Aptamers are short non-coding, single-stranded oligonucleotides (RNA or DNA) developed through Systematic Evolution of Ligands by Exponential enrichment (SELEX) in vitro. Similar to antibodies, aptamers can bind to specific targets with high affinity, and are considered promising therapeutic agents as they have several advantages over antibodies, including high specificity, stability, and non-immunogenicity. Furthermore, aptamers can be produced at a low cost and easily modified, and are, therefore, called “chemical antibodies”. In the past years, a variety of aptamers specifically bound to both breast cancer biomarkers and cells had been selected. Besides, taking advantage of nanomaterials, there were a number of aptamer-nanomaterial conjugates been developed and widely investigated for diagnostics and targeted therapy of breast cancer. In this short review, we first present a systematical review of various aptamer selection methods. Then, various aptamer-based diagnostic and therapeutic strategies of breast cancer were provided. Finally, the current problems, challenges, and future perspectives in the field were thoroughly discussed.

Developing multifunctional nanomaterials with chemodynamic therapy (CDT)-based combination therapy has increasingly become a promising strategy for cancer treatment. Herein, a metal–phenolic network-based multifunctional nanocomposite (PID@Fe–TA) via the noncovalent interaction of multiple nontoxic raw materials has been designed to integrate the synergistic effect of CDT, photothermal therapy (PTT) and chemotherapy into one nanoplatform for breast cancer treatment. Benefiting from the pH-responsive properties and the assistance of near infrared (NIR) laser irradiation, the outer shell Fe³⁺–tannic acid (TA) complexes of PID@Fe–TA can be easily degraded into Fe³⁺ and TA as well as to release chemotherapeutic drugs (doxorubicin, DOX) and photothermal transforming agents (indocyanine green, ICG) in a tumor microenvironment (TME) or cancer cells. The released TA can accelerate the reduction of Fe³⁺ to Fe²⁺ for ensuring effective conversion of hydrogen peroxide (H₂O₂) into a highly toxic hydroxyl radical (˙OH) via the Fenton reaction. The exposed DOX can enter the cell nucleus to induce chemotherapy. The released ICG can locate the distribution of nanocomposites in the body. Besides, the heat generated from PID@Fe–TA after NIR laser irradiation can further promote the therapeutic effect of PPT-enhanced CDT. Importantly, an excellent therapeutic efficacy is achieved both in in vitro and in vivo via the CDT/PTT/chemotherapy combination based on this “all-in-one” nanoplatform, providing a good paradigm for effective cancer eradication.

Aptamers are single-stranded DNA or RNA oligonucleotides selected by systematic evolution of ligands by exponential enrichment (SELEX), which show great potential in the diagnosis and personalized therapy of cancers, due to their specific advantages over antibodies. In the past years, though great progress has been made in molecular subtyping of breast cancer, it remains a challenge in clinical medicine, which plays a crucial role in the treatment. In this study, a ssDNA aptamer MF3 against MCF-7 breast cancer cells was developed by Cell-SELEX for differentiating breast cancer molecular subtypes, which showed favorable specificity and binding affinity towards MCF-7 cells with a K_d value of 82.25 ± 25.14 nM. The aptamer could not only successfully distinguish MCF-7 breast cancer cells from MDA-MB-231 and SK-BR-3 breast cancer cells and MCF-10A human normal mammary epithelial cells, but also could differentiate MCF-7 cells from other cancer cells or normal cells. Moreover, both in vivo and in vitro fluorescence imaging studies demonstrated that aptamer MF3 was able to distinguish tumor-bearing mice and xenograft tissue sections of MCF-7 breast cancer cells from that of MDA-MB-231 and SK-BR-3 breast cancer cells. All these results suggested that aptamer MF3 is a potential tool for differentiating molecular subtypes and diagnosis of breast cancer.

Tumor masses are three-dimensional (3D). The abnormal physiology of solid tumors is a great barrier to anticancer drug delivery, and the development of effective therapeutic strategies for cancer treatment remains highly challenging. In this study, we have rationally designed IR780 and glucose oxidase (GOx) based poly lactic-co-glycolic acid (PLGA) nanospheres, which can not only selectively accumulate in mitochondria, but also penetrate into 3D tumors deeply at the same time, achieving synergistic treatment of phototherapy and enzyme (GOx)-induced starvation therapy under dual-imaging guidance/monitoring. The lipophilic cationic properties of IR780 enable the nanospheres to penetrate into deep tumor tissues, which has been demonstrated by in vitro 3D tumor modeling and in vivo tumor reconstruction. Meanwhile, the inherent structure of IR780 endows the nanospheres with mitochondrial targeting capability. As mitochondria are susceptible to hyperpyrexia and reactive oxygen species (ROS), mitochondria-targeted phototherapy shows more efficient therapeutic performance. Furthermore, the starvation effect of GOx can cut off the nutrition supply to tumor cells, enhancing the energy metabolism disorder of tumor cells after mitochondrial damage induced by phototherapy, further increasing the damage to tumor cells. In addition, the therapeutic process can be guided/monitored by photoacoustic (PA) and fluorescence (FL) dual imaging. Due to the incorporation of multiple modalities, these nanospheres are promising for cancer theranostics.

Fenton reaction-based reactive oxygen species (ROS) generation provides a new idea for the design of ROS-mediated anticancer agents. Finding ways to increase iron uptake and to elevate the level of H₂O₂ in cells simultaneously is thus crucial to this strategy. Meanwhile, salicylic acid (SA) or its analogue, as the major metabolite of aspirin, has been reported to be closely associated with an intracellular redox-active product. In this work, a PEG-modified nanoscale coordination polymer (PFNC) via the self-assembly of 5-sulfosalicylic acid (SSA) with Fe³⁺ ions has been designed for the first time. The results show that the SSA dissociated from the PFNC can lead to the decrease of GSH and the accumulation of H₂O₂ in cancer cells, and thus elevate cellular ROS via the Fenton reaction. Owing to such intracellular oxidative stress, PFNC-induced ferroptotic cell death was further confirmed. In vitro cytotoxicity studies show that PFNCs display higher cytotoxicity on cancer cells than on normal cells. In vivo experiments further demonstrate that PFNCs not only possess high tumor accumulation, but also significantly inhibit the tumor growth without obvious damage toward the major organs. Based on the results, we expect that this work will provide an inspiration for understanding the role of SA, even aspirin, in the prevention of cancer.