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Functional micro-RNA drugs acting as a fate manipulator in the regulation of osteoblastic death

Zhengwen Cai1,2, Fengshuo Liu1, Yong Li1,2

  • 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. sirongshi@scu.edu.cn.

Nanoscale
|July 24, 2023
PubMed

Insights

Regulated cell death (RCD) influences bone diseases like osteoporosis. A novel tetrahedral DNA nanostructure (TDN) delivers microRNAs (miRNAs) to target RCD pathways, offering a promising therapeutic strategy for bone loss.

Area of Science:

  • Biomedical Engineering
  • Molecular Biology
  • Nanotechnology

Background:

  • Bone loss, exemplified by osteoporosis, involves impaired osteoblast function, increased osteoclast activity, and disrupted bone homeostasis.
  • Current treatments for bone diseases are limited, highlighting the need for innovative therapeutic approaches.
  • Regulated cell death (RCD) pathways are implicated in bone diseases, suggesting that modulating osteoblast fate could be a viable treatment strategy.

Purpose of the Study:

  • To explore the role of microRNA (miRNA) networks in regulating key RCD programs (apoptosis, autophagy, pyroptosis, ferroptosis) within bone tissues.
  • To introduce a novel self-assembling tetrahedral DNA nanostructure (TDN)-based microRNA (Tmi) delivery system for enhanced miRNA therapy.
  • To provide insights into the clinical translation of miRNA-based therapies for bone diseases.

Main Methods:

  • Investigated the impact of the miRNA network on four critical RCD programs in bone.
  • Developed and characterized a tetrahedral DNA nanostructure (TDN) for microRNA (miRNA) delivery (Tmi system).
  • Evaluated the potential of the Tmi system for protecting miRNAs and facilitating intracellular transport to regulate RCD pathways.

Main Results:

  • miRNA networks significantly influence the initiation and progression of apoptosis, autophagy, pyroptosis, and ferroptosis in bone.
  • The TDN-based Tmi system demonstrates excellent biocompatibility, cell penetration, and stability for miRNA delivery.
  • The Tmi system effectively releases miRNAs intracellularly to modulate RCD signaling pathways.

Conclusions:

  • miRNA targeting via the Tmi delivery system offers a promising strategy for treating bone diseases characterized by abnormal RCD.
  • The TDN platform provides a versatile and effective vector for miRNA nucleic acid drugs, overcoming limitations of current delivery methods.
  • This approach holds potential for advancing the clinical application of miRNA therapeutics in bone regenerative medicine and disease treatment.

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