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Establishment of MicroRNA delivery system by PP7 bacteriophage-like particles carrying cell-penetrating peptide

Yanli Sun1, Yanhua Sun2, Ronglan Zhao1

  • 1Institute of Nanomedicine Technology, Department of Laboratory Medicine, Institutional Key Laboratory of Clinical Laboratory Diagnostics, 12th 5-Year Project of Shandong Province, Key Discipline of Clinical Laboratory Medicine of Shandong Province, Affiliated Hospital of Weifang Medical University, Weifang Medical University, Weifang 261053, China.

Journal of Bioscience and Bioengineering
|April 27, 2017
PubMed

Insights

Recombinant bacteriophage virus-like particles (VLPs) offer a novel method for delivering microRNAs (miRNAs) into cancer cells. These engineered VLPs protect miRNAs from degradation and enhance cellular uptake, showing potential for targeted cancer therapy.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Nanomedicine

Background:

  • MicroRNAs (miRNAs) show therapeutic promise but face challenges with instability and inefficient in vivo delivery.
  • Existing delivery methods, including viral and non-viral vectors, have limitations.

Purpose of the Study:

  • To develop a novel delivery system for microRNAs using recombinant PP7 bacteriophage virus-like particles (VLPs).
  • To enhance microRNA delivery efficiency and stability for potential therapeutic applications in cancer treatment.

Main Methods:

  • Engineered recombinant PP7 bacteriophage-based VLPs to package specific exogenous pre-microRNAs via the pac site.
  • Incorporated a cell-penetrating peptide (CPP) into the VLP structure to improve mammalian cell penetration.
  • Utilized a one-plasmid double expression system in Escherichia coli for efficient VLP production.
  • Tested the delivery of pre-microRNA-23b into hepatoma SK-HEP-1 cells and assessed its therapeutic effect.

Main Results:

  • PP7 VLPs carrying a CPP successfully delivered pre-microRNA-23b into hepatoma cells, with mature miRNA processed within 24 hours.
  • A concentration of 10 nM PP7 VLPs with CPP inhibited hepatoma cell migration by downregulating liver-intestine cadherin expression.
  • The engineered PP7 VLPs demonstrated no infectious, replicative, or cytotoxic effects.

Conclusions:

  • Recombinant PP7 VLPs with CPP provide a stable and efficient platform for targeted microRNA and peptide delivery.
  • This system overcomes limitations of traditional delivery methods and shows potential for simultaneous delivery of therapeutic payloads.
  • The non-infectious, non-replicative, and non-cytotoxic nature of these VLPs supports their safety for therapeutic development.
Keywords:
CDH17Cell-penetrating peptidesHepatoma cellsLiver-intestine cadherinMicroRNAMigrationPP7 bacteriophage

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