PSi NPs Research Articles

Photothermal therapy and cell imaging tracking of porous silicon nanoparticle by magnesiothermic reduction and surface modification

The synthesis of silicon nanoparticles (PSi NPs) from silica nanoparticles (SiO₂) via magnesium (Mg) reduction is a promising technique due to its simplicity and cost-effectiveness. In this study, silica is utilized as the primary precursor and is subjected to a reduction process using magnesium powder as the reducing agent. By covalently attaching Fluorescein Isothiocyanate (FITC) to the surface of PSi NPs, we aim to enhance their fluorescence intensity and stability while also improving their surface reactivity and biocompatibility. The modified PSi NPs system was characterized using various microscopic techniques, Raman spectra, porosity and morphology analysis, Zeta potential, and analysis of organic functional groups to confirm successful conjugation and to evaluate changes in surface morphology, fluorescence properties, and colloidal stability. By leveraging the inherent photothermal conversion efficiency of PSi NPs, we explore their capacity to generate localized heat upon near-infrared (NIR) light irradiation, effectively inducing cancer cell apoptosis. Concurrently, the natural fluorescence of PSi NPs is harnessed to enable high-resolution imaging, facilitating real-time tracking and monitoring of therapeutic processes. The PSi NPs were subjected to a series of in vitro experiments to assess their photothermal efficiency, cytotoxicity, and imaging capabilities. Results demonstrate that PSi NPs exhibit excellent photothermal effects, leading to significant cell death in targeted cancer cells upon NIR exposure, while their fluorescence properties provide clear and detailed imaging. These findings highlight the potential of PSi NPs as multifunctional agents in cancer therapy, combining effective photothermal treatment with non-invasive imaging, thereby enhancing the precision and efficacy of therapeutic interventions.

Biomimetic Inorganic Nanovectors as Tumor-Targeting Theranostic Platform against Triple-Negative Breast Cancer.

Mesoporous silicon nanoparticles (PSi NPs) are promising platforms of nanomedicine because of their good compatibility, high payload capacities of anticancer drugs, and easy chemical modification. Here, PSi surfaces were functionalized with bisphosphonates (BP) for radiolabeling, loaded with doxorubicin (DOX) for chemotherapy, and the NPs were coated with cancer cell membrane (CCm) for homotypic cancer targeting. To enhance the CCm coating, the NP surfaces were covered with polyethylene glycol prior to the CCm coating. The effects of the BP amount and pH conditions on the radiolabeling efficacy were studied. The maximum BP was (2.27 wt%) on the PSi surfaces, and higher radiochemical yields were obtained for 99mTc (97% ± 2%) and 68Ga (94.6% ± 0.2%) under optimized pH conditions (pH = 5). The biomimetic NPs exhibited a good radiochemical and colloidal stability in phosphate-buffered saline and cell medium. In vitro studies demonstrated that the biomimetic NPs exhibited an enhanced cellular uptake and increased delivery of DOX to cancer cells, resulting in better chemotherapy than free DOX or pure NPs. Altogether, these findings indicate the potential of the developed platform for cancer treatment and diagnosis.

A Bioactive Disintegrable Polymer Nanoparticle for Synergistic Vascular Anticalcification.

Although poly(aspartic acid) (PASP), a strong calcium chelating agent, may be potentially effective in inhibition of vascular calcification, its direct administration may lead to side effects. In this study, we employed polysuccinimide, a precursor of PASP, to prepare targeted polysuccinimide-based nanoparticles (PSI NPs) that not only acted as a prodrug but also functioned as a carrier of additional therapeutics to provide powerful synergistic vascular anticalcification effect. This paper shows that chemically modified PSI-NPs can serve as effective nanocarriers for loading of hydrophobic drugs, in addition to anticalcification and antireactive oxygen species (anti-ROS) activities. Curcumin (Cur), with high loading efficiency, was encapsulated into the NPs. The NPs were stable for 16 h in physiological conditions and then slowly dissolved/hydrolyzed to release the therapeutic PASP and the encapsulated drug. The drug release profile was found to be in good agreement with the NP dissolution profile such that complete release occurred after 48 h at physiological conditions. However, under acidic conditions, the NPs were stable, and Cur cumulative release reached only 30% after 1 week. Though highly effective in the prevention of calcium deposition, PSI NPs could not prevent the osteogenic trans-differentiation of vascular smooth muscle cells (VSMCs). The presence of Cur addressed this problem. It not only further reduced ROS level in macrophages but also prevented osteogenic differentiation of VSMCs in vitro. The NPs were examined in vivo in a rat model of vascular calcification induced by kidney failure through an adenine diet. The inclusion of Cur and PSI NPs combined the therapeutic effects of both. Cur-loaded NPs significantly reduced calcium deposition in the aorta without adversely affecting bone integrity or noticeable side effects/toxicity as examined by organ histological and serum biochemistry analyses.

Poly(succinimide) nanoparticles as reservoirs for spontaneous and sustained synthesis of poly(aspartic acid) under physiological conditions: potential for vascular calcification therapy and oral drug delivery.

This paper describes the preparation of poly(succinimide) nanoparticles (PSI NPs) and investigates their properties and characteristics. Employing direct and inverse precipitation methods, stable PSI NPs with tunable size and narrow dispersity were prepared without the use of any stabilizer or emulsifier. It was demonstrated that PSI NPs convert to poly(aspartic acid) (PASP) gradually under physiological conditions (37 °C, pH 7.4), while remaining stable under mildly acidic conditions. The dissolution profile was tuned and delayed by chemical modification of PSI. Through grafting a fluorophore to the PSI backbone, it was also demonstrated that such a spontaneous conversion could offer great potential for oral delivery of therapeutic agents to the colon. Sustained PASP synthesis also contributed to a sustained reduction of reactive oxygen species induced by iron. Furthermore, PSI NPs effectively prevented in vitro calcification of smooth muscle cells. This was attributed to the chelation of calcium ions to PASP, thereby inhibiting calcium deposition, because under cell culture conditions PSI NPs serve as reservoirs for the sustained synthesis of PASP. Overall, this study sheds light on the preparation and features of biocompatible and biodegradable PSI-based NPs and paves the way for further research to discover as-yet unfulfilled potential of this polymer in the form of nanoparticles.

Development of an amperometric biosensor for dopamine using novel mesoporous silicon nanoparticles fabricated via a facile stain etching approach

Mesoporous silicon (PSi) modified glassy carbon electrode (GCE) was studied for the first time for efficient detection of dopamine (DA). A facile stain etching method was used to synthesize the single crystalline PSi nanoparticles, which was confirmed by the SAED. The morphological study of PSi NPs by FESEM and TEM showed the random distribution of pores with less than 25 nm pore size. The X-ray diffraction (XRD), Raman spectra, and Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were also used in characterizing the PSi NPs. The-as fabricated PSi NPs modified GCE biosensor can measure a wide range of dopamine (0.5–333.3 μM) in phosphate buffer solution (PBS) with a sensitivity value of 0.2715 μAμM−1cm−2 with an extremely low limit of detection (LOD) of 3.2 nM. This non-enzymatic dopamine biosensor was also tested for the possible impact of common interfering substances, which showed very good selectivity. The current modified electrode was further employed to analyze human blood serums and dopamine hydrochloride injection samples to detect DA, where it showed very acceptable analytical results. Additionally, the current PSi/GCE biosensor showed exceptional reproducibility, repeatability, and long-term stability.

Antiviral adsorption activity of porous silicon nanoparticles against different pathogenic human viruses

New viral infections, due to their rapid spread, lack of effective antiviral drugs and vaccines, kill millions of people every year. The global pandemic SARS-CoV-2 in 2019–2021 has shown that new strains of viruses can widespread very quickly, causing disease and death, with significant socio-economic consequences. Therefore, the search for new methods of combating different pathogenic viruses is an urgent task, and strategies based on nanoparticles are of significant interest. This work demonstrates the antiviral adsorption (virucidal) efficacy of nanoparticles of porous silicon (PSi NPs) against various enveloped and non-enveloped pathogenic human viruses, such as Influenza A virus, Poliovirus, Human immunodeficiency virus, West Nile virus, and Hepatitis virus. PSi NPs sized 60 nm with the average pore diameter of 2 nm and specific surface area of 200 m2/g were obtained by ball-milling of electrochemically-etched microporous silicon films. After interaction with PSi NPs, a strong suppression of the infectious activity of the virus-contaminated fluid was observed, which was manifested in a decrease in the infectious titer of all studied types of viruses by approximately 104 times, and corresponded to an inactivation of 99.99% viruses in vitro. This sorption capacity of PSi NPs is possible due to their microporous structure and huge specific surface area, which ensures efficient capture of virions, as confirmed by ELISA analysis, dynamic light scattering measurements and transmission electron microscopy images. The results obtained indicate the great potential of using PSi NPs as universal viral sorbents and disinfectants for the detection and treatment of viral diseases.

Quantum-Confinement Effect in Silicon Nanocrystals during Their Dissolution in Model Biological Fluids

In present work, we studied the mechanisms of dissolution of porous silicon nanoparticles (PSi NPs) during their incubation in model liquids, i.e. water and phosphate buffered saline (PBS) at 37°С. The methods of transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy, and Raman spectroscopy were used. According to TEM images, PSi NPs consist of silicon nanocrystals (nc-Si) 2–10 nm in size and pores. It is shown that incubation of PSi NPs in water leads to enhancement of their PL, accompanied by a slight decrease in the size of nc-Si, which is associated with the passivation of defects and stabilization of the oxide shell of nanocrystals. During incubation in PBS, a significant quenching of PL and disappearance Raman signal of the PSi NPs took place. That indicates rapid dissolution of PSi NPs. We presented phenomenological model describing how quantum-confinement effect affects properties of nc-Si during their dissolution.

Квантово-размерный эффект в кремниевых нанокристаллах при их растворении в модельных биологических жидкостях

In present work, we studied the mechanisms of dissolution of porous silicon nanoparticles (PSi NPs) during their incubation in model liquids, i.e. water and phosphate buffered saline (PBS) at 37 С. The methods of transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy, and Raman spectroscopy were used. According to TEM images, PSi NPs consist of silicon nanocrystals (nc-Si) 2-10 nm in size and pores. It is shown that incubation of PSi NPs in water leads to enhancement of their PL, accompanied by a slight decrease in the size of nc-Si, which is associated with the passivation of defects and stabilization of the oxide shell of nanocrystals. During incubation in PBS, a significant quenching of PL and disappearance Raman signal of the PSi NPs took place. That indicates rapid dissolution of PSi NPs. We presented phenomenological model describing how quantum-confinement effect affects properties of nc-Si during their dissolution.

Tandem-Mass-Tag Based Proteomic Analysis Facilitates Analyzing Critical Factors of Porous Silicon Nanoparticles in Determining Their Biological Responses under Diseased Condition.

The analysis of nanoparticles’ biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio–nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro‐inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor κB pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease‐specific or personalized manner.

Biodegradation model of porous silicon nanoparticles

Development of porous silicon-based drug delivery systems for theranostics requires a precise control of their biodegradation. Thus, we propose a model for the biodegradation of porous silicon nanoparticles (PSi NPs) based on a diffusion equation combined with Nernst-Brunner mass transfer equation describing the dissolution of silicon and formation of silicic acid (SA). The spatiotemporal distributions of PSi NP porosity and SA concentration were calculated. The model was successfully applied to fitting a great variety of experimental data on more than 10 factors influencing the PSi NP biodegradation kinetics, such as the morphology of PSi NPs, surface composition, properties of surrounding media and protective coating layer. Two principal regimes were found out for systems with either diffusion or dissolution dominating over each other. The results of simulations revealed the values of several important parameters, which are hard to be measured experimentally.

Site-Specific 111In-Radiolabeling of Dual-PEGylated Porous Silicon Nanoparticles and Their In Vivo Evaluation in Murine 4T1 Breast Cancer Model.

Polyethylene glycol (PEG) has been successfully used for improving circulation time of several nanomaterials but prolonging the circulation of porous silicon nanoparticles (PSi NPs) has remained challenging. Here, we report a site specific radiolabeling of dual-PEGylated thermally oxidized porous silicon (DPEG-TOPSi) NPs and investigation of influence of the PEGylation on blood circulation time of TOPSi NPs. Trans-cyclooctene conjugated DPEG-TOPSi NPs were radiolabeled through a click reaction with [111In]In-DOTA-PEG4-tetrazine (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and the particle behavior was evaluated in vivo in Balb/c mice bearing 4T1 murine breast cancer allografts. The dual-PEGylation significantly prolonged circulation of [111In]In-DPEG-TOPSi particles when compared to non-PEGylated control particles, yielding 10.8 ± 1.7% of the injected activity/g in blood at 15 min for [111In]In-DPEG-TOPSi NPs. The improved circulation time will be beneficial for the accumulation of targeted DPEG-TOPSi to tumors.

Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke

Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.

Biodegradable Porous Silicon Nanocontainers as an Effective Drug Carrier for Regulation of the Tumor Cell Death Pathways.

Nanocontainers based on solid materials have great potential for drug delivery applications. However, since nanocontainer-mediated delivery can alter the drug internalization pathways and metabolism, it is important to find out what are the mechanisms of cancer cell death induced by nanocontainers and, moreover, is it possible to regulate them. Here, we report on the detailed investigation of the internalization kinetics and intracellular spatial distribution of porous silicon nanoparticles (PSi NPs) loaded with doxorubicin (DOX) and response of cancer cells to treatment with DOX-PSi NPs as well as studies of nanocontainer biodegradation by applying various microscopy methods, Raman microspectroscopy and biological experiments with cancer cells of different etiology. The obtained results revealed the absence of toxicity of unloaded PSi NPs to cancer cells up to a concentration of 700 μg/mL during the prolonged incubation time. Thus, given the fact that the nanocontainers themselves are not toxic, it is easy to adjust the dose of the drug that they deliver to the cells. It is shown, that the treatment with DOX-loaded PSi NPs more efficiently eliminates cancer cells in comparison with the free DOX. At the same time, the obtained results demonstrate the possibility of regulating the initiation of apoptosis or necrosis in tumor cells after treatment with different concentrations of DOX-PSi NPs, as revealed by the analysis of the caspase-3 processing, the accumulation of sub-G1 cell fraction, and morphological changes determined by electron and light microscopy. The obtained results are important for future applications of porous silicon nanocontainers in drug delivery for apoptotic pathway-targeted cancer therapy.

Mild thermotherapy and hyperbaric oxygen enhance sensitivity of TMZ/PSi nanoparticles via decreasing the stemness in glioma

BackgroundGlioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence.MethodsPorous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO.ResultsNCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only.ConclusionThese results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.

GDNF mimetics delivery by porous silicon nanoparticles for improved Parkinson’s disease management

Parkinson’s disease is neurodegenerative movement disorder caused byprogressive degeneration of dopaminergic neurons in substantia nigra. Currently, there are no treatments to slow down, stop or reverse the loss of dopaminergic neuros. Glial cell line-derived neurotrophic factor (GDNF) is a protein that has been shown to prevent the death and help to repair the damaged neurons. However, GDNF is a large molecule (about 32 kDa) that cannot cross the blood brain barrier (BBB), and therefore needs to be delivered by intracranial administration, which requires complex and expensive stereotactic surgery. Generally, small molecules are easier to across the BBB than largemolecules. Thus, small molecules with similar biological activity to GDNF(named GDNF mimetics) might be a better approach to translate into the clinic.Several GDNF mimetics (molecular weight 500-600 g/mol), which are able to activate GDNF receptors and support the survival of dopaminergic neurons, have been found, but they have limited aqueous solubility. Porous silicon nanoparticles (PSi NPs) have the ability to improve the solubility and dissolution rate of poorly water-soluble drugs, as well as to enhance the drug permeation across biological barriers. In our study,GDNF mimetics were loaded into thermally oxidized-PSi (TOPSi) NPs, by which the solubility and dissolution rate of GDNF mimetics were considerably enhanced. Luciferase assay, GDNF receptor RET phosphorylation and internal signalling assay showed that the GDNF mimetics delivered by the TOPSi NPs exhibit higher activity than pristine GDNF mimetics, even in the absence of organic solvents.

Multifunctional Nanohybrid Based on Porous Silicon Nanoparticles, Gold Nanoparticles, and Acetalated Dextran for Liver Regeneration and Acute Liver Failure Theranostics

Herein, a novel nanohybridbased on porous silicon, gold nanoparticles (Au NPs), and acetalated dextran (DPSi/DAu@AcDEX) is reported to encapsulate and deliver one drug and increase the computer tomography (CT) signal for acute-liver-failure (ALF) theranostics. A microfluidic-assisted method is used to co-encapsulate different NPs in a single step. By alternating the surface properties of different NPs and by modulating the composition of the organic phase, both PSi and Au NPs are effectively encapsulated into the polymer matrix simultaneously, thus further achieving a multifunctional application. This system can be used to identify pathologically changes in the tissues and selectively deliver drugs to these sites. The loading of a therapeutic compound (XMU-MP-1) improves the drug solubility, precise, in situ drug delivery, and the drug-functioning time. In vivo results confirm a superior treatment effect and better compliance of this newly developed nanoformulation than free compound. This nanosystem plays a crucial role in targeting the lesion area, thus increasing the local drug concentration important for ALF reverse-effect. Moreover, the residence of Au NPs within the matrix further endows our system for CT-imaging. Altogether, these results support that this nanohybrid is a potential theranostic platform for ALF.

Delivery of Flightless I Neutralizing Antibody from Porous Silicon Nanoparticles Improves Wound Healing in Diabetic Mice.

Flightless I (Flii) is elevated in human chronic wounds and is a negative regulator of wound repair. Decreasing its activity improves healing responses. Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold significant promise as healing agents. However, to avoid the need for repeated application in a clinical setting and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. In this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for the controlled release of FnAb to diabetic wounds. We achieve FnAb loading regimens exceeding 250 µg antibody per mg of vehicle. FnAb-loaded pSi NPs increase keratinocyte proliferation and enhance migration in scratch wound assays. Release studies confirm the functionality of the FnAb in terms of Flii binding. Using a streptozotocin-induced model of diabetic wound healing, a significant improvement in healing is observed for mice treated with FnAb-loaded pSi NPs compared to controls, including FnAb alone. FnAb-loaded pSi NPs treated with proteases show intact and functional antibody for up to 7 d post-treatment, suggesting protection of the antibodies from proteolytic degradation in wound fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers.

Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

Lowering of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles for sonodynamic therapy applications

A significant decrease of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles (PSi NPs) with sizes about 100 nm as compared with pure water was observed for ultrasound irradiation (USI) with therapeutic frequency (0.88 MHz) and intensities (about 1 W/cm2). This effect is explained by porous morphology of PSi NPs, which promotes the nucleation of cavitation bubbles. In vitro experiments revealed a suppression of the proliferation of cancer cells with the introduced PSi NPs after exposure to USI related to the enhanced cavitation processes, which led to the cell destruction. The obtained results demonstrate that PSi NPs are prospective for applications as sonosensitizers in mild cancer therapy.

Inhibition of Multidrug Resistance of Cancer Cells by Co‐Delivery of DNA Nanostructures and Drugs Using Porous Silicon Nanoparticles@Giant Liposomes

Biocompatible, multifunctional, stimuli responsive, and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes are assembled on a microfluidic chip as an advanced nano‐in‐micro platform (PSi NPs@giant liposomes), which can co‐load and co‐deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods, and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness show good biocompatibility, high loading capacity, and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. It is demonstrated that the DAO‐E A DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin‐resistant MCF‐7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano‐in‐micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual responsiveness.