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Membrane bionic supramolecular nanomaterials for co-delivered of ribociclib and PEG10 siRNA for targeted therapy in

Yifan Yu1, Lidan Liu2, Ying Cai3

  • 1Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.

Cancer Letters
|July 15, 2026
PubMed

Insights

A novel nanodrug, RB/siPEG10@PMSNs-CM, co-delivers ribociclib and PEG10 siRNA to overcome breast cancer resistance. This biomimetic system shows anti-tumor and anti-metastatic effects with reduced toxicity, offering a promising immunotherapy strategy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Resistance to cyclin-dependent kinase (CDK) 4/6 inhibitors like ribociclib (RB) is a major limitation in breast cancer treatment.
  • PEG10 siRNA (siPEG10) can counteract this resistance, but targeted co-delivery to modify the tumor microenvironment is challenging.

Purpose of the Study:

  • To develop a biomimetic nanodelivery system for the synchronized co-delivery of RB and siPEG10.
  • To evaluate the therapeutic efficacy, immunotherapeutic potential, and underlying mechanisms of the developed nanodrug in breast cancer models.

Main Methods:

  • Synthesis of RB and siPEG10 loaded into PEG-β-CD-modified mesoporous silica nanoparticles (PMSNs) and coated with breast cancer cell membranes (RB/siPEG10@PMSNs-CM).
  • Characterization of nanomaterials for size, charge, drug loading, and pH-responsive release.
  • In vitro and in vivo evaluation of therapeutic efficacy, anoikis resistance, and toxicity in breast cancer models.

Main Results:

  • The RB/siPEG10@PMSNs-CM nanodrug demonstrated enhanced cellular uptake, pH-dependent release, and significant inhibition of tumor growth, migration, invasion, and metastasis.
  • The nanodrug effectively overcame anoikis resistance, induced apoptosis, reversed epithelial-mesenchymal transition (EMT) markers, and suppressed p-STAT3 and p-ERK signaling.
  • Reduced toxicity to liver and kidney tissues was observed compared to RB alone.

Conclusions:

  • The developed biomimetic nanodelivery system RB/siPEG10@PMSNs-CM successfully co-delivers RB and siPEG10, exhibiting anti-primary tumor and anti-metastatic efficacy.
  • The nanodrug overcomes anoikis resistance in breast cancer by suppressing MEK/ERK and STAT3 signaling pathways.
  • This platform offers a promising, safe combination strategy for advanced breast cancer immunotherapy and targeted treatment.
Keywords:
CyclodextrinNanocompositePEG10Ribociclib

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