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Background <p>Low molecular weight protamines (LMWPs) are short polycationic peptides that have been utilized for cellular delivery of biodrugs and nucleic acids or as a part of nanopharmaceutical drug delivery systems. Despite the potential impact of LMWPs for biopharmaceutical applications, its intracellular trafficking in human cells is still not fully understood. In this study, we compared the cellular uptake efficiency, intracellular trafficking and subcellular localization of the LMWP (TDSP4) in various types of human tumor and non-tumor cell lines.</p> Methods and results <p>Our findings demonstrate that the peptide could be rapidly internalized (within 15&#xa0;min) in all tested cell lines. Also, time-lapse live-cell imaging experiments revealed that the peptide mainly traffics from the plasma membrane to the nuclear/nucleolar compartment, with a notable substantial time-dependent increase in the peptide-nuclear accumulation but at different rates based on the type of cells.</p> Conclusions <p>At the first time, LMWP peptide subcellular trafficking has been explored in tumor and non-tumor cell lines. This report provides an important preliminary understanding of the dynamic cellular trafficking of the LMWP which can help in the development of potential peptide-based therapeutics in the future.</p>

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Comparison of subcellular trafficking of the low molecular weight protamine (LMWP) fragment in tumor and non-tumor cells

  • 期刊论文

  • 发表日期：

    2026年1月21日

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  • Ismail Sami Mahmoud,
  • Majed Al Holi,
  • Duaa Abuarqoub,
  • Walhan Alshaer

摘要

Background

Low molecular weight protamines (LMWPs) are short polycationic peptides that have been utilized for cellular delivery of biodrugs and nucleic acids or as a part of nanopharmaceutical drug delivery systems. Despite the potential impact of LMWPs for biopharmaceutical applications, its intracellular trafficking in human cells is still not fully understood. In this study, we compared the cellular uptake efficiency, intracellular trafficking and subcellular localization of the LMWP (TDSP4) in various types of human tumor and non-tumor cell lines.

Methods and results

Our findings demonstrate that the peptide could be rapidly internalized (within 15 min) in all tested cell lines. Also, time-lapse live-cell imaging experiments revealed that the peptide mainly traffics from the plasma membrane to the nuclear/nucleolar compartment, with a notable substantial time-dependent increase in the peptide-nuclear accumulation but at different rates based on the type of cells.

Conclusions

At the first time, LMWP peptide subcellular trafficking has been explored in tumor and non-tumor cell lines. This report provides an important preliminary understanding of the dynamic cellular trafficking of the LMWP which can help in the development of potential peptide-based therapeutics in the future.