An ionic liquid-based delivery system of small interfering RNA targeting Bcl-2 for melanoma therapy.

in Biomaterials science by Yuyuan Xing, Yanhui Hu, Hongyan Wang, Yanyan Diao, Hua Yue

TLDR

  • Researchers developed a novel delivery system combining small interfering RNA targeting Bcl-2 with ionic liquids to treat melanoma, demonstrating improved efficacy and potential for cancer treatment.

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, 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.

Overview

  • Study focuses on developing a delivery system to target Bcl-2 protein overexpression in melanoma, a highly aggressive form of skin cancer.
  • The study combines small interfering RNA (siRNA) targeting Bcl-2 with ionic liquids (ILs) to improve cellular uptake and lysosomal escape.
  • The primary objective is to suppress tumour growth, prevent metastasis, and enhance the survival time of mice with melanoma tumours.

Comparative Analysis & Findings

  • Compared to free siBcl-2, the IL-based delivery system, C6-siBcl-2, demonstrated improved cellular uptake and lysosomal escape, leading to enhanced gene silencing activity, apoptosis, and cytotoxicity in melanoma cells.
  • In vivo experiments in mice bearing melanoma tumours showed that the C6-siBcl-2 delivery system inhibited tumour growth, prevented metastasis, and increased survival time compared to the control group.
  • The study highlights the potential of ILs as a novel delivery system for RNA interference therapy, offering a new strategy for cancer treatment.

Implications and Future Directions

  • The findings of this study open up new avenues for the treatment of melanoma, a highly aggressive and metastatic disease that poses significant challenges in clinical treatment.
  • Future studies should investigate the potential of IL-based delivery systems for other types of cancer and explore the optimal combination of ILs and siRNA sequences for enhanced therapeutic efficacy.
  • The use of ILs in RNA interference therapy may provide a promising approach for the treatment of various diseases beyond cancer, warranting further exploration and development.
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