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Engineered tumor microvesicles modified by SP94 peptide for arsenic trioxide targeting drug delivery in liver cancer
Faisal Raza1, Mengyuan Zheng1, Hongyu Zhong1
1School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Abstract:
Liver cancer is among the leading cause of cancer related death worldwide. There is growing interest in using traditional Chinese medicines such as arsenic trioxide (ATO) to treat liver cancer. ATO have attracted attention due to its wide range of anti-cancer activities. However, the current ATO formulations are associated with drawbacks such as short half-life, lack of targeting ability towards solid tumors and apparent toxic side effects. Tumor microvesicles (TMVs) has shown encouraging results for the delivery of drugs to solid tumor. In this work, we designed ATO loaded TMVs further modified by SP94 peptide as liver cancer specific ligand (ATO@SP94-TMVs). This drug delivery system utilized SP94 peptide that selectively targets liver cancer cells while TMVs increase the accumulation of ATO at tumor site and activate immune response owing to the associated antigens. ATO@SP94-TMVs exhibited high encapsulation efficiency and tumor microenvironment triggered enhanced release of ATO in vitro. Cytotoxicity and uptake studies revealed remarkable inhibition and specific targeting of H22 cells. In addition, excellent immune response was detected in vitro, enhancing anti-tumor efficacy. Furthermore, a tumor inhibition rate of about 53.23 % was observed in H22 bearing tumor model. Overall, these results confirm that ATO@SP94-TMVs can be a promising nano drug delivery system for the future liver cancer therapy and improve its clinical applications.
Insights
Arsenic trioxide loaded tumor microvesicles modified with SP94 peptide show promise for liver cancer therapy. This targeted nano-drug delivery system enhances anti-tumor efficacy and reduces side effects.
Area of Science:
- Oncology
- Nanotechnology
- Drug Delivery
Background:
- Liver cancer is a leading cause of cancer-related death globally.
- Traditional Chinese medicines like arsenic trioxide (ATO) show anti-cancer potential but face formulation challenges.
- Existing ATO formulations have short half-lives, poor tumor targeting, and significant toxicity.
Purpose of the Study:
- To develop a novel drug delivery system for liver cancer using ATO loaded tumor microvesicles (TMVs) modified with a liver cancer-specific ligand (SP94 peptide).
- To evaluate the targeting ability, efficacy, and immune-activating properties of the designed ATO@SP94-TMVs.
- To assess the potential of ATO@SP94-TMVs as an improved therapeutic strategy for liver cancer.
Main Methods:
- Design and synthesis of SP94 peptide-modified, ATO-loaded TMVs (ATO@SP94-TMVs).
- In vitro evaluation of encapsulation efficiency, drug release kinetics, cytotoxicity, and cellular uptake in H22 liver cancer cells.
- Assessment of in vitro immune response and in vivo anti-tumor efficacy in a H22 tumor-bearing mouse model.
Main Results:
- ATO@SP94-TMVs demonstrated high encapsulation efficiency and triggered release of ATO in the tumor microenvironment.
- Significant inhibition of H22 cell proliferation and specific targeting were observed in vitro.
- Enhanced immune response and a tumor inhibition rate of 53.23% were achieved in vivo.
- The SP94 peptide facilitated selective targeting of liver cancer cells.
Conclusions:
- ATO@SP94-TMVs represent a promising nano-drug delivery system for liver cancer therapy.
- This system overcomes limitations of conventional ATO formulations by improving targeting and reducing toxicity.
- Further clinical applications of this targeted nanomedicine for liver cancer are warranted.
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