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Published on: December 1, 2016
Development of a reactive oxygen species (ROS)-responsive nanoplatform for targeted oral cancer therapy
1School of Stomatology, Shandong University, Jinan, Shandong 250012, P. R. China. xinxu@sdu.edu.cn.
Abstract:
In this study, for effective oral cancer therapy, a new targeted and ROS-triggered drug delivery nanoplatform was developed from the RGD-PEG-TK-PLGA polymer, in which the ROS-responsive TK containing linker was connected with PEG and PLGA. RGD in the drug delivery system (DDS) presented here was used to target cancer cells. This new nanoplatform shows high stability, good targeting ability, excellent ROS sensitivity and excellent biocompatibility. Loaded with DOX and alpha-TOS, the formulated nanoparticles (NPs) demonstrate much better cellular uptake efficiency and higher inhibition performance towards the oral tongue Cal27 cancer cell line. In vivo anticancer evaluation indicates that DOX and alpha-TOS loaded RGD-PEG-TK-PLGA NPs have no toxicity to mice and showed significantly improved therapeutic efficacy against tumors. Therefore, this polymeric NP platform presents great potential as a new DDS for oral cancer chemotherapy.
Insights
A novel RGD-PEG-TK-PLGA nanoplatform effectively targets oral cancer cells. This drug delivery system (DDS) shows high stability, biocompatibility, and enhanced therapeutic efficacy against tumors with no observed toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Oral cancer poses a significant therapeutic challenge, necessitating advanced drug delivery systems (DDS).
- Current DDS often lack targeted delivery and responsiveness to the tumor microenvironment, limiting efficacy and increasing side effects.
Purpose of the Study:
- To develop a novel, targeted, and reactive oxygen species (ROS)-triggered nanoplatform for enhanced oral cancer therapy.
- To evaluate the efficacy and safety of this nanoplatform loaded with doxorubicin (DOX) and alpha-tocopherol succinate (alpha-TOS) in oral cancer models.
Main Methods:
- Synthesis of a RGD-PEG-TK-PLGA polymer nanoplatform incorporating a ROS-sensitive linker (TK).
- Characterization of nanoplatform stability, targeting ability, ROS sensitivity, and biocompatibility.
- In vitro evaluation of cellular uptake and inhibition of Cal27 oral cancer cells loaded with DOX and alpha-TOS.
- In vivo assessment of therapeutic efficacy and toxicity in mouse tumor models.
Main Results:
- The RGD-PEG-TK-PLGA nanoplatform demonstrated high stability, excellent targeting, ROS sensitivity, and biocompatibility.
- Nanoparticles (NPs) loaded with DOX and alpha-TOS exhibited enhanced cellular uptake and significant inhibition of Cal27 oral cancer cells.
- In vivo studies showed no toxicity in mice and a significant improvement in therapeutic efficacy against oral tumors.
Conclusions:
- The developed RGD-PEG-TK-PLGA polymeric NP platform is a promising DDS for oral cancer chemotherapy.
- Its targeted and ROS-triggered nature, combined with effective drug loading, offers a potent strategy for improving treatment outcomes.
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