Matrix metalloproteinase 2‐responsive dual‐drug‐loaded self‐assembling peptides suppress tumor growth and enhance breast cancer therapy

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli...

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Bibliographic Details
Published in:Bioengineering & translational medicine 2024-11, Vol.9 (6), p.e10702-n/a
Main Authors: Ma, Jihong, Yang, Haiyan, Tian, Xue, Meng, Fanhu, Zhai, Xiaoqing, Li, Aimei, Li, Chuntao, Wang, Min, Wang, Guohui, Lu, Chunbo, Bai, Jingkun
Format: Article
Language:English
Subjects:
Breast cancer
Cancer therapies
Cell death
Chemotherapy
Doxorubicin
drug delivery
Drug delivery systems
Drug dosages
enzyme
Enzymes
High aspect ratio
Immune system
Inflammation
Laboratory animals
Lymphocytes
Matrix metalloproteinases
Morphology
Nanoparticles
Peptides
Polypeptides
Retention
Self-assembly
Sequences
Toxicity
tumor microenvironment
Tumors
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Summary:Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.
ISSN:2380-6761
2380-6761
DOI:10.1002/btm2.10702