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Updated: Jan 28, 2026
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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
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pH-responsive polymeric-peptide complex enhances tumor immunogenic cell death by membrane disruption
Guanyu Jin1, Zhaofan Yang1, Lanqing Wang1
1School of Materials Science and Engineering and Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Peking University, Beijing 100871, PR China.
Summary
A novel pH-responsive polymeric-peptide complex (PCM) delivers melittin to tumors, enhancing anticancer effects and reducing toxicity. This targeted approach activates immune responses and inhibits cancer recurrence in preclinical models.
Area of Science:
- Biochemistry
- Nanotechnology
- Immunology
Background:
- Melittin, a bee venom peptide, shows promise as an anticancer agent.
- Nonspecific hemolytic toxicity limits melittin's clinical use.
- Targeted delivery systems are needed to improve melittin's therapeutic index.
Purpose of the Study:
- To develop a pH-responsive polymeric-peptide complex (PCM) for targeted melittin delivery.
- To enhance melittin's anti-tumor activity while minimizing off-target toxicity.
- To investigate the immune-activating potential of PCM-mediated tumor cell death.
Main Methods:
- Fabrication of a pH-responsive polymeric-peptide complex (PCM).
- In vitro assessment of PCM stability and melittin release at different pH values.
- Evaluation of PCM's cytotoxicity and membrane disruption effects on tumor cells.
- In vivo efficacy studies in a murine breast cancer model, assessing tumor recurrence, metastasis, and immune memory.
Main Results:
- PCM demonstrated structural stability at pH 7.4 and rapid disassembly at tumor-relevant pH 6.8.
- Released melittin effectively disrupted tumor cell membranes, inducing cell death and releasing damage-associated molecular patterns (DAMPs).
- Low-dose PCM administration significantly inhibited tumor recurrence and metastasis in mice, establishing durable antitumor immunological memory with minimal side effects.
Conclusions:
- The pH-responsive PCM system enables targeted delivery of melittin, enhancing its anticancer efficacy.
- PCM-induced membrane disruption not only kills tumor cells but also potentiates antitumor immune responses.
- This strategy offers a promising approach for the clinical translation of anticancer peptides with improved safety and efficacy profiles.
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