Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy

Sara Corvigno1, Yuan Liu1, Emine Bayraktar1,2

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

PubMed

Insights

Plant-derived vesicles (PDVs) offer a novel delivery system for microRNAs (miRNAs) in cancer therapy. This study demonstrates their potential to enhance anti-tumor effects by delivering miRNA146, primarily through anti-angiogenic mechanisms.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Cancer Therapeutics

Background:

  • Small RNAs (miRNAs/siRNAs) show promise for cancer therapy but face delivery challenges like low bioavailability and poor tumor targeting.
  • Extracellular vesicles (EVs) are explored as natural carriers for RNA interference molecules, yet face limitations in cargo loading and scalable production.
  • Plant-derived vesicles (PDVs) are emerging as biocompatible carriers containing biomolecules relevant to biological mechanisms.

Purpose of the Study:

  • To develop an alternative and effective delivery system for microRNA-based cancer therapy using plant-derived vesicles.
  • To formulate a hybrid system combining PDVs with a dendrimer-bound miRNA mimic for enhanced delivery and efficacy.
  • To investigate the in vivo therapeutic efficacy and in vitro anti-tumor mechanisms of the novel miRNA delivery system.

Main Methods:

  • Isolation of vesicles from watermelon (plant-derived vesicles, PDVs).
  • Formulation of a hybrid system using PDVs, a third-generation PAMAM dendrimer, and miRNA146 mimic.
  • In vivo experiments to assess therapeutic efficacy against tumors.
  • In vitro studies to elucidate the anti-tumor mechanisms, focusing on anti-angiogenic activity.

Main Results:

  • Successful formulation of a hybrid PDV-dendrimer-miRNA146 system for targeted delivery.
  • Demonstration of significant in vivo therapeutic efficacy of the developed compound.
  • Identification of anti-angiogenic activity as a primary mechanism underlying the anti-tumor effects of miRNA146.

Conclusions:

  • Plant-derived vesicles represent a promising and innovative platform for delivering therapeutic miRNAs in cancer treatment.
  • The hybrid PDV-dendrimer system enhances miRNA delivery and exhibits potent anti-tumor effects, largely via anti-angiogenesis.
  • This approach overcomes limitations of traditional carriers, offering a scalable and effective strategy for RNA-based cancer therapies.