## 1 Introduction  
Cancer has long been a leading cause of death worldwide. Accordingly, the Global Cancer Statistics indicates that female breast cancer has exceeded lung cancer to have the highest cancer incidence. Unfortunately, in recent years, there has been a gradual increase in the proportion of younger adults with breast cancer [1]. Although the major strategy for treating breast cancer involves surgery, the combinational therapy with chemotherapy, hormone therapy, or targeted therapy is still needed to prevent tumor recurrence [2]. However, these therapeutic methods have some limitations, such as various side effects, poor response, and drug resistance [3; 4; 5; 6]. Recently, drug delivery systems, such as polyethylene glycol-coated (pegylated) liposomes loaded with anticancer drugs, have been widely applied to overcome these limitations of cancer therapy [7; 8]. However, these liposomes still lack therapeutic efficacy. Thus, multifunctional liposomes have been developed to improve the therapeutic efficacy [9]. Tumor recurrence, metastasis, and drug resistance are the major limitations of the clinical therapy of breast cancer [10]. Mitochondria in cancer tissues are not only a power factory producing energy for growing cancer cells, but also play an important role in each stage of tumorigenesis. Moreover, mitochondrial DNA (mtDNA) is a key point to regulate metastasis and the response of anti-cancer drugs. Furthermore, the mitochondria in the stromal cells interfered with by cancer cells are critical to tumorigenesis, angiogenesis, and immunosuppression. The mitochondria enable cancer cells to migrate away from primary tumors and invade other organs to cause tumor metastasis and tumor recurrence. Moreover, cancer cells in a dormant state can regulate mitochondrial autophagy against the effect of anti-cancer drugs such as mitochondrial damages and the high levels of reactive oxygen species (ROS), promoting cancer cell survival [10; 11; 12; 13; 14]. Therefore, mitochondrial-targeting drug delivery for inducing mitochondrial dysfunction may be a potential therapeutic strategy for cancer. Designing a suitable mitochondrial-targeting drug delivery system can not only cause mitochondrial dysfunction that would eliminate the tumor, but also delivers nucleic acids to regulate mitochondrial gene expression for curing mitochondrial dysfunction in other diseases [15; 16]. Because of the TCA cycle metabolism and the electron transport chain, mitochondrial membrane potential shows highly negative charges compared to those of other organelles [17]. Therefore, several molecules, such as triphenylphosphonium (TPP), guanidine, and octaarginine-peptide [18; 19; 20], which possess positive charges, have been conjugated to drugs or nanoparticles for targeting the membrane of mitochondria via electrostatic interactions. However, the positive charges of drugs or nanoparticles easily interact with proteins in the blood circulation and then accumulate them in normal organs, causing unexpected side effects and reducing the therapeutic dosage of the drug in tumor tissues [21]. In this study, we synthesized a pH-sensitive charge-conversion copolymer, methoxy-poly(ethylene glycol)-block-poly(methacrylic acid-g-histidine) (mPEG-b-P(MAAc-g-His)-NH\({}_{2}\)), which possessed negative charges at neural pH (blood or cytoplasm) and absorbed protons from the imidazole rings of histidine to neutralize its negative charge at acidic pH (endosomes or secondary lysosomes). In addition, (3-carboxypropyl) triphenyl phosphonium (CTPP)-containing cationic liposomes were prepared to encapsulate an anticancer drug, ceramide. Ceramide is a neutral sphingolipid, which can regulate mitochondrial function and induce cell apoptosis [22; 23].