Degradable Hyaluronic Acid/Protamine Sulfate Interpolyelectrolyte Complexes as miRNA‐Delivery Nanocapsules for Triple‐Negative Breast Cancer Therapy

Metastatic relapse is a leading cause of cancer‐associated death and one of the major obstacles for effective therapy against triple‐negative breast cancer. To address this problem, a miRNA‐delivering nanocapsule technology based on hyaluronic acid (HA)/protamine sulfate (PS) interpolyelectrolyte complexes (HP‐IPECs) is developed for efficient encapsulation and intracellular delivery microRNA‐34a (miR‐34a), which is a potent endogenous tumor suppressor of breast cancer. The nanocapsules are successfully generated through a self‐assembly approach mediated by an electrostatic interaction. In vitro and in vivo experiments illustrate that miR‐34a can be efficiently encapsulated into HP‐IPECs and delivered into breast cancer cells or breast cancer tissues. Nanocomplex‐assisted delivery of miR‐34a induces cell apoptosis and suppresses migration, proliferation, and tumor growth of breast cancer cells via targeting CD44 and a Notch‐1‐signaling pathway. The obtained results suggest that HP‐IPECs have a great potential as a biodegradable vector for microRNA‐based therapy against triple‐negative breast cancer.