Drug Vehicle Research Articles

Near‐infrared light activated core‐shell electrospun nanofibers decorated with photoactive plasmonic nanoparticles for on‐demand smart drug delivery applications

AbstractOver the last few years, traditional drug delivery systems (DDSs) have been transformed into smart DDSs. Recent advancements in biomedical nanotechnology resulted in introducing stimuli‐responsiveness to drug vehicles. Nanoplatforms can enhance drug release efficacy while reducing the side effects of drugs by taking advantage of the responses to specific internal or external stimuli. In this study, we developed an electrospun nanofibrous photo‐responsive DDSs. The photo‐responsivity of the platform enables on‐demand elevated drug release. Furthermore, it can provide a sustained release profile and prevent burst release and high concentrations of drugs. A coaxial electrospinning setup paired with an electrospraying technique is used to fabricate core‐shell PVA‐PLGA nanofibers decorated with plasmonic nanoparticles. The fabricated nanofibers have a hydrophilic PVA and Rhodamine‐B (RhB) core, while the shell is hydrophobic PLGA decorated with gold nanorods (Au NRs). The presence of plasmonic nanoparticles enables the platform to twice the amount of drug release besides exhibiting a long‐term release. Investigations into the photo‐responsive release mechanism demonstrate the system's potential as a “smart” drug delivery platform.

One-Step Phytofabrication Method of Silver and Gold Nanoparticles Using Haloxylon salicornicum for Anticancer, Antimicrobial, and Antioxidant Activities.

Among various routes of metallic nanoparticle (NPs) fabrication, phytosynthesis has significant advantages over other conventional approaches. Plant-mediated synthesis of NPs is a fast, one-step, ecobenign, and inexpensive method with high scalability. Herein, silver (Ag) and gold (Au)-NPs were extracellularly synthesized using aqueous Haloxylon salicornicum (H@Ag-, H@Au-NPs) leaf extracts. GC-MS was performed to analyze the chemical compositions of H. salicornicum extract. H@Ag- and H@Au-NPs were characterized via UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission and scanning electron microscopy, and Zetasizer. H@Ag- and H@Au-NPs have surface plasmon resonance at 435.5 and 530.3 nm, respectively. FTIR and GC-MS data suggest that secondary plant metabolites and hydrocarbons might be responsible for the reduction and stabilization of NPs. XRD demonstrated that both NPs have a crystalline nature. H@Ag-NPs have a uniform spherical shape, whereas H@Au-NPs are spherical with few oval and triangular shapes, and their average nanosizes were 19.1 ± 0.8 and 8.1 ± 0.3 nm, respectively. Hydrodynamic diameters of H@Ag-NPs and H@Au-NPs were 184.7 nm, 56.4, and 295.4 nm, and their potential charges were -24.0 and -24.4 mV, respectively. The inhibitory activity of 500 µg/mL H@Ag- and H@Au-NPs was tested against Sw480, Sw620, HCT-116, and Caco-2 colon cancer cell lines and two normal cell lines, including HFs and Vero. H@Ag-NPs revealed potent anticancer activity against all cancer cells at low concentrations. Sw480 was the most sensitive cell to H@Ag-NPs, whereas Sw620 was the least permeable one. These findings suggested that the antiproliferative activity of H@Ag-NPs is cell-response-dependent and may be influenced by a variety of factors, including the cellular metabolic state, which influences cellular charge and interactions with charged NPs. Although H@Au-NPs were smaller, their reactivity against cancer cells was weak, suggesting that the chemical properties, metal structure, quantity and chemistry of the functional groups on the NP surface may influence their reactivity. The biocidal activity of 1 mg/mL H@Ag- and H@Au-NPs against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Klebsiella pneumoniae was assessed. H@Ag-NPs showed biocidal activity against Gram-positive bacteria compared to Gram-negative bacteria, whereas H@Au-NPs showed no inhibitory activity. FRAP and DPPH assays were used to determine the scavenging activity of the plant extracts and both NPs. H@Ag-NPs (1 mg/mL) had the greatest scavenging activity compared to tested drugs. These findings suggest that H@Ag-NPs are potent anticancer, antibacterial, and antioxidant agents, while H@Au-NPs may be used as a drug vehicle for pharmaceutical applications.

Contribution of surface-associated membranes to pulmonary surfactant-mediated drug delivery.

Pulmonary surfactant (PS) exhibits unique composition and biophysical properties to transport different type of therapeutic molecules. This has motivated its study as an efficient delivery vehicle for various drugs, especially molecules with hydrophobic character. PS is synthesized and secreted to the alveolar space by type II pneumocytes, where it spontaneously adsorbs into the air-liquid interface to reduce the surface tension. The adsorbed surfactant film is constituted by an interfacial monolayer with multi-layered membranes associated to it. Surfactant proteins SP-B and SP-C are responsible for maintaining the contact between these reservoirs and the interfacial layer. In order to study whether the multi-layered and multi-vesicular structures spread along the interface together with the interfacial monolayer, potentially serving as a vehicle for drugs, we have designed a novel vehiculization surface balance that connects a donor with a recipient compartment through a long interfacial pathway. Typically, the vehiculization of drugs mediated by PS has been evaluated in vitro by setups that combine different compartments through interfacial paper bridges. By incorporating a lipid fluorescent probe and the model hydrophobic drug Budesonide (BUD) into a porcine derived PS or into proteo-lipid vesicles, we determined that the amount of material transferred from a donor to a recipient compartment was substantially reduced due to the barrier imposed by the paper bridge. The bridge reduced the spreading to a simpler interfacial layer, while our novel setup reveals that a larger three-dimensional layer of liquid may facilitate the spreading of associated membranes and surfactant/drug complexes. We have determined that the three-dimensional structures associated to the interfacial layer spread along the air-liquid interface and entail an important contribution to the transport of lipids and drugs in surfactant-mediated delivery.

Polyphosphazenes—A Promising Candidate for Drug Delivery, Bioimaging, and Tissue Engineering: A Review

AbstractSynthetic polymer materials have been surged to the forefront of research in the fields of tissue engineering, drug delivery, and biomonitoring in recent years. Biodegradable synthetic polymers are increasingly needed as transient substrates for tissue regeneration and medicine delivery. In contrast to commonly used polymers including polyesters, polylactones, polyanhydrides, poly(propylene fumarates), polyorthoesters, and polyurethanes, biodegradable polyphosphazenes (PPZs) hold great potential for the purposes indicated above. PPZ's versatility in the synthetic process has enabled the production of a variety of polymers with various physico‐chemical, and biological properties have been produced, making them appropriate for biomedical applications. Biocompatible PPZs are often used as scaffolds in the regeneration of skeleton, bones, and other tissues. PPZs have also received special attention as potential drug vehicles of high‐value biopharmaceuticals such as anticancer drugs. Additionally, by incorporating fluorophores into the PPZ backbone to produce photoluminescent biodegradable PPZs, the utility of polyphosphazenes is further expanded as they are used in tracking the regeneration of the target tissue as well as the fate of PPZ based scaffolds or drug delivery vehicles. This review provides a summary of the evolution of PPZ applications in the fields of tissue engineering, drug delivery, and bioimaging in recent 5 years.

A DFT study on the transition metal doped BN and AlN nanocages as a drug delivery vehicle for the cladribine drug

Although considerable progress in chemotherapy drugs has been achieved, adverse side effects, the amount of drug release, and bioavailability are challenging problems that affect the treatment. In this work, the key role of transition metal doped-nanocages as a drug delivery vehicle was closely investigated by density functional theory (DFT) method. Bioavailable transition metal doped (M = Zn, Cu, Fe, Ni) BN and AlN nanocages were considered as a nano-vehicle for the cladribine drug. Electronic properties, topological analysis, electrostatic and vdW potential analysis were studied for complexes of drug-nanocages. The cladribine interacted with nanocages through NH2 and OH groups. Metal doping improved drug delivery features of nanocages through improving the polarity of the system. Among the metal-doped BN and AlN nanocages, ZnAl 11N12 showed the most favorable delivery vehicle for the cladribine with suitable adsorption energy −42.87 and −38.06 kcal/mol in gas and water phases, respectively. The analysis of density of states (DOS), H-L analysis, quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), and vdW potential showed that the nature of interactions between drug and nanocages is weak non-covalent which is beneficial for the release of the drug. The TD-DFT calculation showed that the maximum wavelength of complexes red shifted which is safer for tissues. The recovery time of cladribine under the body temperature is about 0.37 s which is beneficial for drug desorption. This detailed molecular level information could provide rational guidance for the design of novel drug vehicle for the cladribine.

Engineered Extracellular Vesicles as a Targeted Delivery Platform for Precision Therapy.

Extracellular vesicles (EVs)-based cell-free strategy has shown therapeutic potential in tissue regeneration. Due to their important roles in intercellular communications and their natural ability to shield cargos from degradation, EVs are also emerged as novel delivery vehicles for various bioactive molecules and drugs. Accumulating studies have revealed that EVs can be modified to enhance their efficacy and specificity for the treatment of many diseases. Engineered EVs are poised as the next generation of targeted delivery platform in the field of precision therapy. In this review, the unique properties of EVs are overviewed in terms of their biogenesis, contents, surface features and biological functions, and the recent advances in the strategies of engineered EVs construction are summarized. Additionally, we also discuss the potential applications of engineered EVs in targeted therapy of cancer and damaged tissues, and evaluate the opportunities and challenges for translating them into clinical practice.

Metal Nanoparticles to Combat Candida albicans Infections: An Update.

Candidiasis is an opportunistic mycosis with high annual incidence worldwide. In these infections, Candida albicans is the chief pathogen owing to its multiple virulence factors. C. albicans infections are usually treated with azoles, polyenes and echinocandins. However, these antifungals may have limitations regarding toxicity, relapse of infections, high cost, and emergence of antifungal resistance. Thus, the development of nanocarrier systems, such as metal nanoparticles, has been widely investigated. Metal nanoparticles are particulate dispersions or solid particles 10-100 nm in size, with unique physical and chemical properties that make them useful in biomedical applications. In this review, we focus on the activity of silver, gold, and iron nanoparticles against C. albicans. We discuss the use of metal nanoparticles as delivery vehicles for antifungal drugs or natural compounds to increase their biocompatibility and effectiveness. Promisingly, most of these nanoparticles exhibit potential antifungal activity through multi-target mechanisms in C. albicans cells and biofilms, which can minimize the emergence of antifungal resistance. The cytotoxicity of metal nanoparticles is a concern, and adjustments in synthesis approaches or coating techniques have been addressed to overcome these limitations, with great emphasis on green synthesis.

Enhanced skin penetration of Finasteride loaded DMSO-liposomes for the treatment of androgenic alopecia: comparison with conventional liposomes

Long-term treatment with finasteride (FIN) for androgenic alopecia is restricted due to its systemic side effects. To address this problem, DMSO-modified liposomes were prepared in the present study to improve the topical delivery of FIN. DMSO-liposomes were prepared by a modification of the ethanol injection method. It was hypothesized that the permeation-enhancing property of DMSO could promote drug delivery to deeper skin layer where hair follicles are present. Liposomes were optimized by quality by design (QbD) approach and biologically evaluated in a rat model of testosterone-induced alopecia. Optimized DMSO-liposomes were spherical and had mean vesicle size, zeta potential, and entrapment efficiency of 330.1 ± 1.5, −14.52 ± 1.32, and 59.02 ± 1.12%, respectively. Biological evaluation on testosterone-induced alopecia and skin histology shows that follicular density and anagen/telogen (A/T) ratio were increased in rats treated with DMSO-liposomes as compared to FIN-liposomes without DMSO and an alcoholic solution of FIN applied topically. DMSO-liposomes could be promising skin delivery vehicles for FIN or similar drugs.

Extracellular Vesicles Derived From 3D Cultured Antler Stem Cells Serve as a New Drug Vehicle in Osteosarcoma Treatment

Extracellular vesicles (EVs) from antler reserve mesenchymal (RM) cells play an important role in the paracrine regulation during rapid growth of antler without forming a tumor; therefore, RM-EVs become novel materials for anti-tumor studies, such as osteosarcoma treatment. However, the problem of low production of RM-EVs in traditional 2D culture limits its mechanism research and application. In this study, we established an optimal 3D culture system for antler RM cells to produce EVs (3D-RM-EVs). Morphology and property of harvested 3D-RM-EVs were normal compared with EVs from conventional 2D culture, and the miRNA profile in them was basically the same through transcriptome sequencing analysis. Based on the same number of RM cells, the volume of the culture medium collected by 3D cultural system concentrated nearly 30 times, making it more convenient for subsequent purification. In addition, EVs were harvested 30 times in 3D cultural system, greatly increasing the total amount of EVs (harvested a total of 2–3 times in 2D culture). Although 3D-RM-EVs had a limited inhibitory effect on the proliferation of K7M2 cells, the inhibition effect of 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) were more significant than that of positive drug group alone (P < 0.05). Furthermore, in vivo studies showed that 3D-RM-EVs loaded drugs (Ifosfamide + Etoposide) had the most significant tumor inhibition effect, with decreased tumor size, and could slow down body weight loss compared with Ifosfamide + Etoposide (IFO + ET) group. These results demonstrated that 3D-RM-EVs were efficiently prepared from antler RM cells and were effective as drug vehicles for the treatment of osteosarcoma.

Protective Effect of L-carnitine against Cefquinome Sulfate Induced Testicular Damage and Oxidative Stress in Male Albino Rats

The present study was conducted to evaluate the protective effect of L-carnitine (LC) against possible deleterious effects of cefquinome sulfate (CS) on antioxidant capacity, fertility parameters and histopathological findings of reproductive organs in male rats. Therefore, seventy two mature male rats were equally divided into four equal groups as following: The control group of rats was administered two s.c. doses of physiological saline (vehicle of other drugs) (2ml/kg b.wt. once daily for 5 successive days and 2ml/kg b.wt. once daily for 8 successive weeks), the second group was s.c. administered LC (200 mg/kg b.wt. once daily for 8 successive weeks), the third group was s.c. administered CS (50 mg/kg b.wt. once daily for 5 successive days) and the fourth group was s.c. administered CS concomitantly with LC by the same doses. The obtained results showed that administration of CS induced a significant (P≤ 0.05) increase in serum level of Malondialdehyde (MDA) and total sperm abnormalities with significant (P≤ 0.05) decrease in serum level of total antioxidant capacity (TAC), sperm motility and total sperm count. Moreover, CS induced histopathological changes in tissues of testes and epididymis. Conversely, administration of LC concomitantly with CS ameliorates all the previous antioxidant, fertility and histopathological alterations induced by CS. It could be concluded that CS induced some undesired effects on antioxidant activity, fertility parameters and histopathological findings which could be ameliorated by LC in male albino rats.

A robust epoxy nanocomposite with iron oxide decorated cellulose nanofiber as a sustained drug delivery vehicle for antibacterial drugs

Sustainably derived nanoparticles and their nanohybrids are crucial for developing energy efficient polymeric materials.

Narrow response temperature range with excellent reversible shape memory effect for semi-crystalline networks as soft actuators.

Complex and controlled reversible actuation inevitably relies on changing thermal fields (direct or indirect) for semi-crystalline reversible shape memory networks. Unfortunately, the non-tunability of thermal signals often brings potential limitations to actuators' applications. In practice, a wide response temperature range (T-range) formed by Thigh and Tlow in the remarkable reversible actuation is an obvious fact. Herein, we demonstrate the tunability of the transition temperatures while stably maintaining excellent actuation abilities. We further verified that the narrow T-range (24 °C) that had not been reported could present more than 17% reversible strain. Special parameter optimization provides opportunities for potential non-implantable biomedical applications. Therefore, based on target 2W-SMP, a vehicle concept with the drug release and vehicle recovery ability was proposed, proving our approach's feasibility.

Prospect of nanomaterials as antimicrobial and antiviral regimen.

In recent years studies of nanomaterials have been explored in the field of microbiology due to the increasing evidence of antibiotic resistance. Nanomaterials could be inorganic or organic, and they may be synthesized from natural products from plant or animal origin. The therapeutic applications of nano-materials are wide, from diagnosis of disease to targeted delivery of drugs. Broad-spectrum antiviral and antimicrobial activities of nanoparticles are also well evident. The ratio of nanoparticles surface area to their volume is high and that allows them to be an advantageous vehicle of drugs in many respects. Effective uses of various materials for the synthesis of nanoparticles impart much specificity in them to meet the requirements of specific therapeutic strategies. The potential therapeutic use of nanoparticles and their mechanisms of action against infections from bacteria, fungi and viruses were the focus of this review. Further, their potential advantages, drawbacks, limitations and side effects are also included here. Researchers are characterizing the exposure pathways of nano-medicines that may cause serious toxicity to the subjects or the environment. Indeed, societal ethical issues in using nano-medicines pose a serious question to scientists beyond anything.

Nanocapsules of unprecedented internal volume seamed by calcium ions.

The inception of an unprecedented class of voluminous Platonic solids displaying hierarchical geometry based on pyrogallol[4]arene moieties seamed by divalent calcium ion is described. Single-crystal X-ray structural determination has established the highly conserved geometry of two original Ca2+-seamed nanocapsules to be essentially cubic in shape with C-ethylpyrogallol[4]arene units located along the twelve edges of the cube which are then bridged by metallic polyatomic cations ([Ca4Cl]7+ or [Ca(HCO2)Na4]5+) at the six cube faces. The accessible volume of the nanocapsules is ca. 3500 Å3 and 2500 Å3 and is completely isolated from the exterior of the capsules. These remarkable nanocapsule discoveries cast a spotlight on a marginalized area of synthetic materials chemistry and encourage future exploration of diversiform supramolecular assemblies, networks, and capsules built on calcium, with clear benefits deriving from the intrinsic biocompatibility of calcium. Finally, a proof-of-concept is demonstrated for fluorescent reporter encapsulation and sustained release from the calcium-seamed nanocapsules, suggesting their potential as delivery vehicles for drugs, nutrients, preservatives, or antioxidants.

Characterization of Drug Delivery Systems by Transmission Electron Microscopy.

The contribution of electron microscopy, and here, in particular transmission electron microscopy (TEM), to the formulation and understanding of the biological action of drug delivery systems has led to a better insight into the design principles of drug delivery systems. TEM can be applied for particle characterization, for the visualization of the uptake and intracellular pathways of drug vehicles in cells and tissues and more recently can be also applied for the high-resolution investigation of drug-receptor interactions with near-atomic resolution. This chapter introduces basic techniques to optimize imaging quality of soft matter samples, highlights possibilities to study certain aspects of drug delivery applications, and finally provides a short introduction to high-resolution characterization possibilities which recently emerged.

Swelling induced mechanically tough starch-agar based hydrogel as a control release drug vehicle for wound dressing applications.

In recent years, polysaccharide-based hydrogels have received increased attention due to their inherent biodegradability, biocompatibility, and non-toxicity. The feasibility of using polysaccharides for the synthesis of hydrogels is dependent on their noteworthy mechanical strength and cell compatibility, which are required for practical applications, especially for biomedical uses. In this study, we demonstrate a facile synthetic route for the construction of a mechanically tough, biocompatible, and biodegradable hydrogel using polysaccharides such as starch and agar. A synthetic monomer-free hydrogel was synthesized using epichlorohydrin as a cross-linker, and a mechanical strength of 9.49 ± 1.29-6.16 ± 0.37 MPa was achieved. The introduction of agar into the hydrogel resulted in agar dose-dependent swelling-induced mechanical strength. Moreover, along with incredible mechanical strength, the hydrogel also exhibited prominent cell viability against human embryonic kidney cells. In addition, the hydrogel showed good encapsulation efficiency for antibacterial drugs like ciprofloxacin hydrochloride hydrate, with controlled releasing ability over a sustained period. The antibacterial activity of the encapsulated drug was observed against Staphylococcus aureus and Bacillus subtilis bacterial strains. Thus, the studied hydrogel with loaded drug exhibited all the required qualities to be utilized as a promising candidate in wound dressing applications.

A tris(2-aminoethyl)amine-based zinc complex as a highly water-soluble drug carrier for the anti-COVID-19 drug favipiravir: a joint experimental and theoretical study.

Tris(2-aminoethyl)amine (tren) coordinates to a Zn(II) ion to form the [Zn(tren)]2+ cation that accepts a monodentate favipiravir (FAV) anion. The results of this work show that the FAV anion is capable of binding to the [Zn(tren)]2+ cation through either a nitrogen or an oxygen atom (N/O-coordination). The energy decomposition analysis shows that, interestingly, both the strength and nature of the bonds between the [Zn(tren)]2+ cation and the N/O-coordinated FAV anion are almost the same. X-ray crystal structure determinations confirmed the existence of two types of cations in the solid state, [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+. The NMR data, in a DMSO solution, were consistent with either the N-coordinated or the O-coordinated complex, but not a mixture of the two linkage isomers. The theoretical data indicated that the [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+ cations have very similar stability in the gas phase, and in H2O, CH3OH, and DMSO solutions, and can also easily convert from one linkage isomer to the other. The experimental and theoretical data showed that, upon protonation of the above cations under acidic conditions (pH ≈ 3 to 5.5), the drug FAV will be easily released and replaced by a Cl- anion, or an H2O molecule, which will coordinate to the zinc atom showing the potential of [Zn(tren)]2+ as a safe drug vehicle. Molecular docking studies using two well-known molecular docking packages show the relatively strong binding interactions of the [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+ cations with DNA and viral protein macromolecules.

Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels-Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications.

Microfluidic on-chip production of polymeric hydrogel microspheres (MPs) can be designed for the loading of different biologically active cargos and living cells. Among different gelation strategies, ionically crosslinked microspheres generally show limited mechanical properties, meanwhile covalently crosslinked microspheres often require the use of crosslinking agents or initiators with limited biocompatibility. Inverse electron demand Diels Alder (iEDDA) click chemistry is a promising covalent crosslinking method with fast kinetics, high chemoselectivity, high efficiency and no cross-reactivity. Herein, in situ gellable iEDDA-crosslinked polymeric hydrogel microspheres are developed via water-in-oil emulsification (W/O) glass microfluidics. The microspheres are composed of two polyethylene glycol precursors modified with either tetrazine or norbornene as functional moieties. Using a single co-flow glass microfluidic platform, homogenous MPs of sizes 200-600 μm are developed and crosslinked within 2 minutes. The rheological properties of iEDDA crosslinked bulk hydrogels are maintained with a low swelling degree and a slow degradation behaviour under physiological conditions. Moreover, a high-protein loading capacity can be achieved, and the encapsulation of mammalian cells is possible. Overall, this work provides the possibility of developing microfluidics-produced iEDDA-crosslinked MPs as a potential drug vehicle and cell encapsulation system in the biomedical field.

Thermosensitive Liposomal Drug Delivery Systems: A Review

When combined with local hyperthermia or high intensity focused ultrasound, thermosensitive liposomes are a promising technique for externally directing medications to solid tumours. To selectively focus drug delivery to diseased or damaged tissue while reducing drug distribution to vital normal tissues is the main goal of liposomal drug delivery. An overview of temperature-sensitive liposomes is provided in this review. The ability to heat tumours with external energy sources in a controlled and predictable manner makes temperature-sensitive liposomes an especially alluring alternative. The lipids used to make conventional thermosensitive liposomes experience a gel-to-liquid phase shift many degrees above physiological temperature. Lysolipids and artificial temperature-sensitive polymers have recently been used to show how liposomes can be made to be sensitive to temperature. Thermosensitive liposomes (TSL) and localized hyperthermia are potent delivery vehicles for tumor-specific drugs. In addition to chemotherapy, hyperthermia is given to cancer patients to help certain chemotherapeutic medications work more effectively. Using temperature-sensitive liposomes in conjunction with localized hyperthermia, which specifically releases the medicine contained in the heated tumor tissue, can significantly increase the temperature-dependent effect.

Self-assembly of DNA nanospheres with controllable size and self-degradable property for enhanced antitumor chemotherapy

Controllable size, self-degradability and targeting property are important for a precise improvement of anticancer effects and reduction of side effects of drug vehicles. Here, a series of DNA nanospheres with controllable size and self-degradation ability were constructed through the hybridization of two i-motif strands and two linker strands for targeted cancer therapy. DNA nanospheres with different sizes were fabricated by regulating the linker sequence, and their pH-responsive self-degradation property was realized by the introduction of the i-motif strand. Moreover, the ZY11 aptamer was introduced to endow the DNA nanospheres with targeting property toward SMMC-7721 cancer cells. The results revealed that the appropriate size of DNA nanospheres (80 nm) highly promoted the internalization by mammalian cells. The results of DLS, AFM and CD spectra showed that the DNA nanospheres were stable in a physiological environment but they self-degraded in a slightly acidic environment due to the existence of the i-motif strand. Moreover, the fluorescence of DOX@AP-NSs2 was triple at pH = 5.0 than at pH = 7.4, which further confirmed the pH-responsive drug release performance. The above results proved that the use of DOX@AP-NSs2 is a promising approach to accelerate the rapid release of drugs into the tumors and avoid drug leakage into the normal tissue. The results at a cellular level and in vivo confirmed the pH-responsive targeted antitumor effect. Hence, the novel DNA nanospheres with controllable size and self-degradable property represent a potential tool for targeted drug delivery and cancer therapy.