Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast...

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Research

Background:

• Small interfering RNA (siRNA) is crucial for targeting undruggable genes and managing metastatic breast cancer.
• Effective siRNA delivery remains a significant challenge for gene silencing therapies.
• Multivalency, a concept in biology, can enhance nanoparticle efficacy through tuned physical parameters.

Purpose of the Study:

• To demonstrate efficient siRNA delivery and gene silencing using multivalent peptide-functionalized gold nanoparticles.
• To investigate the antimetastatic efficacy of these nanoparticles in triple-negative breast cancer cells.
• To compare the performance of multivalent nanoparticles with monovalent free peptide doses.

Main Methods:

• Utilized rod-shaped (aspect ratio: 4) multivalent peptide-functionalized gold nanoparticles for siRNA delivery.
• Assessed gene silencing, toxicity, and antimetastatic effects in MDA-MB-231 and HUVEC cell lines.
• Evaluated *in vitro* epithelial-mesenchymal transition (EMT) progression and *in vivo* antimetastatic activity in a zebrafish model.

Main Results:

• Achieved efficient siRNA delivery and superior gene silencing in MDA-MB-231 cells.
• Demonstrated reduced toxicity of peptide-functionalized nanoparticles.
• Observed prevention of EMT progression and inhibition of metastasis *in vitro* and *in vivo* by silencing Notch1.
• Showcased successful siRNA delivery in hard-to-transfect HUVEC cells.

Conclusions:

• Multivalent peptide-functionalized gold nanoparticles offer an effective strategy for siRNA delivery and gene silencing in breast cancer.
• These nanoparticles exhibit significant antimetastatic potential by inhibiting EMT.
• The structure-activity relationship of multifunctional nanoparticles can be leveraged to enhance biological activity and therapeutic outcomes.