Green synthesis nanoparticles for cancer immunotherapy: current applications and future perspectives

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Green-synthesized nanoparticles (GSNPs) represent a developing paradigm in cancer immunotherapy, integrating principles of nanotechnology and bio-derived materials. These nanoparticles, produced via eco-friendly biological reductants from plants, microorganisms, or natural polymers, constitute a sustainable class of bioactive biomaterials that can directly interface with immune cells and tissues. Beyond their environmentally conscious synthesis, GSNPs often retain biofunctional moieties from natural sources, providing intrinsic antitumoral and immunomodulatory properties. Such dual behavior enables them to act simultaneously as cytotoxic and immune-activating biomaterials. Relevant literature was identified through searches of PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2010 and 2026 using keywords related to green-synthesized nanoparticles, cancer immunotherapy, immune modulation, and the tumor immune microenvironment. This review comprehensively discusses the synthesis principles of GSNPs, their plant-, microbial-, and biopolymer-mediated fabrication routes, and their immune-modulating and tumoricidal mechanisms of relevance to biomaterial–cell interactions. GSNPs possess tunable physicochemical and biological characteristics that allow activation of macrophages, Th1 polarization, cytokine release, and attenuation of tumor-driven immune suppression. Furthermore, they act synergistically with checkpoint inhibitors or as nanovaccine platforms for antigen delivery. Through apoptosis induction, photothermal ablation, metabolic starvation, and modulation of NF-κB or PI3K/Akt signaling, GSNPs exert direct tumor-killing effects while maintaining biocompatibility. Cancer treatments that help the immune system fight tumors have improved outcomes for many patients. However, these therapies do not work for everyone, and some cancers develop ways to avoid immune attack. Researchers are therefore exploring new approaches that can improve immune responses against cancer while reducing side effects. One promising strategy involves the use of nanoparticles, which are extremely small materials that can carry medicines or interact with immune cells. In recent years, scientists have developed “green-synthesized nanoparticles,” which are nanoparticles produced using natural materials such as plant extracts, microorganisms, or natural polymers instead of harsh chemicals. These environmentally friendly nanoparticles may be safer and can sometimes provide additional biological benefits because they retain naturally occurring bioactive compounds. This review summarizes current research on the use of green-synthesized nanoparticles in cancer immunotherapy. Studies have shown that these nanoparticles can help activate immune cells, improve the delivery of cancer treatments, enhance the effectiveness of immune checkpoint inhibitors, and support the development of cancer vaccines. Some green-synthesized nanoparticles can also directly kill cancer cells while simultaneously stimulating immune responses. Although the results from laboratory and animal studies are encouraging, most green-synthesized nanoparticle systems have not yet reached clinical use. Important challenges remain, including large-scale manufacturing, quality control, safety evaluation, and regulatory approval. Further research is needed to determine how these technologies can be translated into safe and effective treatments for patients. Overall, green-synthesized nanoparticles represent a promising and sustainable approach that may contribute to the next generation of cancer immunotherapies.