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Related Experiment Video

Updated: Jan 16, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
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A Dual-Action Liposome-Peptide Formulation Synergistically Counteracts A Gain-of-Function p53 Mutant.

Sneha Ghosh Chaudhary, Swati Bhowmick, Samriddhi Bhattacharya

    Biorxiv : the Preprint Server for Biology
    |October 1, 2025
    PubMed
    Summary

    A novel liposome-encapsulated peptide targeting p53R273H mutations enhances doxorubicin efficacy in cancer cells. This formulation offers a promising strategy for overcoming drug resistance in tumors with this common p53 mutation.

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    Area of Science:

    • Oncology
    • Molecular Biology
    • Drug Delivery

    Background:

    • Gain-of-function p53 mutations, like R273H, drive cancer progression and drug resistance.
    • The p53R273H mutant protein interacts with Positive Coactivator 4 (PC4), essential for its oncogenic functions.
    • Existing therapies are often ineffective against tumors harboring p53R273H mutations.

    Purpose of the Study:

    • To develop and evaluate a novel therapeutic formulation for p53R273H-mutant cancers.
    • To investigate the potential of a PC4-targeting peptide encapsulated in cationic liposomes (PC-SA) to enhance anti-cancer drug efficacy.

    Main Methods:

    • Synthesis of the NLS-p53(380-386) peptide and its encapsulation into PC-SA liposomes.
    • Assessment of biological effects using MTT assays, confocal microscopy, flow cytometry, qRT-PCR, and Western blotting.
    • Evaluation of enhanced chemosensitivity to doxorubicin in p53R273H-mutant cancer cell lines.

    Main Results:

    • The liposome-encapsulated peptide significantly enhanced doxorubicin-induced cancer cell death.
    • Pre-treatment with the encapsulated peptide was more effective than the free peptide or liposome alone.
    • The formulation demonstrated improved efficacy in overcoming drug resistance associated with the p53R273H mutation.

    Conclusions:

    • Liposome-encapsulated NLS-p53(380-386) peptide is a promising strategy for treating p53R273H-mutant cancers.
    • This formulation improves the delivery and efficacy of anti-cancer therapies.
    • Further development could lead to novel interventions for resistant tumors.