Exploring nonviral nanocarriers as RNA delivery platforms for breast cancer treatment

Breast cancer is a highly heterogeneous malignancy that requires increasingly precise and individualized therapeutic strategies. RNA-based therapeutics, including small interfering RNA (siRNA), microRNA (miRNA), messenger RNA (mRNA), and CRISPR-associated systems, enable precise regulation of tumour-associated genes, thereby offering targeted treatment with enhanced efficacy and reduced off-target toxicity. However, their clinical translation is hindered by poor stability, rapid degradation, and limited in vivo delivery efficiency. To address these limitations nonviral nanocarriers have emerged as promising platforms because of their structural tunability, low immunogenicity, and high transfection efficiency. Herein, we systematically summarize recent advances in nonviral nanocarriers for RNA delivery in breast cancer treatment, covering major carrier classes, including polymer-based, lipid-based, inorganic, and hybrid systems. A comparative framework based on cargo loading strategies is established to evaluate these nanocarriers in terms of targeting mechanisms, endosomal escape efficiency, therapeutic performance, and translational barriers. Furthermore, we discuss how tumour heterogeneity and subtype-specific characteristics inform the rational design of RNA delivery systems within a precision medicine context. This review provides a structured understanding of nonviral nanocarrier design principles and offers guidance for the development of next-generation RNA delivery platforms for breast cancer therapy. Breast cancer nanotherapeutics. Created in BioRender. Yu, Z. (2026) https://BioRender.com/ryig6u9 . • Nonviral nanocarriers enable precise and efficient RNA delivery for breast cancer. • Systematic comparison of organic, inorganic and hybrid RNA delivery platforms • Novel nanocarriers enhance RNA stability, tumour accumulation, and anticancer efficacy. • Nanoplatforms support gene silencing, immune modulation, and combination therapy. • Provides a strategic framework for personalized RNA-targeted breast cancer therapy