Next-generation miRNA therapeutics: from computational design to translational engineering

Area of Science:

• Polymer Science
• Cancer Biology
• Nanomedicine

Background:

• MicroRNAs (miRNAs) show therapeutic potential for metastatic cancers by modulating oncogenic pathways.
• Clinical translation is limited by miRNA instability, poor tumor specificity, off-target effects, and delivery challenges.

Purpose of the Study:

• To review advances in cationic polymer-based nanocomplexes for multiplexed delivery of tumor-suppressive miRNAs.
• To explore strategies for overcoming metastatic cascade steps and therapeutic resistance.

Main Methods:

• Analysis of recent research on cationic polymer-based nanocomplexes for miRNA delivery.
• Dissection of structural design, targeting strategies, and controlled release mechanisms for polymeric carriers.

Main Results:

• Nanocomplexes provide structural versatility and tunable properties for co-delivering multiple miRNAs.
• These systems can synergistically regulate epithelial-mesenchymal transition (EMT), invasion, immune evasion, and colonization.
• The concept of "intelligent, multi-targeted, and personalized" miRNA nanomedicine is proposed.

Conclusions:

• Cationic polymer nanocomplexes represent a viable strategy for multiplexed miRNA delivery in cancer therapy.
• Addressing translational barriers like immunogenicity, synthesis scalability, and regulatory frameworks is crucial.
• Rational design of next-generation miRNA delivery systems is essential for precision oncology.