouracil/MicroRNA‐10b Inhibitor Using EGFR‐Targeted Nanovehicles

Abstract

Invasion and metastasis are the leading causes of death of patients with CRC. 5-Fluorouracil is widely used in clinic practice as the basic chemotherapy drug for CRC. However, it is inefficient in inhibiting tumor metastasis. MicroRNA-10b is uninvolved in regulating the growth of primary tumors; however, it could induce early tumor metastases and is a key regulator of chemotherapeutic resistance to 5-FU. A multifunctional nanovehicle that can carry small molecule drugs not only through the hydrophobic pockets of conjugated 𝜷-cyclodextrin but also through electrostatic interaction between the conjugated peptides and siRNA to target functional genes is previously developed. In this study, a nanovehicle, named GCD, with epithelium growth factor receptor (EGFR)-targeted characteristics to simultaneously deliver chemotherapeutic and nucleotide drugs to distinct targets in CRC, is employed. These data show that co-delivery of 5-FU and anti-miR-10b can be effectively applied to targeted therapy of EGFR-overexpressed CRC, particularly inhibiting the metastasis of CRC. Furthermore, the therapeutic effect of this combination on tumor xenograft models derived from patients with CRC is evaluated. Taken together, this study may provide insights into the inhibition of tumor growth and metastasis simultaneously.

Folate-Targeted Nanocarriers Co-Deliver Ganciclovir and miR-34a-5p for Combined Anti-KSHV Therapy

“…Many studies have reported that positively charged materials can be combined with negatively charged genes and nucleic acids through electrostatic adsorption to form drug-carrying nanocomplexes for the effective delivery of genes and nucleic acids [ 36 ]. Wang et al [ 37 ] prepared a multifunctional nanoparticle based on quantum dots (CDs) and modified β-cyclodextrin (β-CD) and arginine-glycine–aspartate (RGD) peptides. The nanocarrier can not only carry the small-molecule chemotherapeutic drug 5-fluorouracil (5-FU) through the hydrophobic cavity of β-CD, but also adsorb the electronegative siRNA (miR-10b inhibitor) through the positive electronegativity of the RGD peptide.…”