Role of weakly polarized nanoparticles in electroporation

In this study, we present a role for weakly polarized nanoparticles as engineered gene transporters that can enhance electromediated gene delivery. To validate this proof-of-concept, fluorescent poly(ethylene glycol) (PEG)-coated silica nanoparticles (SiNPs) with opposite polarities, SiNPs(RITC)-PEG/PTMA(+) and SiNPs(RITC)-PEG/PMP(-), are used. To investigate the electroporative uptake direction of the nanoparticles-gene complex, we employ microscale electroporation to generate more symmetric and uniform electric fields. The effect of the polarity of the nanoparticles on EGFP gene transfection efficiency in HeLa cells is measured by flow cytometry analysis. The results show that, compared to cationic nanoparticles, anionic nanoparticles have potential as electromediated gene transporters at a low gene concentration. Furthermore, we believe that this finding can be useful for developing a platform that enables electroporation-based gene/drug delivery associated with functional nanoparticles.     

Fluorescent Silica Nanoparticles Targeting Mitochondria: Trafficking in Myeloid Cells and Application as Doxorubicin Delivery System in Breast Cancer Cells

Fluorescent silica nanoparticles (SiNPs) appear to be a promising imaging platform, showing a specific subcellular localization. In the present study, we first investigated their preferential mitochondrial targeting in myeloid cells, by flow cytometry, confocal microscopy and TEM on both cells and isolated mitochondria, to acquire knowledge in imaging combined with therapeutic applications. Then, we conjugated SiNPs to one of the most used anticancer drugs, doxorubicin (DOX). As an anticancer agent, DOX has high efficacy but also an elevated systemic toxicity, causing multiple side effects. Nanostructures are usually employed to increase the drug circulation time and accumulation in target tissues, reducing undesired cytotoxicity. We tested these functionalized SiNPs (DOX-NPs) on breast cancer cell line MCF-7. We evaluated DOX-NP cytotoxicity, the effect on the cell cycle and on the expression of CD44 antigen, a molecule involved in adhesion and in tumor invasion, comparing DOX-NP to free DOX and stand-alone SiNPs. We found a specific ability to release a minor amount of CD44+ extracellular vesicles (EVs), from both CD81 negative and CD81 positive pools. Modulating the levels of CD44 at the cell surface in cancer cells is thus of great importance for disrupting the signaling pathways that favor tumor progression.     

Doxorubicin loading and in vitro release from poly(alkylcyanoacrylate) nanoparticles produced by redox radical emulsion polymerization

The aim of this work was to explore the capacity to load an anticancer agent Doxorubicin (Dox) on new poly(alkylcyanoacrylate) (PACA) nanoparticles prepared by redox radical emulsion polymerization (RREP). These nanoparticles present several advantages compared with the previously described PACA nanoparticles obtained by anionic emulsion polymerization (AEP). Their cytotoxicity was lower and because they do not activate the complement system, they are believed to behave like stealth nanoparticles after intravenous administration. Dox was incorporated during the preparation of the nanoparticles. However, the drug molecules were degraded by cerium IV, which is a strong oxidant agent. To avoid drug degradation, Dox must be loaded by adsorption on preformed nanoparticles. Optimal loading capacity was deduced from a Scatchard's analysis of the Dox adsorption pattern. The loading performance [Loading efficiency (LE) 74%, Loading content (LC) 3.7%], the Dox release and the amount of Dox retained by the new nanoparticles 75% were similar to those of the already well described PACA nanoparticles obtained by AEP (LE 79% and LC 4.2%, drug retention capacity 75%). It can be concluded that the loading and releasing properties make the new nanoparticles an interesting carrier candidate for the in vivo delivery of Dox. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

A Dual‐Targeting Octaguanidine–Doxorubicin Conjugate Transporter for Inducing Caspase‐Mediated Apoptosis on Folate‐Expressing Cancer Cells

An efficient synthetic framework was assembled (G8‐FKE‐FA‐Dox), consisting of a lysosome‐targeting octaguanidine molecular transporter with a cathepsin B (cath B)‐specific peptide substrate, folic acid, and the potent chemotherapeutic drug doxorubicin (Dox). Because the folate receptor (FR) and cath B are overexpressed in malignant cells, this transporter conjugate successfully executed lysosome‐mediated transport of Dox to FR‐positive tumor cells, illustrating this framework as an excellent targeted drug delivery system (TDDS). G8‐FKE‐FA‐Dox was shown to exhibit selective toxicity toward FR‐overexpressing cancer cells, with an IC₅₀ value superior to that of the USFDA‐approved Lipodox^TM and proportional to that of free Dox via selective induction of apoptosis by the activation of caspases 8, 9, and 3. This TDDS was observed to be nontoxic to red blood cells and lymphocytes at neutral pH. Furthermore the tumor‐targeting dissemination pattern of this system was revealed by monitoring the in vivo biodistribution of the carrier (G8‐FKE‐FA‐FL) in normal and FR‐overexpressing tumor‐bearing mice.     

PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells

Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC); however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrP^C, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrP^C-targeting DDSs for targeted drug delivery to CRC. In this study, PrP^C aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrP^C-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrP^C-Apt-functionalized doxorubicin-oligomer-AuNPs (PrP^C-Apt DOA). The PrP^C-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrP^C-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrP^C-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrP^C-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrP^C-Apt DOA targeting could effectively deliver Dox to CRC cells. PrP^C-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox.     

H2O2-Responsive Organosilica-Doxorubicin Nanoparticles for Targeted Imaging and Killing of Cancer Cells Based on a Synthesized Silane-Borate Precursor

Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane-borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol-containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si-Dox@HA nanoparticles with the ability to target CD44-overexpressing cancer cells. The Si-Dox@HA nanoparticles exhibited H₂O₂-responsive release of about 80 % Dox and displayed seven-fold selectivity for killing cancer cells over normal cells, relative to Dox and Si-Dox nanoparticles. Moreover, these Si-Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44-overexpressing cancer cells.     

Acid‐sensitive magnetic nanoparticles as potential drug depots

Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH‐sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.     

The Pro-Apoptotic Effect of Silica Nanoparticles Depends on Their Size and Dose,as Well as the Type of Glioblastoma Cells

Despite intensive investigations, nanoparticle-induced cellular damage is an important problem that has not been fully elucidated yet. Here, we report that silica nanoparticles (SiNPs) demonstrated anticancer influence on glioblastoma cells by the induction of apoptosis or necrosis. These effects are highly cell type-specific, as well as dependent on the size and dose of applied nanoparticles. Exposure of LN-18 and LBC3 cells to different sizes of SiNPs—7 nm, 5–15 nm, or 10–20 nm—at dosages, ranging from 12.5 to 1000 µg/mL, for 24 and 48 h reduced the viability of these cells. Treatment of LN-18 and LBC3 cells with 7 nm or 10–20 nm SiNPs at doses ≥50 µg/mL caused a strong induction of apoptosis, which is connected with an increase of intracellular reactive oxygen species (ROS) production. The 5–15 nm SiNPs exhibited distinct behavior comparing to silica nanoparticles of other studied sizes. In contrast to LBC3, in LN-18 cells exposed to 5–15 nm SiNPs we did not observe any effect on apoptosis. These nanoparticles exerted only strong necrosis, which was connected with a reduction in ROS generation. This suggests that SiNPs can trigger different cellular/molecular effects, depending on the exposure conditions, the size and dose of nanoparticles, and cell type of glioblastoma.     

pH‐responsive poly(ethylene glycol)‐poly(ϵ‐caprolactone)‐poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide‐based block copolymer, poly(ethylene glycol)₂₀₀₀‐poly(?‐caprolactone)₆₀₀₀‐poly(glutamic acid)₁₀₀₀ (PEG₂₀₀₀‐PCL₆₀₀₀‐PGA₁₀₀₀), was investigated. The copolymer was synthesized via ring‐opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self‐assemble into aggregates and the critical aggregation concentration was 0.23 mg mL^?1. Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox‐loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH‐responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST‐1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48 h. The results also showed that PolyDox appeared to induce a higher anti‐tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid‐phase endocytosis pathway. © 2017 Society of Chemical Industry     

Silica Nanoparticles Inhibit Responses to ATP in Human Airway Epithelial 16HBE Cells

Because of their low cost and easy production, silica nanoparticles (SiNPs) are widely used in multiple manufacturing applications as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about the toxicity of this nanomaterial. SiNPs affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of SiNPs on the responses of 16HBE14o- cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca²⁺ concentration. Upon stimulation with extracellular ATP, these cells displayed a concentration-dependent increase in intracellular Ca²⁺, which was mediated by release from intracellular stores. SiNPs inhibited the Ca²⁺ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. SiNPs-induced inhibition is independent from the increase in intracellular Ca²⁺ they produce, is largely irreversible and occurs via a non-competitive mechanism. These findings suggest that SiNPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses.     

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4–254.2 nm with PDI ranging between 0.279–0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.     

以壳聚糖为基质的智能电荷翻转体系用于紫杉醇的高效输送

通过在羧甲基壳聚糖纳米球(CNP)表面修饰三(2-氨基乙基)胺(TAEA)及2,3-二甲基马来酸酐(DMMA),得到针对肿瘤微酸环境响应的智能电荷翻转体系(CNP:TAEA:DMMA-纳米球),并用于难溶性抗肿瘤药物紫杉醇(PTX)的高效输送. 结果表明,所制纳米球在正常体液(pH 7.4)条件下能保留其负电性(-11 mV),从而减少被巨噬细胞J774A.1摄取;而在肿瘤部位的微酸环境(pH 6.8)下,其表面负电性(-34.8 mV)可迅速转化为正电性(+5 mV),促进被肿瘤细胞LLC摄取,提高肿瘤细胞内的药物浓度. 与市售注射剂相比,纳米球展现出良好的生物相容性,对肿瘤细胞杀伤效果也明显提高,其半抑制浓度从11.3降低至4.09 mg/mL,实现了PTX的高效输送.     

Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution

Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments.     

Linear and Non-Linear Optical Imaging of Cancer Cells with Silicon Nanoparticles

New approaches for visualisation of silicon nanoparticles (SiNPs) in cancer cells are realised by means of the linear and nonlinear optics in vitro. Aqueous colloidal solutions of SiNPs with sizes of about 10–40 nm obtained by ultrasound grinding of silicon nanowires were introduced into breast cancer cells (MCF-7 cell line). Further, the time-varying nanoparticles enclosed in cell structures were visualised by high-resolution structured illumination microscopy (HR-SIM) and micro-Raman spectroscopy. Additionally, the nonlinear optical methods of two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS) with infrared laser excitation were applied to study the localisation of SiNPs in cells. Advantages of the nonlinear methods, such as rapid imaging, which prevents cells from overheating and larger penetration depth compared to the single-photon excited HR-SIM, are discussed. The obtained results reveal new perspectives of the multimodal visualisation and precise detection of the uptake of biodegradable non-toxic SiNPs by cancer cells and they are discussed in view of future applications for the optical diagnostics of cancer tumours.     

Poly[N-(2-hydroxypropyl)methacrylamide]-Modified Magnetic γ-F2O3 Nanoparticles Conjugated with Doxorubicin for Glioblastoma Treatment

With the aim to develop a new anticancer agent, we prepared poly[N-(2-hydroxypropyl)methacrylamide-co-methyl 2-methacrylamidoacetate] [P(HP-MMAA)], which was reacted with hydrazine to poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-hydrazinyl-2-oxoethyl)methacrylamide] [P(HP-MAH)] to conjugate doxorubicin (Dox) via hydrazone bond. The resulting P(HP-MAH)-Dox conjugate was used as a coating of magnetic γ-Fe₂O₃ nanoparticles obtained by the coprecipitation method. In vitro toxicity of various concentrations of Dox, P(HP-MAH)-Dox, and γ-Fe₂O₃@P(HP-MAH)-Dox nanoparticles was determined on somatic healthy cells (human bone marrow stromal cells hMSC), human glioblastoma line (GaMG), and primary human glioblastoma (GBM) cells isolated from GBM patients both at a short and prolonged exposition time (up to 7 days). Due to hydrolysis of the hydrazone bond in acid milieu of tumor cells and Dox release, the γ-Fe₂O₃@P(HP-MAH)-Dox nanoparticles significantly decreased the GaMG and GBM cell growth compared to free Dox and P(HP-MAH)-Dox in low concentration (10 nM), whereas in hMSCs it remained without effect. γ-F₂O₃@PHP nanoparticles alone did not affect the viability of any of the tested cells.     

Novel Hybrids of Polystyrene Nanoparticles and Silica Nanoparticles-Grafted-Graphite Via Modified Technique

We have designed polystyrene nanoparticles through modified nanoprecipitation cosolvent evaporation technique and conventional nanoprecipitation and solvent evaporation. Polystyrene nanoparticles were embedded with silica nanoparticles and graphite to analyze scope of nanoprecipitation cosolvent evaporation. Ultraviolet–visible spectroscopic revealed decreased band gap of polystyrene nanoparticles obtained via nanoprecipitation cosolvent evaporation. Scanning electron microscopic showed uniform morphology of polystyrene nanoparticles and polystyrene nanoparticles-based nanocomposites engendered by nanoprecipitation cosolvent evaporation. X-ray diffraction disclosed presence of crystalline domains due to silica nanoparticles content in amorphous structure. Glass transition temperature was increased from 94 (polystyrene) to 124°C (PSNPs/SiNPs 0.6) and 137°C (PSNPs/SiNPs/G 0.6) with filler loading. Electrical conductivity of PSNPs/SiNPs/G 0.6 was also found to be higher (1.53 S/cm).     

pH‐sensitive Podophyllotoxin carrier for cancer cells specific delivery

A pH‐sensitive drug targeting system for solid tumors was established based on N‐isopropylacrylamide (NIPAAm) and chitosan conjugates. The mass ratio of NIPAAm and chitosan was adjusted to obtain super pH‐sensitive characteristic and the structure was studied by using Fourier transform infrared spectroscope to confirm the successful synthesis of the nanoparticles. The pH‐sensitive and drug release characteristics in vitro were studied as well. Human lung cancer cells A‐549 and human fibroblast were used to test the biocompatibility of blank and Podophyllotoxin (POD) loaded nanoparticles further to certificate the reliability of targeting acidic tumor extracellular pH. Results revealed that when charge ratio between NIPAAm and CS achieve 4:1(w/w), the drug‐loaded nanoparticles, which diameters ranged from 50 to 150 nm, exhibited super pH‐sensitive responses to tumor pH. Encapsulation and loading efficiencies were 63.7% and 2.4%, respectively. The cumulative release rate of POD, which significantly enhanced at pH 6.8 while decreased rapidly either below pH 6.5 or above pH 6.9 at 37°C. At pH 6.8, POD‐loaded nanoparticles showed cytotoxicity in MTT test and fluorescence microscopic study, comparable to that of free POD at the same POD concentrations, whereas at pH 7.4 there was little cytotoxicity at the tested concentration range. Thereby, the atoxic PNIPAAm‐g‐chitosan nanoparticle has the potentiality as a novel anticancer drugs carrier. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers     

Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells

Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.     

Mortality response of folate receptor-activated,PEG–functionalized TiO2 nanoparticles for doxorubicin loading with and without ultraviolet irradiation

TiO₂ nanoparticles (NPs) were synthesized by hydrothermal assisted sol–gel technique. In the next step, as-synthesized NPs were modified by poly ethylene glycol (PEG). Then, folic acid (FA) was conjugated to TiO₂–PEG. Finally, Doxorubicin (Dox) as an anticancer drug was loaded on as-prepared TiO₂–PEG–FA nanocarrier. The optimization of TiO₂ and FA concentration and the influence of ultraviolet (UV) irradiation on photocatalytic activity of nanocarrier and Dox loaded carrier were assessed by utilizing the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT)-assay method.