Biotechnologie
Sferische Nucleïnezuren Verbeteren Chemotherapieafgifte Dramatisch
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Nanotechnologie‑gedreven therapeutische afgifte bij kanker
Our understanding of cancer has greatly progressed over the last few decades, leading to the discovery of various molecules able to kill cancer cells. The problem is, however, that cancer cells are still part of the body, even if they act abnormally and will ultimately kill the rest of the cells.
Dit betekent dat dezelfde geneesmiddelen die kankercellen doden, ook behoorlijk toxisch kunnen zijn voor de overige cellen van het lichaam. Bovendien belemmeren de metabole en genetische afwijkingen van kankercellen vaak hun opname van de chemische stoffen die tegen hen effectief zijn.
Om beide redenen kan het proces van het afleveren van kankermedicijnen aan kankercellen net zo belangrijk, zo niet belangrijker, zijn dan de werkzaamheid van het medicijn zelf. Op deze manier worden niet alleen negatieve bijwerkingen verminderd, maar is de behandeling efficiënt genoeg om de patiënt te redden.
Precieze targeting is ook belangrijk om het risico op terugkeer van kanker te verkleinen, aangezien een hogere efficiëntie minder kans geeft op “verborgen” residuele kankercellen.
Een bijzonder veelbelovende afleveringsmethode maakt gebruik van Sferische Nucleïnezuren (SNAs), een nieuw type nanomolecuul dat goed wordt verdragen door het lichaam. Onderzoekers van Northwestern University hebben onlangs aangetoond dat SNAs de efficiëntie van een leukemiegeneesmiddel radicaal kunnen verhogen.
They published their results in ACS Nano1, under the title “Chemotherapeutic Spherical Nucleic Acids”.
Uitdagingen bij de afgifte van kankermedicijnen
A lot of the increase in survival rate from cancer in the past 2 decades has been linked to better delivery systems for cancer treatments. For example, antibodies, especially monoclonal antibodies, have risen to become one of the best therapeutic options for many cancer types.
Een andere optie is het gebruik van een passief richtingssysteem, waarbij biomoleculen of nanodeeltjes specifiek op de kankercellen mikken.
Bron: MDPI
Terwijl antilichamen de afgelopen jaren in de schijnwerpers van de oncologie stonden, is een opkomend alternatief nanotechnologie, met speciaal ontworpen nanodeeltjes die direct aan kankercellen kunnen hechten en chemotherapie voorbij het celmembraan kunnen afleveren.
Bron: MDPI
Sferische Nucleïnezuren (SNAs)
The researchers in this study used liposomal spherical nucleic acid (SNA) constructs. They are built of a nanoparticle core, surrounded by a shell made of a densely packed, highly oriented arrangement of nucleic acids.
Bron: Nature
SNAs werden voor het eerst gecreëerd in 1996 door Chad Mirkin aan Northwestern University, die tevens de hoofdonderzoeker van deze studie is.
Veel verschillende SNAs kunnen worden gemaakt door de aard van de nanodeeltje‑kern (goud, zilver, silica, liposoom, eiwitten, enz.) en de sequenties van de nucleïnezuren (DNA, RNA, enz.) te variëren.
Bron: Cancers
Structurele nanomedicijnen: Een nieuw tijdperk in medicijnafgifte
In previous studies, it was discovered that cells recognize SNAs and invite them inside. More importantly, cancer cells, due to their excessive activity, are incorporating SNAs at a much higher rate than healthy cells.
So the very nature of cancer cells makes them more reactive to SNAs.
“De meeste cellen hebben scavenger‑receptoren op hun oppervlak. Maar myeloïde cellen overexpressen deze receptoren, waardoor er nog meer van zijn.
Als ze een molecuul herkennen, trekken ze het de cel in. In plaats van zich te moeten forceren om de cel binnen te dringen, worden SNAs natuurlijk opgenomen via deze receptoren.”
This is part of the overall growing field of structural nanomedicine, which uses precise structural, as well as compositional, control to fine-tune how nanomedicines interact with the human body.
There are 7 SNA-based therapies currently in clinical trials, not only for cancer, but also for infectious diseases, neurodegenerative diseases, and autoimmune diseases.
Pre‑klinische resultaten bij acute myeloïde leukemie (AML)
Opbouw van chemotherapie‑SNAs
The researchers tested their liposomal SNA for the treatment of leukemia. They used 5-fluorouracil (5-Fu), with the nucleic acid component of the SNA made of 10 units of chemically interconnected 5-fluoro-2′-deoxyuridine
Bron: ACS Publications
De traditionele chemotherapie 5‑Fu bereikt kankercellen vaak niet efficiënt. Het kan bovendien veel problematische bijwerkingen veroorzaken: misselijkheid, vermoeidheid en, in zeldzame gevallen, zelfs hartfalen.
The problem is not only the toxicity of the drug itself, but that barely 1% of the treatment dissolves in the body. So it clumps or retains a solid form, and the body cannot absorb it efficiently.
We all know that chemotherapy is often horribly toxic. But a lot of people don’t realize it’s also often poorly soluble, so we have to find ways to transform it into water-soluble forms and deliver it effectively.”
The over-expression of SNA receptors by myeloid cells (which are causing leukemia) means that even a lower dose of 5-Fu will still reach the cancer cells, but a much lower dose reaches healthy cells.
An extra bonus is that the liposome SNAs are very soluble, removing that problem as well.
“Today’s chemotherapeutics kill everything they encounter. So, they kill the cancer cells, but also a lot of healthy cells. Our structural nanomedicine preferentially seeks out the myeloid cells.
Instead of overwhelming the whole body with chemotherapy, it delivers a higher, more focused dose exactly where it’s needed.”
Efficacy Gains with SNA Delivery
The SNA-driven delivery of 5-Fu to inside cells is 12.5x higher than without the SNA. More importantly, in an in-vitro study, a 4 orders of magnitude (>1,000x).
In mice used to simulate human leukemia, the chemotherapeutic SNA had a 59x higher antitumor efficacy than 5-Fu alone. Maybe even more importantly, the mice did not display any of the side effects of 5-Fu when treated with SNAs.
“In animal models, we demonstrated that we can stop tumors in their tracks.
If this translates to human patients, it’s a really exciting advance. It would mean more effective chemotherapy, better response rates and fewer side effects.”
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| Metriek | Vrije 5-Fu (standaard) | SNA-bezorgde 5-Fu (liposomale SNA) |
|---|---|---|
| Celopname (AML-cellen) | 1× (baseline) | ~12,5× hoger |
| In‑vitro celdodend vermogen | 1× (baseline) | Tot ~10.000× hoger |
| Antitumor effectiviteit in muizen (AML-model) | 1× (baseline) | ~59× grotere tumorreductie |
| Waargenomen toxiciteit/bijwerkingen (in studie) | Significante bekende bijwerkingen van 5-Fu (misselijkheid, vermoeidheid, cardiotoxiciteit) | Geen duidelijke toxiciteit waargenomen in beoordeelde parameters (muizenstudie) |
Toekomstige klinische en commerciële toepassingen van SNAs
SNAs are quickly becoming a very promising delivery mechanism for chemotherapy drugs.
The next step will likely be to look at other drugs on the same animal model, to see if the results can be improved even further. For example, another chemotherapy drug known for its toxicity problems but highly efficient at killing cells could be made tolerable or almost harmless with SNAs, while becoming even more able to kill cancer cells.
In the long run, human studies for evaluating the potential of this technology in real patients will need to be done. This is often a costly process, starting from phase I (testing healthy people to determine if they can tolerate the drug) to phase III (testing on many real cancer patients).
Commercialisation and SNA Start-ups
CancerVax
Chad A. Mirkin, the lead scientist of this study and discoverer of SNAs, is also the scientific founder of Flashpoint Therapeutics, a company dedicated to deploy SNAs into human therapeutical applications.
They claim from 9 in-vivo studies that SNAs show a 35x improved delivery, 80x stronger immune activation, and 6.5x increased tumor killing by T-cells. The SNAs can be absorbed by more than 60 different types of cells.
Bron: Flashpoint Therapeutics
The company has announced a research agreement with CancerVax, a company developing a universal cancer treatment platform that uses the body’s immune system to fight cancer.
Direct investment in CancerVax is only possible for accredited investors, but an equity fundraising through crowdfunding is also ongoing, open to all types of investors, at $2.1/share, putting the company at a valuation above $80M.
“CancerVax’s Universal Cancer Treatment platform requires precise, multi-component delivery to effectively detect and mark cancer cells.
Our technology is uniquely suited to this challenge, offering the ability to package and deliver Smart mRNA payloads with the efficiency and accuracy needed to realize the full potential of this promising therapeutic approach.”
Besides cancer, SNAs could also be used for delivery of CRISPR-based therapies.
LNP‑SNAs entered cells up to three times more effectively, caused less toxicity, boosted gene‑editing efficiency threefold, and improved precise DNA repairs by more than 60%, compared to standard lipid nanoparticle delivery systems.
Overall, SNAs are clearly reaching the point where they are a very promising technology from in‑vitro and in‑vivo animal studies, and are ready to explore human applications for cancer, gene therapy, and other key medical applications.
They are also likely going to benefit from the emergence of other precision therapies and technologies, like CRISPR, which will boost the potential of SNAs.
Bestudeerde Studie
1 .Taokun Luo, Young Jun Kim, Zhenyu Han, Jeongmin Hwang, Sneha Kumari, Vinzenz Mayer, Alex Cushing, Roger A. Romero, Chad A. Mirkin. Chemotherapeutic Spherical Nucleic Acids. ACS NanoVol 19/Issue 44. 29 oktober 2025. https://pubs.acs.org/doi/10.1021/acsnano.5c16609
