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VEGF aptamer/i-motif-grafted multi-functional SPION nanocarrier for chemotherapeutic/phototherapeutic synergistic
Bo Fu1, Hui-Chao Lin2,3, Ying-Chun Liu1
1College of Health Industry, Zhongshan Torch Polytechnic, Guangdong, China.
Abstract:
Chemotherapeutic agents and photosensitizers often suffer from poor tumor selectivity, high side toxicity, or low water solubility. To address these problems, various drug delivery systems (DDS) have been explored but most of them are toxic, difficult to synthesize, or of single function. In order to design a highly biocompatible, conveniently prepared, multi-functional drug delivery system, herein, an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-DNA fragment were grafted on the surface of superparamagnetic iron oxide nanoparticles (SPION), and then a chemotherapeutic agent daunomycin (DNM) and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were self-assembled with the hybridized VEGF-based DNA structure. By loading DNM and TMPyP, the DDS displayed strong chemotherapeutic/phototherapeutic capability against cancer cells via mechanisms such as mitochondrial dysfunction and ROS elevation, which triggered the apoptosis of the tumor cells. The dual delivery of chemotherapeutical agents and photosensitizers with aptamer/C-rich DNA successfully integrated the functions of pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system and thus could be considered as an ideal drug delivery vehicle with great potential in clinic.
Insights
This study presents a novel multi-functional drug delivery system using superparamagnetic iron oxide nanoparticles. This system effectively delivers chemotherapy and phototherapy agents to cancer cells, enhancing treatment efficacy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Conventional chemotherapy and phototherapy face challenges like poor tumor selectivity and high toxicity.
- Existing drug delivery systems (DDS) often exhibit toxicity, complex synthesis, or limited functionality.
Purpose of the Study:
- To develop a highly biocompatible, easily prepared, and multi-functional DDS for enhanced cancer treatment.
- To integrate chemotherapy and phototherapy with targeted delivery and stimuli-responsive release.
Main Methods:
- Grafting vascular endothelial growth factor (VEGF) aptamer and cytosine (C)-DNA onto superparamagnetic iron oxide nanoparticles (SPION).
- Self-assembling chemotherapeutic daunomycin (DNM) and photosensitizer TMPyP with the hybridized VEGF-DNA structure.
- Utilizing SPION for targeted delivery and pH-responsive drug release.
Main Results:
- The DDS demonstrated potent chemotherapeutic and phototherapeutic capabilities against cancer cells.
- The system induced cancer cell apoptosis through mitochondrial dysfunction and reactive oxygen species (ROS) elevation.
- Successful integration of dual drug delivery, pH-responsive release, and combined therapeutic modalities.
Conclusions:
- The developed aptamer-SPION-based DDS offers a promising, multi-functional platform for cancer therapy.
- This system overcomes limitations of traditional treatments by enhancing selectivity and efficacy.
- The integrated approach holds significant potential for clinical applications in cancer treatment.
