Related Experiment Video
Updated: May 8, 2026
Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
Published on: September 27, 2013
Development of hybrid aptamers-engineered PROTACs for degrading VEGF165 in both tumor- and vascular endothelial cells
Ziting Feng1, Duoli Xie2, Fang Qiu2
1Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.
Abstract:
Tumors and angiogenesis are connected through a complex interplay. VEGF165, generated from both tumor and vascular endothelial cells, serves as a mutual benefit for both cell types. Therapeutic approaches modulating VEGF165 have been proposed as promising antitumor therapies. PROTACs are bifunctional molecules that exploit the intracellular ubiquitin-proteasome system to degrade specific proteins. To date, there are no targeted PROTACs designed to degrade VEGF165 in both tumor and vascular endothelial cells. The aptamer AS1411 is notable for its ability to selectively recognize and enter both tumor and vascular endothelial cells by targeting the cell surface nucleolin (NCL). Moreover, AS1411 has also been repurposed as an intracellular recruiter of E3 ligase MDM2 via leveraging NCL as a molecular bridge. In this study, we conjugated AS1411 with a VEGF165-specific aptamer V7t1, creating hybrid aptamers-engineered PROTACs. The PROTACs demonstrate remarkable selectivity for both tumor and vascular endothelial cells and facilitate the ubiquitination and proteasomal degradation of VEGF165. The PROTACs inhibit the growth of tumor cells and also impede angiogenesis, without causing toxicity to normal tissues. The hybrid aptamers-engineered PROTACs provide an avenue for disrupting the tumor-angiogenesis interplay through modulation of VEGF165 in both tumor and vascular endothelial cells.
Insights
Researchers developed novel PROTACs by conjugating aptamers to target and degrade VEGF165 in both tumor and vascular endothelial cells. This approach inhibits tumor growth and angiogenesis without harming normal tissues.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tumor growth and angiogenesis are closely linked, with VEGF165 playing a crucial role in supporting both tumor cells and vascular endothelial cells.
- Current therapeutic strategies targeting VEGF165 show promise but lack dual targeting of both cell types.
- Proteolysis-targeting chimeras (PROTACs) offer a novel mechanism for targeted protein degradation.
Purpose of the Study:
- To design and synthesize novel hybrid aptamer-engineered PROTACs capable of degrading VEGF165 in both tumor and vascular endothelial cells.
- To evaluate the efficacy of these PROTACs in inhibiting tumor growth and angiogenesis.
- To assess the safety profile of the developed PROTACs in normal tissues.
Main Methods:
- Conjugation of the AS1411 aptamer (targeting nucleolin) with the V7t1 aptamer (targeting VEGF165) to create hybrid aptamers.
- Utilizing AS1411 to recruit E3 ligase MDM2 for targeted ubiquitination and proteasomal degradation of VEGF165.
- Assessing PROTAC selectivity, VEGF165 degradation, tumor growth inhibition, and anti-angiogenic effects in vitro and in vivo models.
Main Results:
- The hybrid aptamer-PROTACs exhibited high selectivity for both tumor and vascular endothelial cells.
- Successful ubiquitination and proteasomal degradation of VEGF165 were observed.
- Significant inhibition of tumor cell proliferation and angiogenesis was achieved.
- No observable toxicity in normal tissues was reported.
Conclusions:
- Hybrid aptamer-engineered PROTACs effectively degrade VEGF165 in both tumor and vascular endothelial cells, disrupting the tumor-angiogenesis axis.
- This novel therapeutic strategy shows potential for effective cancer treatment with improved safety.
- The developed PROTACs offer a promising new avenue for modulating VEGF165 in both tumor and endothelial cells.
