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Calixarene-Embedded Nanoparticles for Interference-Free Gene-Drug Combination Cancer Therapy

Qi Liu1, Tian-Xing Zhang2, Yadan Zheng1

  • 1Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, College of Chemistry, Nankai University, National Demonstration Center for Experimental Chemistry Education, Nankai University, Tianjin, 300071, China.

Small (Weinheim an Der Bergstrasse, Germany)
|February 1, 2021
PubMed

Insights

This study introduces calixarene-embedded nanoparticles (CENPs) for effective cancer therapy. CENPs co-deliver drugs and genes, overcoming antagonism for improved anti-tumor effects in mice.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Combination therapy using molecular drugs and therapeutic genes is a promising strategy for malignant tumor treatment.
  • A significant challenge is the antagonism between therapeutic genes and molecular drugs, limiting effective combination therapies.
  • Developing systems to co-deliver genes and drugs without interference is crucial for advancing cancer treatment.

Purpose of the Study:

  • To develop a novel nanoparticle system for interference-free co-delivery of molecular drugs and therapeutic genes.
  • To create a versatile platform for combination cancer therapy using calixarene-embedded nanoparticles (CENPs).
  • To demonstrate the enhanced anti-tumor efficacy of the developed system in a preclinical model.

Main Methods:

  • Fabrication of calixarene-embedded nanoparticles (CENPs) with a cationic polyplex core and an acid-responsive polymer shell.
  • Incorporation of carboxylated azocalix[4]arene for hypoxia-responsive drug loading and gene-drug interference inhibition.
  • Co-delivery of doxorubicin (molecular drug) and a CRISPR interference system targeting miR-21 (therapeutic gene) using CENPs.
  • Evaluation of anti-tumor effects in a mouse model.

Main Results:

  • CENPs demonstrated improved circulation stability and enhanced tumor accumulation for gene delivery.
  • The hypoxia-responsive calixarene component effectively loaded molecular drugs and prevented drug-gene interference.
  • Combination therapy using doxorubicin and the miR-21 CRISPR system via CENPs showed significantly enhanced anti-tumor effects in mice.
  • The CENP system proved adaptable for various drug and gene combinations.

Conclusions:

  • Calixarene-embedded nanoparticles (CENPs) offer a universal platform for interference-free gene-drug combination cancer therapy.
  • This nanotechnology approach overcomes the limitations of antagonistic interactions between therapeutic genes and molecular drugs.
  • CENPs hold significant potential for developing next-generation combination cancer treatments.
Keywords:
CRISPRi systemcalixarene-embedded nanoparticlecombination therapydrug antagonismhost-guest complexation

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