An ionic liquid-based delivery system of small interfering RNA targeting Bcl-2 for melanoma therapy
Yuyuan Xing1,2, Yanhui Hu1,2, Hongyan Wang1,2
1Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P. R. China. hyue@ipe.ac.cn.
Abstract:
Melanoma, characterized by rapid tumour progression and a strong tendency to metastasize, poses significant challenges in clinical treatment. Given the vital role of B-cell lymphoma 2 (Bcl-2) protein overexpression in inhibiting apoptosis in tumour cells, the suppression of Bcl-2 has emerged as a promising anticancer therapy. Here, we have developed a straightforward and effective delivery system that combines small interfering RNA (siRNA) targeting Bcl-2 (siBcl-2) with ionic liquids (ILs) for treating melanoma. The unique properties of ILs including structural tunability, inherent charge, and chemical stability have garnered significant attention in the biomedical fields; however, their application in siRNA delivery remains nascent. Rather than the weak function of free siBcl-2, our delivery system (1-hexyl-3-methylimidazolium-siBcl-2, designated as C6-siBcl-2) demonstrated an outstanding capacity to improve the cellular uptake and lysosomal escape, resulting in robust apoptosis and cytotoxicity in melanoma cells. In addition to exhibiting superior gene silencing activity in vitro, such events were also evident in mice bearing melanoma tumours. In particular, this IL-based delivery system showed advantages in suppressing tumour growth, preventing metastasis, and enhancing the survival time of mice with melanoma tumours. Therefore, our study offered a novel and powerful nanoplatform that integrated ILs and RNA interference therapy, presenting new strategies for cancer treatment.
Insights
This study introduces an ionic liquid (IL) delivery system for small interfering RNA (siRNA) targeting B-cell lymphoma 2 (Bcl-2) to treat melanoma. The novel C6-siBcl-2 system effectively suppresses tumor growth and metastasis in mice.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Melanoma exhibits rapid progression and metastasis, posing clinical challenges.
- Overexpression of B-cell lymphoma 2 (Bcl-2) inhibits apoptosis, making its suppression a viable anticancer strategy.
- Ionic liquids (ILs) offer unique properties for biomedical applications, but their use in siRNA delivery is underexplored.
Purpose of the Study:
- To develop and evaluate an ionic liquid-based delivery system for small interfering RNA targeting Bcl-2 (siBcl-2) for melanoma treatment.
- To assess the efficacy of the novel C6-siBcl-2 system in enhancing cellular uptake, promoting apoptosis, and silencing Bcl-2 expression.
- To investigate the therapeutic potential of the IL-siRNA system in a mouse model of melanoma, focusing on tumor suppression, metastasis prevention, and survival.
Main Methods:
- Development of an ionic liquid (1-hexyl-3-methylimidazolium) complexed with siBcl-2 (C6-siBcl-2) for enhanced siRNA delivery.
- In vitro assessment of C6-siBcl-2 in melanoma cells to evaluate cellular uptake, lysosomal escape, apoptosis induction, and gene silencing efficacy.
- In vivo studies using mice bearing melanoma tumors to analyze the effects of C6-siBcl-2 on tumor growth, metastasis, and overall survival.
Main Results:
- The C6-siBcl-2 system demonstrated superior cellular uptake and lysosomal escape compared to free siBcl-2.
- Significant induction of apoptosis and cytotoxicity was observed in melanoma cells treated with C6-siBcl-2.
- In vivo, C6-siBcl-2 effectively suppressed melanoma tumor growth, reduced metastasis, and prolonged survival in mice.
Conclusions:
- The developed IL-based siRNA delivery system (C6-siBcl-2) is a potent platform for melanoma treatment.
- This nanoplatform offers a promising strategy for RNA interference therapy by enhancing siRNA delivery and efficacy.
- The study presents a novel approach for cancer treatment by integrating ILs with RNA interference for improved therapeutic outcomes.
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