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Effects of DNA Origami-Based Nanoagent Design on Apoptosis Induction in a Large 3D Cancer Spheroid Model
Johann M Weck1, Riya Nair1, Merve-Z Kesici1
1Max Planck Institute of Biochemistry, Martinsried and Center for NanoScience (CeNS), Ludwig-Maximilians-University, Am Klopferspitz 18, 82152, Munich, Germany.
Small (Weinheim an Der Bergstrasse, Germany)
|April 25, 2025
Summary
DNA origami nanoagents effectively target and eliminate cancer cells within 3D spheroids. Optimized designs based on size and FasL attachment strategy are crucial for successful nanotherapeutic development against solid tumors.
Area of Science:
- Nanotechnology
- Biotechnology
- Oncology
Background:
- DNA origami enables precise nanoscale control, valuable for nanotherapeutics.
- Fas receptor (FasR)/CD95-based nanoagents offer a promising strategy for cancer treatment via programmed cell death.
- Treating solid tumors with DNA origami therapeutics faces challenges in drug distribution and cellular behavior.
Purpose of the Study:
- Establish design principles for DNA origami nanoagents targeting solid tumors.
- Assess the penetration capabilities of DNA origami nanostructures in large cancer spheroids.
- Evaluate the efficacy of FasL-DNA origami nanoagents in inducing cancer cell apoptosis within 3D spheroids.
Main Methods:
- Investigated DNA origami nanostructure penetration in 3D cancer spheroids, correlating size and flexibility with efficacy.
- Developed and tested FasL-DNA origami nanoagents for their ability to induce apoptosis in cancer spheroids.
- Compared nanoagent performance in 3D spheroids versus traditional 2D studies.
Main Results:
- DNA origami penetration into spheroids was dependent on nanostructure size, not flexibility.
- Apoptosis induction was primarily governed by the FasL attachment strategy, surpassing structural influence.
- Optimized nanoagents halted spheroid growth and eradicated all cancer cells within the tested models.
Conclusions:
- Insights into critical design considerations for DNA-based therapeutics in complex cellular environments were provided.
- The study advances the development of DNA origami nanotherapeutics for solid tumor treatment.
- Optimized DNA origami nanoagents demonstrate significant potential for effective cancer therapy.

