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Related Concept Videos

Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Folate-Functionalization Enhances Cytotoxicity of Multivalent DNA Nanocages on Triple-Negative Breast Cancer Cells.

Valeria Unida1, Giulia Vindigni1, Sofia Raniolo1

  • 1Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

Pharmaceutics
|December 23, 2022
PubMed
Summary

DNA nanocages functionalized with folate show enhanced tumor cell targeting and miR-21 silencing compared to AS1411. Folate-mediated delivery improves intracellular stability and drug delivery, overcoming doxorubicin resistance in breast cancer.

Keywords:
AS1411DNA nanostructuredoxorubicin deliveryfolate receptormiR-21nucleolin

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Area of Science:

  • Biomedical Nanotechnology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • DNA nanotechnology enables programmable self-assembly of nanostructures for biomedical use.
  • Targeted delivery of therapeutic agents to cancer cells is crucial for efficacy and reducing side effects.
  • Drug resistance in cancer, particularly triple-negative breast cancer, remains a significant clinical challenge.

Purpose of the Study:

  • To develop and compare folate- and AS1411-functionalized DNA nanocages for cancer therapy.
  • To evaluate the miRNA silencing efficacy and cytotoxic effects of these nanostructures.
  • To investigate the role of targeting ligands and cell entry pathways in nanocarrier performance.

Main Methods:

  • Synthesis of folate-functionalized (Fol-NC), AS1411-linked (Apt-NC), and dual-functionalized (Fol-Apt-NC) DNA nanocages.
  • Analysis of miRNA (miR-21) silencing activity of nanostructures.
  • Assessment of doxorubicin-loaded nanocage cytotoxicity in drug-resistant triple-negative breast cancer cells (MDA-MB-231).
  • Comparison of cellular uptake and intracellular stability via folate-mediated versus nucleolin-mediated pathways.

Main Results:

  • Folate-functionalized nanocages demonstrated superior miR-21 silencing efficiency compared to AS1411-functionalized nanocages.
  • Dual-functionalized nanocages loaded with doxorubicin increased cytotoxicity by over 51% compared to free doxorubicin.
  • Folate-mediated cellular entry resulted in over four times higher intracellular stability than nucleolin-mediated entry.
  • The study highlights the enhanced efficacy of folate-targeted nanocarriers in overcoming doxorubicin resistance.

Conclusions:

  • DNA nanocages offer a versatile platform for targeted cancer therapy.
  • Folate functionalization enhances nanocarrier efficiency for miRNA silencing and drug delivery in breast cancer.
  • The folate-mediated cellular uptake pathway provides superior intracellular stability and therapeutic outcomes compared to nucleolin-mediated pathways.