Issue 22, 2024

Homologous-targeting biomimetic nanoparticles co-loaded with melittin and a photosensitizer for the combination therapy of triple negative breast cancer

Abstract

Melittin (Mel) is considered a promising candidate drug for the treatment of triple negative breast cancer (TNBC) due to its various antitumor effects. However, its clinical application is hampered by notable limitations, including hemolytic activity, rapid clearance, and a lack of tumor selectivity. Here, we designed novel biomimetic nanoparticles based on homologous tumor cell membranes and poly(lactic-co-glycolic acid) (PLGA)/poly(beta-aminoester) (PBAE), denoted MDM@TPP, which efficiently coloaded the cytolytic peptide Mel and the photosensitizer mTHPC. Both in vitro and in vivo, the MDM@TPP nanoparticles effectively mitigated the acute toxicity of melittin and exhibited strong TNBC targeting ability due to the homologous targeting effect of the tumor cell membrane. Under laser irradiation, the MDM@TPP nanoparticles showed excellent photodynamic performance and thus accelerated the release of Mel by disrupting cell membrane integrity. Moreover, Mel combined with photodynamic therapy (PDT) can synergistically kill tumor cells and induce significant immunogenic cell death, thereby stimulating the maturation of dendritic cells (DCs). In 4T1 tumor-bearing mice, MDM@TPP nanoparticles effectively inhibited the growth and metastasis of primary tumors and finally prevented tumor recurrence by improving the immune response.

Graphical abstract: Homologous-targeting biomimetic nanoparticles co-loaded with melittin and a photosensitizer for the combination therapy of triple negative breast cancer

Supplementary files

Article information

Article type
Paper
Submitted
11 Dec 2023
Accepted
28 Apr 2024
First published
14 May 2024

J. Mater. Chem. B, 2024,12, 5465-5478

Homologous-targeting biomimetic nanoparticles co-loaded with melittin and a photosensitizer for the combination therapy of triple negative breast cancer

T. Zhang, L. Bai, R. You, M. Yang, Q. Chen, Y. Cheng, Z. Qian, Y. Wang and Y. Liu, J. Mater. Chem. B, 2024, 12, 5465 DOI: 10.1039/D3TB02919K

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