Developing the Strategy to Use Silk Spheres for Efficient, Targeted Delivery of Oligonucleotide Therapeutics to Cancer Cells

 If we had ANY FUNCTIONING BRAIN CELLS in our stroke medical 'professionals' this would be looked at as a way to deliver drugs to the brain to increase neurogenesis, dendritic branching and axon pathfinding. But there are NO BRAINS AT ALL IN STROKE!

To prove total incompetence in stroke, nothing was done with this:

Making neurons from stem cells: Molecular mechanisms and spider silk substrates November 2013

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? Your patients need an explanation of why you aren't trying to get survivors recovered.

Why isn't your 'professional' solving stroke?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

Developing the Strategy to Use Silk Spheres for Efficient, Targeted Delivery of Oligonucleotide Therapeutics to Cancer Cells

Authors Molenda S, Deptuch T , Sikorska A, Lorenc P, Smialek MJ, Florczak-Substyk A , Pawlak P, Dams-Kozlowska H 

Received 28 January 2025

Accepted for publication 16 May 2025

Published 23 June 2025 Volume 2025:20 Pages 8023—8039

DOI https://doi.org/10.2147/IJN.S519906

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Professor Lijie Grace Zhang

Download Article [PDF] 

Sara Molenda,^{1– 3} Tomasz Deptuch,^1,2 Agata Sikorska,^1,2 Patryk Lorenc,^{1– 3} Maciej Jerzy Smialek,^1,2,* Anna Florczak-Substyk,^1,2 Piotr Pawlak,⁴ Hanna Dams-Kozlowska<sup>1,2

1</sup>Department of Cancer Immunology, Poznan University of Medical Sciences, Poznan, Poland; ²Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland; ³Doctoral School, Poznan University of Medical Sciences, Poznan, Poland; ⁴Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland

*Current address: Biozentrum, University of Basel, Basel, Switzerland, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

Correspondence: Hanna Dams-Kozlowska, Department of Cancer Immunology, Poznan University of Medical Sciences, 15 Garbary St, Poznan, 61-866, Poland, Email hdamskozlowska@ump.edu.pl

Introduction: Oligonucleotide-based drugs, such as siRNA, hold great promise for disease treatment, including cancer. However, their clinical application has challenges related to cell-specific delivery and susceptibility to degradation. The use of drug delivery systems (DDS) may address these problems. Nanoparticles of bioengineered spider silk demonstrate significant potential as DDS due to their biocompatibility and biodegradability. Another advantage of this material is the possibility of functionalization, which allows the control of its property. The main objective of this study was to develop a strategy for targeted delivery of oligonucleotide-based therapeutics into cancer cells using bioengineered silk technology.
Materials and Methods: Two spider silk spheres that bind oligonucleotides and target cancer cells that overexpress HER2 (HER2+) were constructed. One type of sphere was made of a newly designed silk, H2.1MS1KN, which contained two functional peptides: H2.1 for binding HER2 and KN for binding oligonucleotide. The second type of sphere was formed of a blend of two previously described proteins, H2.1MS1 and MS2KN; these proteins differed not only in the functional domain (H2.1 vs KN) but also in the sequence of silk (MS1 vs MS2). The ability of proteins to bind oligonucleotides was analyzed via gel electrophoresis. The biophysicochemical properties of particles were analyzed using an SEM, NanoSight, ZetaSizer, flow cytometry, and scanning confocal microscopy. The silk particle potential was analyzed using siRNA for silencing STAT3 expression in the HER2+ breast cancer model.
Results: Both H2.1MS1KN and H2.1MS1:MS2KN proteins efficiently bound nucleic acid. H2.1MS1:MS2KN formed smaller spheres than H2.1MS1KN. Although both H2.1MS1KN and blended H2.1MS1:MS2KN spheres were effectively loaded with oligonucleotides, only H2.1MS1:MS2KN spheres delivered siRNA to HER2+ cancer cells that successfully silenced STAT3 expression.
Conclusion: Not only the selection of functional peptides but also their quantity and type of silk is crucial when developing an effective silk-based DDS for delivering active siRNA.