pH-responsive self-assembling peptides potentiate ...

Research article

Open access

Under a Creative Commons license

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Highlights

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  The deformable drug-loaded peptide nanocarriers DM/Pep1 targeted breast cancer cells.

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  DM/Pep1 underwent morphological transformation to prolong the retention time of the encapsulated drugs.

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  DM/Pep1 upregulated CD4, induced calreticulin exposure, downregulated PD-L1 and enhanced antitumor immune response.

Abstract

Insufficient drug accumulation at tumor sites is one of the key factors leading to treatment failure in breast cancer (BC), and developing a chemotherapeutic drug delivery system that can improve the immune microenvironment to expand the benefits of immunochemotherapy for BC remains a challenge. To increase the efficacy of BC treatment by extending drug retention at the tumor site, we developed a pH-responsive peptide modified with the PHSCN peptide sequence (Pep1) that self-assembles to form spherical DM/Pep1 nanoparticles after encapsulating doxorubicin (DOX) and metformin (MET). In the acidic tumor microenvironment, spherical nanocarriers transform into aggregates with a high aspect ratio, facilitating DOX and MET release for combined chemotherapy and immunomodulation. In cellular experiments, this construct provided prolonged drug retention in BC cells. In a subcutaneous tumor mouse model, the DM/Pep1 nanoparticles exhibited a superior tumor inhibition effect compared to that of free DOX/MET. The DM/Pep1 nanocomplex upregulated CD4, induced calreticulin (CRT) exposure, downregulated PD-L1, and enhanced the MET-mediated antitumor immune response. The use of this pH-responsive peptide nanocarrier system with morphological transformation offers a promising strategy for BC therapy.

Keywords

pH-responsive

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Peptide self-assembly

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Morphological transformation

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Breast cancer

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Chemotherapy

Data availability

Data will be made available on request.