‘Smart’ Nanoparticles Deliver mRNA Directly to Tumors in New Cancer Therapy | WIREDSkip to main contentTHE WIRED APP IS HEREDOWNLOAD NOW »MenuWIREDSECURITYPOLITICSTHE BIG STORYBUSINESSSCIENCECULTUREREVIEWSMenuWIREDAccountAccountNewslettersSecurityPoliticsThe Big StoryBusinessScienceCultureReviewsChevronMoreExpandThe Big InterviewMagazineEventsWIRED InsiderWIRED ConsultingNewslettersPodcastsVideoLivestreamsWIRED StoreSearchSearchJavier CarbajalScienceSep 16, 2026 4:30 AM‘Smart’ Nanoparticles Deliver mRNA Directly to Tumors in New Cancer TherapyThe treatment can reprogram immune cells that have been corrupted by the cancer, strengthening the body’s ability to attack.Photograph: SCIEPRO/SCIENCE PHOTO LIBRARY/Getty ImagesCommentLoaderSave StorySave this storyCommentLoaderSave StorySave this storyOur immune systems don’t just fight bacteria and viruses invading the body. They are responsible for keeping our own tissues in check, taking out cancerous cells before they have a chance to grow. Once a tumor forms, however, it can create an environment that declaws cancer-fighting immune cells—in some cases even reprogramming them to suppress other parts of the immune system.Overcoming the oppressive tumor environment remains a barrier for even some of the most promising treatments. “One of the biggest challenges in cancer immunotherapy is that the immune system may be capable of attacking a tumor, but the tumor environment can stop those immune cells from doing their job,” University of Adelaide professor Chunxia Zhao explained in a press release.In a study published this week in Science Advances, Zhao’s team developed a system that can precisely deliver an mRNA therapy to transform immune cells back into allies. The researchers focused on tumor-associated macrophages, which—when rewired by signals from the cancer—hinder the arrival and activity of T cells, one of the body’s main weapons against cancer. The mRNA carries the instructions for producing CXCL9, a chemical signal for recruiting T cells.Flipping this switch is the easy part. mRNA technologies have been rapidly advancing, especially in the realm of cancer treatments, since they were first introduced to the public as Covid vaccines. However, you don’t want an immune-activating signal going just anywhere in the body. A risk of any immunotherapy is amping up the immune system too much, which can cause dangerous and potentially deadly side effects.To make sure the mRNA made it directly to the site of the tumor and nowhere else, the researchers developed a delivery method they dubbed “smart” nanoparticles. In any mRNA therapy, including a standard Covid shot, the mRNA is encased in some kind of nanoparticle, usually a lipid envelope. This fatty structure helps the molecules enter cells. In this case, the researchers took this basic technology and added a targeting mechanism to ensure the mRNA only got into the right cells.The smart nanoparticles were studded with antibodies that bind to TREM2, a protein present on the surface of tumor-associated immunosuppressive macrophages. A tumor’s environment tends to be a messy place full of many different cell types, so not only does this honing mechanism help get the therapy to the right part of the body, but only into macrophages in that region that need reprogramming.In addition to the mRNA, the smart nanoparticles also carried a drug called resiquimod, which can stimulate certain immune pathways. Initial laboratory results showed that not the previously lethargic macrophages began producing CXCL9 as well as other markers of an active immune state, such as NOS2, expression of which increased by a factor of 89.5. Signals of a more immunosuppressive state also notably decreased.The researchers then administered the smart nanoparticles to mice with aggressive breast cancer. After three doses, tumor growth slowed. The concentration of CXCL9 was approximately four times higher than in the control group, and the researchers detected the presence of T-cell activity. The treatment also reduced the proportion of macrophages with immunosuppressive characteristics by 63 percent.Often, cancer treatments are combined to attack the tumor from different directions. The researchers tested their new therapy in combination with two types of immunotherapy already used called immune checkpoint inhibitors. The combination did not further reduce the tumor size, but it did generate important changes in the immune system. Different types of T cells increased within the tumors and nearby lymph nodes—a finding associated with the potential for a more lasting immune response.The researchers also did not detect any negative effects to other organs, but they urged caution that more studies are needed to evaluate the safety before human trials can begin.“This is an important proof of concept that we can use mRNA and nanoparticle technology to reprogram the immune environment of a tumor,” said Professor Zhao. “There is still significant work to do before this approach could be considered for patients, but these results provide an encouraging foundation for developing more targeted cancer immunotherapies.”This story originally appeared on WIRED en Español and has been translated from Spanish.CommentsBack to topJoin the discussionCommentsBack to topTriangleYou Might Also LikeIn your inbox: Maxwell Zeff's dispatch on the business of AIWhy normal people aren’t using AI agentsBig Story: How data centers broke American politicsHackers stalked me by hijacking a cheap pink plastic watchSpecial edition: The WIRED guide to expanding your mindJavier Carbajal is a contributor to WIRED en Español. He is a graduate of the University of Houston and studied at the SOGEM Writers School. He has written for publications including Noticieros Televisa/Nmas, Sopitas.com, LifeBoxset, and Erizos. He is passionate about literature, international politics, and the media, as well as ... 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The development of 'smart' nanoparticles represents a novel approach to cancer therapy by focusing on reprogramming the immune system within the tumor microenvironment. The fundamental challenge in cancer immunotherapy, as noted by Professor Chunxia Zhao, is that while the immune system may have the capacity to attack a tumor, the oppressive tumor environment often inhibits the necessary immune cells from functioning effectively to eliminate cancerous cells. This barrier necessitates methods to override the tumor's immunosuppressive signals to strengthen the body's natural anti-cancer defenses.

Zhao's team developed a system utilizing messenger RNA (mRNA) therapy, delivered via targeted nanoparticles, designed to transform corrupted immune cells back into allies. The research specifically targeted tumor-associated macrophages, which are critical in establishing the immunosuppressive environment that hinders the activity of T cells, the body's primary weapon against cancer. The mRNA payload was engineered to carry instructions for producing CXCL9, a crucial chemical signal required for recruiting T cells.

To ensure that this immune-activating signal was delivered precisely to the site of the tumor and avoided systemic immune activation, the researchers incorporated a targeting mechanism into their nanoparticle design. These smart nanoparticles were functionalized with antibodies that specifically bind to TREM2, a protein expressed on the surface of tumor-associated immunosuppressive macrophages. This targeting mechanism allows the therapy to selectively engage only those macrophages within the tumor region that require reprogramming.

In addition to the mRNA, the nanoparticles were loaded with resiquimod, a substance known to stimulate specific immune pathways. Laboratory results demonstrated that treating the previously lethargic macrophages induced them to begin producing CXCL9 and other markers of an active immune state, such as NOS2, which increased by a factor of 89.5. Concurrently, signals indicative of an immunosuppressive state notably decreased.

When these smart nanoparticles were administered to mice with aggressive breast cancer, the treatment yielded significant therapeutic effects. After three doses, the growth of the tumor slowed. The concentration of CXCL9 was observed to be approximately four times higher than in the untreated control group, and evidence of T-cell activity was detected within the tumor. Furthermore, the treatment effectively reduced the proportion of macrophages exhibiting immunosuppressive characteristics by sixty-three percent. The researchers also explored combining this mRNA-nanoparticle therapy with existing immunotherapies, specifically immune checkpoint inhibitors. While this combination did not result in further tumor size reduction, it successfully induced important shifts in the immune system, leading to an increase in different types of T cells within the tumors and nearby lymph nodes, suggesting potential for a more enduring immune response. Although no negative effects on other organs were detected, the researchers emphasized the necessity for further studies to fully evaluate safety before advancing human trials. This work provides a crucial proof of concept, demonstrating the viability of using mRNA and nanoparticle technology to effectively reprogram the immune environment surrounding a tumor.