Nowadays, malignancies continue to be a major problem affecting human health worldwide. According to a study of cancer data published by the International Cancer Research Team 2021 in the Journal of Cancer in Clinicians, the global cancer burden remains heavy [1]. As major treatments for cancer, radiotherapy and chemotherapy have many disadvantages such as poor targeting, toxic side effects, rapid drug clearance, time-consuming and money-costing, which also bring physical and psychological trauma to patients [2], [3]. Therefore, it is of great significance to develop targeted tumor treatment options.

Currently, tumor-targeted drug delivery strategies include two modes: passive targeting and active targeting. The former based on the specific characteristics of the tumor vascular system and another based on binding of antitumor agents to their molecular targets or cell-mediated tumor targeting [4]. The use of targeted vectors is one of the methods of active targeting. The specific mechanism of active targeting refers to the fact that tumors are able to produce a large number of factors which can regulate their progression and invasion during their development, such as different types of proteases, growth factors, interleukins, etc., and usually, they are characterized by the overexpression of G protein-coupled receptors and receptors for growth factors, some interleukins, vitamins, transferrin and glycoconjugate fractions. Thus, using certain characteristic molecules on the surface of tumor cells or in the tumor microenvironment as specific receptors of partially functionalized carriers during chemotherapy can enhance the targeting of tumor therapy, leading to prolonged drug accumulation or drug retention in the tumor [4], [5], [6].

In recent years, the research and application of nanoparticles in biomedicine has shown huge promise for cancer treatment. Nanoparticles are synthetic chemical materials with diameters between 1 and 100 nm, they are with unique physicochemical properties and great potential for drug delivery [7], [8], [9]. Studies have shown that nanoparticles as carriers can transport radioactive particles, drugs with small molecules, small interfering RNA (siRNA), DNAzyme, protein molecules, etc. to target cells or target organs [10]. In particular, when transporting chemotherapeutic drugs, due to the rich blood flow, large vascular endothelial gaps, incomplete structure and no functional lymphatic reflux in the vicinity of tumor tissues, nanoparticles can obtain the enhanced permeability and retention (EPR) effect, which promotes the drug enrichment and retention in tumor sites and improves the specific tumor killing effect at the same time [11], [12], [13]. Commonly used nanocarriers such as nanogold, carbon dots, liposomes, paramagnetic iron oxide, and polymers have improved the uptake of drugs by tumor cells, enhanced the water solubility and circulation time of drugs to a certain extent. However, their inherent disadvantages such as difficult degradability, cytotoxicity, and poor drug-release ability still limit their clinical applications. In contrast, nucleic acid nanomaterials (NM) stand out among the series of nanomaterials due to their good biocompatibility, targeting, programmability, and easy degradability [14], [15], [16].

Nucleic acid nanotechnology has been developed rapidly since it was created by Professor Seeman in 1982 [17]. Based on Waston-Crick's “base complementary pairing principle”[18], which is key to achieving programmability of DNA nanostructures, a range of schemes based on adenine–thymine (A-T) and guanine-cytosine (G-C) pairing can be designed to assemble zero, one, two and three-dimensional structures of controlled size. Over the decades, nucleic acid nanomaterials have evolved from the original Tile assembly [19] and DNA origami [20] to the current DNA nanoflowers [21], [22], DNA nanowires [23], [24], DNA nanotrains [25], [26], DNA polyhedra [27], [28], and other ingenious nanostructures. These nucleic acid nanostructures can shine both as molecular probes in biosensors and as drug transport carriers carrying drugs for targeted therapy of diseased cells. In the study of these nucleic acid nanomaterials, the incorporation of an aptamer sequence to enhance the targeting of the material is a common tool during the process of material design.

Nucleic acid aptamer is a single-stranded DNA (ssDNA) or RNA that has been selected from a library of nucleic acid molecules by system systematic evolution of ligands by exponential enrichment technology (SELEX), it’s with excellent specificity and affinity to target and has unique genotypic and phenotypic properties. These characteristics can be easily inherited in in vitro selection experiments, aptamers are also known as “chemical antibodies” [29], [30], [31]. Compared to the widely used protein antibodies, nucleic acid aptamers have many other advantages such as low screening cost, short synthesis cycle, easy modification and preservation, programmability, biocompatibility, low immunogenicity, high affinity, and small size [32], [33], [34], [35]. These good properties make nucleic acid aptamers highly preferred for early tumor diagnosis, targeted therapy, and prognosis observation.

Dox is an anthracycline antibiotic originally isolated from pigment-produced Streptomyces in the early 1960s, [36] which is effective against a variety of cancers, such as cervical cancer, breast cancer, sarcoma, and hematological cancers [37], [38], [39], [40], [41]. Many studies have attributed the antitumor activity of Dox to its ability to embed between the G-C bonds of the DNA helix and/or covalently bind to participate in DNA replication and transcription into proteins, an interaction that leads to the inhibition of DNA, RNA and protein synthesis and ultimately induces apoptosis [42]. Studies have shown that although Dox has a potent killing effect on tumor cells, the use of large amounts of Dox can produce multidirectional toxicity on various tissues and organs of the body due to the lack of targeting, especially with the most significant toxicity on the heart [43], [44]. Since Dox and its derivatives have the property of being embedded between the G-C bonds of the DNA double strand, developing excellent nucleic acid nanocarriers for targeted drug delivery of Dox may be a more effective means than direct treatment with Dox.

Herein, we proposed an intelligent nanomaterial, which contains two simple ssDNA sequences (Sgc8ps and linker). Sgc8ps contains a 5′ end aptamer sequence, a 3′ end palindrome sequence and a sequence at the middle can complementary to the Linker. Sgc8ps contains sgc8 aptamer, The Sgc8-contained nucleic acid nanomaterials (Sgc8NM) was produced from self-assemble by inter- and intra-molecular base complementary pairing, they can deliver Dox to tumor cells to induce apoptosis for efficient anti-tumor effects. In Sgc8NM, the Sgc8 aptamer acts as an intelligent recognizer, which recognizes and binds to the PTK7 protein receptor highly expressed on the surface of certain tumor cells to achieve controlled release of Dox, palindrome sequence and linker sequence take the duty to expand the container of Dox. This controlled release could, reduce the toxicity of Dox to normal cells and greatly improve the drug utilization to a certain extent, which has highly potential applications in the targeted therapy of tumors.