AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells

Area of Science:

• Nanomedicine
• Cancer Biology
• Gene Therapy

Background:

• Advanced cancers are sustained by cancer stem cells (CSCs), which drive metastasis and drug resistance.
• Developing effective RNA interference (RNAi) therapies with a suitable therapeutic window for advanced cancers remains a significant challenge.
• Targeting CSCs is crucial for developing novel, effective anticancer therapies.

Purpose of the Study:

• To design and characterize a novel amphiphilic-based gene delivery system for RNAi.
• To evaluate the efficacy of this system loaded with siRNA against AKT2 in breast cancer stem cells.
• To investigate AKT2 inhibition as a therapeutic strategy against CSCs.

Main Methods:

• A Pluronic F127 micelle and polyethylenimine (PEI) 10K polyplex-based nanocarrier (PM) was developed.
• siRNA targeting the oncogene AKT2 (siAKT2) was loaded into the PM system (siAKT2-PM).
• The efficacy of siAKT2-PM was tested on CSCs isolated from MCF-7 and Triple Negative MDA-MB-231 breast cancer cell lines.

Main Results:

• The developed PM system demonstrated favorable physicochemical characteristics, cellular uptake, and a good toxicity profile for siRNA transport.
• Treatment with siAKT2-PM significantly reduced the invasive capacity of CSCs from both cell lines.
• siAKT2-PM treatment strongly inhibited mammosphere formation in both CSC populations.

Conclusions:

• AKT2 is a potent therapeutic target for combating cancer stem cells in breast cancer.
• The developed nanomedicine-based gene delivery system shows promise for advanced cancer treatment by targeting CSCs.
• This approach paves the way for more effective nanomedicine-based gene therapies to prevent CSC-driven tumor recurrence.