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Genetically multimodal therapy mediated by one polysaccharides-based supramolecular nanosystem
Chen Xu1, Wenting Hu1, Na Zhang1
1Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
This study introduces a novel nanosystem for combined photodynamic and gene therapy, overcoming limitations of traditional methods. The new system demonstrates enhanced antitumor effects, offering a promising strategy for cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Multimodal cancer therapy, particularly photodynamic/gene combined therapy, shows promise but faces challenges with traditional photosensitizers and therapy asynchronism.
- Developing integrated nanosystems is crucial for overcoming these limitations and improving therapeutic outcomes.
Purpose of the Study:
- To design and evaluate a genetically multimodal treatment nanosystem (HES@PGEA/pKR-p53) for enhanced synergistic cancer therapy.
- To address the limitations of traditional photosensitizers and therapy asynchronism in combined photodynamic and gene therapy.
Main Methods:
- Structural design of the nanosystem using host-guest assembly and electrostatic complexing with hydroxyethyl starch (HES), β-cyclodextrin-based ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA), and pKR-p53 plasmid.
- Evaluation of HES@PGEA's biocompatibility, cellular internalization, and gene transfection efficiency.
- Assessment of the nanosystem's antitumor efficacy in a 4T1 tumor model, analyzing the synergistic effects of p53-mediated apoptosis and photodynamic therapy (PDT).
Main Results:
- The supramolecularly assembled HES@PGEA demonstrated low cytotoxicity, excellent cellular uptake, and enhanced gene transfection.
- Simultaneous expression of p53 and KillerRed proteins within tumor cells was achieved, enabling combined apoptosis and PDT.
- The HES@PGEA/pKR-p53 nanosystem exhibited significantly superior antitumor effects compared to single-therapy approaches in the 4T1 tumor model.
Conclusions:
- The developed HES@PGEA/pKR-p53 nanosystem effectively integrates gene therapy and photodynamic therapy.
- This multimodal nanosystem offers a promising strategy for synergistic cancer treatment with enhanced antitumor efficacy.
