Related Experiment Video

Updated: Sep 30, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

7.7K

Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system

Nako Maishi1,2,3, Yu Sakurai4,5, Hiroto Hatakeyama4,6

  • 1Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan.

Cancer Science
|March 10, 2022
PubMed

Insights

Targeting biglycan in tumor endothelial cells (TECs) inhibits renal cell carcinoma growth. This study used a novel nanodevice (MEND) to deliver siRNA, reducing biglycan and normalizing the tumor microenvironment.

Area of Science:

  • Oncology
  • Nanomedicine
  • Molecular Biology

Background:

  • Tumor blood vessels and tumor endothelial cells (TECs) are crucial for tumor progression and metastasis.
  • Biglycan, a proteoglycan highly expressed in TECs, promotes TEC migration, angiogenesis, and tumor cell metastasis.
  • Targeting TECs offers a therapeutic strategy for cancer treatment.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting biglycan in TECs for renal cell carcinoma (RCC).
  • To develop and evaluate a targeted delivery system for siRNA against biglycan in TECs.
  • To assess the impact of biglycan inhibition on tumor growth and the tumor microenvironment.

Main Methods:

  • Development of a multifunctional envelope-type nanodevice (MEND) incorporating cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) for targeted delivery to αVβ3 integrin-expressing TECs.
  • Encapsulation of siRNA targeting biglycan within the RGD-MEND system.
  • In vitro validation of MEND delivery and RNA interference (RNAi)-mediated gene silencing in OS-RC-2 derived TECs.
  • In vivo intravenous administration of RGD-MEND in OS-RC-2 tumor-bearing mice and assessment of MEND specificity, biglycan knockdown, and therapeutic effects.

Main Results:

  • RGD-MEND successfully delivered siRNA into TECs, achieving RNAi-mediated biglycan gene silencing both in vitro and in vivo.
  • Flow cytometry confirmed specific MEND delivery to TECs in tumor-bearing mice.
  • Quantitative RT-PCR demonstrated significant knockdown of biglycan expression.
  • Treatment with biglycan siRNA-containing MEND resulted in inhibition of tumor growth and normalization of tumor microenvironmental factors like fibrosis.

Conclusions:

  • Biglycan expressed in TECs is a viable therapeutic target for renal cell carcinoma.
  • The RGD-MEND system provides effective and specific delivery of siRNA to TECs for gene silencing.
  • Inhibition of biglycan in TECs holds promise for novel cancer treatment strategies by reducing tumor growth and improving the tumor microenvironment.
Keywords:
biglycandrug delivery systemtumor angiogenesistumor endothelial celltumor microenvironment

More Related Videos

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

16.8K
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats08:55

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats

Published on: April 15, 2016

9.6K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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.
There are several types of targeted therapies against...
7.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
702
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.0K