Researchers are exploring the ability of gold nanoparticles (yellow dots) to transport medications into the body.(Image credit: Veronika Sapozhnikova, Konstantin Sokolov, Rebecca Richards-Kortum/M.D. Anderson Cancer Center and Rice University via NIH/Flickr)
When the earliest cells emerged on Earth roughly 3.8 billion years prior, viruses were already present to encounter them. Since that time, viruses have been formulating techniques to affect cells, and cells have been countering by developing methods to halt such contaminations. This ongoing development ultimately resulted in the formation of your immune response.
A fundamental part of your immune system is the skill to differentiate “self” from “nonself” so that it can eradicate and eliminate external elements from your system. Although this immune action shields you against viruses, it also bears on the functionality of foreign substances like medicines.
I’m a scientist investigating approaches to improve drug action, counting methods to direct them to the disease site within the body prior to removal or breakdown. An approach to achieve this involves encapsulating drugs inside nanoparticles — entities that are diminutive enough for cellular uptake. Despite the fact that these materials still incite an immune reaction to clear them from the system, experts such as myself have discovered this reaction might really be harnessed to boost the efficacy of cancer treatments.
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The immune response and drug transport
In addition to spotting pathogens, your immune system also reacts to tissue deterioration. This action may manifest as inflammation — such as redness and distension — when medications are introduced into the body via a needle.
Typically, this inflammatory response is limited. However, the likelihood of a persistent reaction is heightened when drugs are given gradually over an extended period, like during chemotherapy sessions that might last an hour or more. Consequently, some patients are administered anti-inflammatory drugs before the session to lower the potential for negative immune consequences during therapy.
The latest advancements in medication delivery into the body involve the employment of nanoparticles. These substances — which may consist of lipids, proteins, gold, or other components — offer the advantage of extreme minuteness: A typical nanoparticle’s diameter is about 10-thousandths of a millimeter. Their reduced size empowers diseased cells to uptake them readily. Hence, when nanoparticles bear drugs, they serve as a mechanism for drug transport.
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In spite of their small dimension, nanoparticles have the capacity to contain a significant quantity of drug molecules, enabling them to convey a robust treatment payload straight into a cell. They’re also capable of delivering drugs composed of DNA and RNA. The prime instance of such tech lies in the COVID-19 vaccine, which leans on nanoparticles constructed of altered fat molecules to administer mRNA, which educates the immune response in defending against COVID-19 infection.
Your intrinsic immune system also recognizes nanoparticles as foreign entities as they’re introduced into your system. As a result, a few patients undergo an initial inflammatory response as their body attempts to counter the nanoparticle.
However, suppose this reaction could, in fact, be leveraged to advance treatment?
Harnessing the innate immune response
For the last 30 years, my research facility at the University of Colorado has been studying nanoparticle-facilitated drug delivery. In recent times, we’ve pivoted toward comprehension of how the intrinsic immune system reacts to the injection of nanoparticles. Despite this immune action generally being seen as a disadvantage, we sought to determine if it might enhance therapy.
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A 2022 study detailing how nanoparticles have an effect on immune reactions in lab mice showed that the intrinsic immune reaction instigated by an initial dose of drug-transporting nanoparticles will diminish the effects of subsequent doses if injected soon after — generally within days. This works by expelling the drug from the system more expeditiously. Such a reaction parallels how an initial viral contamination triggers a swift protective response against following contamination from another pathogen.
Nanoparticles — the yellow spots — can be crafted to hone in on cancer cells, which are blue.
A crucial element of such a defensive influence entails the output of a protein termed interferon lambda. This molecule “interferes” with the contamination pathway by restricting viruses from infiltrating assorted tissues within the system. Experts have earlier evaluated this protein as a prospective antiviral drug to combat COVID-19.
Similarly, the interferon lambda manufactured in reply to the initial nanoparticle dosage curtails the ability of the subsequent dose to convey medication to healthy tissues throughout the system. Nonetheless, it didn’t impair the nanoparticle’s capacity to reach tumors, perhaps because tumors can impact the immune response.
Within conventional cancer treatment, chemotherapy agents destroy the tumor. Because these medications prove harmful to healthy cells as well, patients typically undergo side effects like hair thinning, digestive issues, and skin irritation. Leaning on nanoparticles for cancer treatment delivery could aid in mitigating these adverse effects, and fusing them with interferon lambda might enable nanoparticle-encapsulated medication to endure in the system long enough to execute its complete effect.
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Our collective is probing if directly administering interferon lambda prior to chemotherapy involving nanoparticles may limit the quantity of drug that ends up within healthy tissues, while elevating their concentration inside tumors. Within an initial evaluation of such a methodology performed on mice exhibiting colon cancer, all mice that received interferon lambda witnessed expanded survival duration and lessened weight decrement. An enhanced grasp of such an effect could aid experts in ultimately evaluating such an approach toward malignancy treatment on human participants.
Scientists have some distance to cover in devising nanoparticles that are as adept as pathogens in entering cells. Even so, our anticipation lies in harnessing an immune response that grew close to a billion years ago to avert viral contaminations, and that it could alleviate the detrimental side effects resulting from treatments, all while enhancing their potency.
This revised piece has been republished from The Conversation under a Creative Commons license. Consult the original article.
Tom AnchordoquyProfessor of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus
Tom Anchordoquy serves as a professor within the University of Colorado School of Pharmacy, where he has been part of the faculty lineup since 1998. His investigations concentrate on the blueprinting of nanomedicines, spanning lipid-DNA composites and exosome-centered drug transportation frameworks, as well as methodologies leveraging nanoparticle-induced immune reactions to refine cancer therapies. His laboratory also undertakes formulation studies using diminutive molecules to address a spectrum of ailments.
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