Transformable self-assembling peptide nanoplatforms with tumor microenvironment responsiveness for tumor stem cell...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Breast cancer stem cells (BCSCs) drive tumor growth and treatment resistance.
• The tumor microenvironment supports BCSC stemness and creates immune barriers.
• Current treatments often fail due to BCSC persistence and immune evasion.

Purpose of the Study:

• To develop a novel nanocarrier system for targeted breast cancer therapy.
• To investigate the combined effects of paclitaxel and all-trans retinoic acid delivery.
• To evaluate the nanocarrier's ability to overcome BCSC stemness and immune evasion.

Main Methods:

• Development of an amphiphilic peptide nanocarrier (PA/Pep1) with RGD targeting.
• Encapsulation and pH-responsive release of paclitaxel (PTX) and all-trans retinoic acid (ATRA).
• Assessment of PA/Pep1 effects on BCSC apoptosis, differentiation, immune modulation (TGF-β, IL-6, PD-L1), and drug efflux.

Main Results:

• PA/Pep1 induced breast cancer cell apoptosis and BCSC differentiation, enhancing PTX efficacy.
• The nanocarrier modulated the tumor microenvironment, alleviating immune evasion by reducing TGF-β, IL-6, and PD-L1 expression.
• Acid-triggered transformation of nanocarriers reduced drug efflux and prolonged drug action.

Conclusions:

• PA/Pep1 nanocarriers offer a promising strategy for breast cancer treatment by combining stem cell therapy and immunotherapy.
• The system effectively targets BCSCs and overcomes treatment resistance.
• Novel deformable nanocarrier systems present new therapeutic avenues for breast cancer.