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Membrane Protein-Binding and Membrane-Inserting Chimeras for Cancer Therapy.

Jiamin Cai1, Sujuan Wang1, Aili Zhou1

  • 1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, People's Republic of China.

Bioconjugate Chemistry
|September 16, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces novel membrane protein-targeting and membrane-inserting (MBI) chimeras for enhanced cancer theranostics. These MBI chimeras improve drug delivery and photodynamic therapy efficacy in acidic tumor microenvironments.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nanotechnology

Background:

  • Aptamers and antibodies are crucial for cancer theranostics but struggle with tumor retention due to noncovalent interactions.
  • The acidic tumor microenvironment poses challenges for drug accumulation and therapeutic effectiveness.

Purpose of the Study:

  • To develop novel membrane protein-targeting and membrane-inserting (MBI) chimeras for improved cancer theranostics.
  • To enhance the delivery of therapeutic agents like chlorin e6 (Ce6) into tumor cells.
  • To overcome limitations of traditional molecular recognition tools in tumor microenvironments.

Main Methods:

  • Conjugation of a membrane protein-targeting aptamer with a pH-responsive membrane-inserting domain (pHLIP).
  • Creation of MBI chimeras designed to target tumor cells in acidic environments.
  • In vivo evaluation of Ce6-loaded MBI chimeras (Sgc8-pHLIP) for photodynamic therapy efficacy.

Main Results:

  • MBI chimeras demonstrated efficient binding to tumor cells in acidic conditions.
  • Sgc8-pHLIP showed significantly enhanced photodynamic therapeutic efficacy compared to control constructs.
  • The synergistic effect of membrane targeting and insertion improved drug delivery and retention.

Conclusions:

  • MBI chimeras represent a promising strategy for precise cancer therapeutics.
  • This approach enhances the efficiency of molecular recognition tools for cancer treatment.
  • The study highlights the potential of combining targeting and membrane insertion for improved theranostics.