pH-Triggered Transformable Peptide Nanocarriers Extend Drug Retention for Breast Cancer Combination Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Effective chemotherapy requires enhanced drug penetration and accumulation at tumor sites.
• Cancer stem cells (CSCs) drive tumor initiation, progression, and metastasis.
• Existing treatments face challenges with drug delivery and CSC resistance.

Purpose of the Study:

• To develop a peptide-based nanodelivery system for combined chemotherapy.
• To investigate the tumor-responsive transformation and drug accumulation of the nanodelivery system.
• To evaluate the efficacy of the system in targeting CSCs and inhibiting tumor metastasis.

Main Methods:

• Design and synthesis of a peptide (Pep1) loaded with cis-diamminedichloroplatinum (DDP) and all-trans retinoic acid (ATRA).
• Self-assembly of the peptide into spherical nanoparticles (NPs) in a neutral environment.
• Observation of NP transformation into sheet-like aggregates in an acidic tumor microenvironment.

Main Results:

• The DDP- and ATRA-loaded Pep1 (DA/Pep1) NPs demonstrated enhanced accumulation in acidic tumor environments.
• The transformed aggregates significantly increased antitumor effects and inhibited metastasis.
• ATRA induced CSC differentiation, enhancing the therapeutic effect of DDP against breast cancer.

Conclusions:

• The developed peptide nanodelivery system exhibits tumor-responsive transformation, improving drug delivery and efficacy.
• This nanoplatform offers a promising strategy for combined chemo- and CSC-targeting therapy.
• The system represents a novel approach for overcoming challenges in cancer treatment and metastasis inhibition.