Advances with Lipid-Based Nanosystems for siRNA Delivery to Breast Cancers

Abstract

Breast cancer is the most frequently diagnosed cancer among women. Breast cancer is also the key reason for worldwide cancer-related deaths among women. The application of small interfering RNA (siRNA)-based drugs to combat breast cancer requires effective gene silencing in tumor cells. To overcome the challenges of drug delivery to tumors, various nanosystems for siRNA delivery, including lipid-based nanoparticles that protect siRNA from degradation for delivery to cancer cells have been developed. These nanosystems have shown great potential for efficient and targeted siRNA delivery to breast cancer cells. Lipid-based nanosystems remain promising as siRNA drug delivery carriers for effective and safe cancer therapy including breast cancer. Lipid nanoparticles (LNPs) encapsulating siRNA enable efficient and specific silencing of oncogenes in breast tumors. This review discusses a variety of lipid-based nanosystems including cationic lipids, sterols, phospholipids, PEG-lipid conjugates, ionizable liposomes, exosomes for effective siRNA drug delivery to breast tumors, and the clinical translation of lipid-based siRNA nanosystems for solid tumors.

Keywords: breast cancer; gene silencing; lipid NPs; personalized therapy; siRNA delivery.

Figure 1

Classification of siRNAs used in breast cancer therapy [10].

Figure 2

Challenges in in vivo delivery of RNA therapeutics using nanoparticles. (A) Spontaneous hydrolysis of RNAs. (B) Nuclease-mediated degradation. (C) Protein adsorption. (D) Immune recognition and clearance. (E) Renal clearance. (F) Endothelial barrier. (G) Cell membrane barrier. (H) Endosomal barrier. (I) Insufficient cargo release. Adapted from [69] with copyright permissions.

Figure 3

Aptamer-conjugated liposome for immunogenic chemotherapy with reversal of immunosuppression. Adapted from [99] with copyright permissions.