Evidence map›Paper›PMID 39525569›Full record

ArticleActa pharmaceutica Sinica. B2024

Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins.

Yan Zhao, Haolin Jiang, Hang Chen, Jiazhen Yu, Luyao Wang, Wen Zhou, Juanjuan Du

Abstract read
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In one paragraph

Article in Acta pharmaceutica Sinica. B, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yan ZhaoSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Haolin JiangSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Hang ChenSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Jiazhen YuSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Luyao WangSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Wen ZhouSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.
Juanjuan DuSchool of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2

Indexed as

AntibodyCell-penetrating peptidesCytosolic deliveryElectrostatic maskingEndosomal escapeLMWPpH responsivenessTargeted delivery

Identifiers

PMID39525569
PMCPMC11544179

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.