<p>Breast cancer (BC) remains leading cause of cancer related deaths in women, while the traditional BC therapies are usually constrained by resistance to the drugs, recurrence and systemic toxicity. RNA interference (RNAi) is an emerging approach that silence oncogenes with high specificity and regulate tumor-promoting pathways. Although RNAi is a promising approach, its clinical use is limited due to rapid degradation, poor cellular uptake and immune activation. Green nanomaterials (GNMs), derived from biodegradable polymers, natural biomolecules, and plant-extracts have shown potentials to overcome these obstacles due to their sustainability and biocompatibility.&#xa0;Biopolymers such as chitosan, alginate, and polylactic acid can be designed to shield RNA molecules and release them in response to pH changes or enzymatic activity. Similarly, biomolecule-based carriers, including silk fibroin, collagen, and dextran, provide structural stability to RNA molecules. Plants based metallic nanoparticles (NPs), such as gold, silver, and zinc oxide NPs possess distinctive characteristics that enhance targeted drug delivery and treatment outcomes. Preclinical research has shown promising results such as deep tumor shrinkage in triple-negative breast cancer and prevented metastasis when RNAi is combined with plant compounds and plant-based NPs.&#xa0;Nevertheless, large scale production, stability, purity and NPs related immunity issues are still unsolved. Future efforts are expected to focus on smart, stimuli-responsive and bio-nano hybrid designs guided by computer models to enhance precision and accelerate clinical translation. Together, green nanotechnology and RNAi therapies offer a safer, more effective, and eco-friendly approach for personalized breast cancer treatment.</p><p><b>Lay summary:</b> Researchers are developing a precise and less toxic method to fight breast cancer. An intelligent technology named RNA interference (RNAi) silence the targeted genes that cause cancer. Some RNAi-based therapies have already been approved by the FDA, proving their clinical effectiveness. However, a key challenge is how to deliver RNAi safely to cancer cells without causing harmful side effects from the carrier materials.</p><p>A promising solution is to combine RNAi with tiny, eco-friendly nanoparticles made from natural materials such as plants or algae. These natural particles are used as protective taxis, transporting the treatment directly to the tumor. This innovative approach represents a major step toward gentle, personalized cancer therapy by combining precise gene silencing with sustainable and biocompatible nanocarriers.</p> Graphical Abstract <p></p>