The Cellular Prion Protein: A Promising Therapeutic Target for Cancer

Studies on the cellular prion protein (PrP^C) have been actively conducted because misfolded PrP^C is known to cause transmissible spongiform encephalopathies or prion disease. PrP^C is a glycophosphatidylinositol-anchored cell surface glycoprotein that has been reported to affect several cellular functions such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation. Recently, it has also been reported that PrP^C mediates tumor progression by enhancing the proliferation, metastasis, and drug resistance of cancer cells. In addition, PrP^C regulates cancer stem cell properties by interacting with cancer stem cell marker proteins. In this review, we summarize how PrP^C promotes tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties. In addition, we discuss strategies to treat tumors by modulating the function and expression of PrP^C via the regulation of HSPA1L/HIF-1α expression and using an anti-prion antibody.     

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.     

A bio-inspired gelatin-based pH- and thermal-sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells

Gelatin (Gel)-based pH- and thermal-responsive magnetic hydrogels (MH-1 and MH-2) were designed and developed as novel drug delivery systems (DDSs) for cancer chemo/hyperthermia therapy. For this goal, Gel was functionalized with methacrylic anhydride (GelMA), and then copolymerized with (2-dimethylaminoethyl) methacrylate (DMAEMA) monomer in the presence of methacrylate-end capped magnetic nanoparticles (MNPs) as well as triethylene glycol dimethacrylate (TEGDMA; as crosslinker). Afterward, a thiol-end capped poly(N-isopropylacrylamide) (PNIPAAm-SH) was synthesized through an atom transfer radical polymerization technique, and then attached onto the hydrogel through “thiol-ene” click grafting. The preliminary performances of developed MHs for chemo/hyperthermia therapy of human breast cancer was investigated through the loading of doxorubicin hydrochloride (Dox) as an anticancer agent followed by cytotoxicity measurement of drug-loaded DDSs using MTT assay by both chemo- and chemo/hyperthermia-therapies. Owing to porous morphologies of the fabricated magnetic hydrogels according to scanning electron microscopy images and strong physicochemical interactions (e.g., hydrogen bonding) the drug loading capacities of the MH-1 and MH-2 were obtained as 72 ± 1.4 and 77 ± 1.8, respectively. The DDSs exhibited acceptable pH- and thermal-triggered drug release behaviors. The MTT assay results revealed that the combination of hyperthermia therapy and chemotherapy has synergic effect on the anticancer activities of the developed DDSs.     

Molecular Mechanisms and Tumor Biological Aspects of 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells

5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116R^F10. HCT116R^F10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116R^F10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116R^F10 cells. Interestingly, HCT116R^F10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.     

Strain Typing of Classical Scrapie and Bovine Spongiform Encephalopathy (BSE) by Using Ovine PrP (ARQ/ARQ) Overexpressing Transgenic Mice

Transmissible spongiform encephalopathies (TSE), caused by abnormal prion protein (PrP^Sc), affect many species. The most classical scrapie isolates harbor mixtures of strains in different proportions. While the characterization of isolates has evolved from using wild-type mice to transgenic mice, no standardization is established yet. Here, we investigated the incubation period, lesion profile and PrP^Sc profile induced by well-defined sheep scrapie isolates, bovine spongiform encephalopathy (BSE) and ovine BSE after intracerebral inoculation into two lines of ovine PrP (both ARQ/ARQ) overexpressing transgenic mice (Tgshp IX and Tgshp XI). All isolates were transmitted to both mouse models with an attack rate of almost 100%, but genotype-dependent differences became obvious between the ARQ and VRQ isolates. Surprisingly, BSE induced a much longer incubation period in Tgshp XI compared to Tgshp IX. In contrast to the histopathological lesion profiles, the immunohistochemical PrP^Sc profiles revealed discriminating patterns in certain brain regions in both models with clear differentiation of both BSE isolates from scrapie. These data provide the basis for the use of Tgshp IX and XI mice in the characterization of TSE isolates. Furthermore, the results enable a deeper appreciation of TSE strain diversity using ovine PrP overexpressing transgenic mice as a biological prion strain typing approach.     

Construction of magnetic-targeted and NIR irradiation-controlled drug delivery platform with Fe3O4@Au@SiO2 nanospheres

Near-infrared (NIR) light has great potential in biomedical applications due to its advantages of deep penetration depth and low photodamage to biological tissues. In this paper, we constructed a novel core-shell structured drug nanocarrier, Fe₃O₄@Au@SiO₂, for the controlled delivery of etoposide (VP16), a chemotherapeutic drug for cancer patients. The novel core-shell structured drug delivery platform is composed of a mesoporous silica shell and a magnetic Fe₃O₄ core using Au nanoparticles (AuNPs) as the interlayer, which is characterized by atomic force microscopy (AFM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, N₂ adsorption/desorption isotherms and the magnetic measurements with vibrating-sample magnetometer (VSM). The synergistic effects of AuNPs, mesoporous silica and Fe₃O₄ make the core-shell structured nanocomposites an excellent candidate for targeted and NIR light irradiation-controlled drug delivery. For the proposed nanocarrier of VP16, the mesopores in silica can enhance the encapsulation capacity of the nanocarrier and the AuNPs can effectively convert the NIR light into heat to speed up the drug deliver; meanwhile, the incorporation of Fe₃O₄ with high magnetization to the drug delivery platform realize drug targeting under an applied external magnetic field.     

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     

Prion Infectivity and PrPBSE in the Peripheral and Central Nervous System of Cattle 8 Months Post Oral BSE Challenge

After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous system. However, the timeline of this progression has thus far remained widely undetermined. Previous studies were focused on later time points after oral exposure of animals that were already 4 to 6 months old when challenged. In contrast, in this present study, we have orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible BSE infectivity and/or PrP^BSE in peripheral nervous tissues during the first eight months post-inoculation (mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse bioassay, while PrP^BSE depositions were analyzed by immunohistochemistry (IHC) and by protein misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrP^BSE and BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed, and pharmaceutical products produced from young calves.     

S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116^p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.     

Ethanolamine Is a New Anti-Prion Compound

Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP^Sc. PrP^Sc is produced through conformational conversion of the cellular isoform of prion protein, PrP^C, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP^Sc levels when cultured in advanced Dulbecco’s modified eagle medium (DMEM) but not in classic DMEM. PrP^C levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP^Sc levels in N2aC24L1-3 cells, but not PrP^C levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.     

Efficient pH Dependent Drug Delivery to Target Cancer Cells by Gold Nanoparticles Capped with Carboxymethyl Chitosan

Doxorubicin (DOX) was immobilized on gold nanoparticles (AuNPs) capped with carboxymethyl chitosan (CMC) for effective delivery to cancer cells. The carboxylic group of carboxymethyl chitosan interacts with the amino group of the doxorubicin (DOX) forming stable, non-covalent interactions on the surface of AuNPs. The carboxylic group ionizes at acidic pH, thereby releasing the drug effectively at acidic pH suitable to target cancer cells. The DOX loaded gold nanoparticles were effectively absorbed by cervical cancer cells compared to free DOX and their uptake was further increased at acidic conditions induced by nigericin, an ionophore that causes intracellular acidification. These results suggest that DOX loaded AuNPs with pH-triggered drug releasing properties is a novel nanotheraputic approach to overcome drug resistance in cancer.     

Synthesis of PEGylation hydroxyapatite drug delivery system and its dual channels fluorescence imaging

PEGylated drug delivery systems (DDSs) can overcome the side effects of traditional chemotherapy by enhancing drug permeability and retention (EPR) effects. In this work, DOX@HAP (hydroxyapatite) was initially fabricated via the coprecipitation and hydrothermal method, further functionalized with Cy (cyanine) by coupling reaction of APTES and then introduced hydrophilic PEG chains by using copper(I)-catalyzed alkyne–azide cycloaddition reaction. Physicochemical properties including the morphology, particle size and phase composition, were characterized by TEM, SEM, particle size analyzer, FTIR, XPS and XRD. The encapsulation efficiency and drug release profile of DOX@HAP-Cy-PEG were analyzed by UV-Vis spectrophotometry. Furthermore, the cellular uptake of DOX@HAP-Cy-PEG nanoparticles in Hela and HepG2 cells was monitored by the dual channels fluorescence imaging of DOX and Cy. The results showed that DOX@HAP-Cy-PEG nanoparticles could be used to real-time monitor the dynamic distribution of DDSs in Hela and HepG2 cells by dual channels.     

PEG化羟基磷灰石纳米体系的制备及双通道荧光成像

PEG化的药物递送系统（DDSs）可以通过增强药物的渗透性和滞留性（EPR）效应克服传统化疗的副作用。利用共沉淀法和水热法制备纳米粒子DOX@HAP,进一步通过偶联反应修饰菁染料（Cy）,通过铜（I）催化的炔-叠氮化物环加成反应修饰PEG链,构建了纳米制剂DOX@HAP-Cy-PEG。通过透射电子显微镜（TEM）、扫描电子显微镜（SEM）、粒度分析仪、傅里叶红外光谱仪（FTIR）、X射线光电子能谱仪（XPS）和X射线衍射仪（XRD）对该纳米载药体系的形貌、粒径、物相组成进行表征分析。利用紫外-可见（UV-Vis）分光光度法测定了该纳米材料的药物负载量以及体外药物释放曲线。进一步,利用DOX和Cy双通道荧光成像,监测DDSs在Hela和HepG2细胞中的摄取行为。表明DOX@HAP-Cy-PEG纳米载药体系有望作为一种新型的治疗与示踪一体化的抗癌纳米制剂。     

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.     

A green chemistry approach for synthesizing biocompatible gold nanoparticles

Gold nanoparticles (AuNPs) are a fascinating class of nanomaterial that can be used for a wide range of biomedical applications, including bio-imaging, lateral flow assays, environmental detection and purification, data storage, drug delivery, biomarkers, catalysis, chemical sensors, and DNA detection. Biological synthesis of nanoparticles appears to be simple, cost-effective, non-toxic, and easy to use for controlling size, shape, and stability, which is unlike the chemically synthesized nanoparticles. The aim of this study was to synthesize homogeneous AuNPs using pharmaceutically important Ganoderma spp. We developed a simple, non-toxic, and green method for water-soluble AuNP synthesis by treating gold (III) chloride trihydrate (HAuCl₄) with a hot aqueous extract of the Ganoderma spp. mycelia. The formation of biologically synthesized AuNPs (bio-AuNPs) was characterized by ultraviolet (UV)-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the biocompatibility of as-prepared AuNPs was evaluated using a series of assays, such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation (ROS) in human breast cancer cells (MDA-MB-231). The color change of the solution from yellow to reddish pink and strong surface plasmon resonance were observed at 520 nm using UV-visible spectroscopy, and that indicated the formation of AuNPs. DLS analysis revealed the size distribution of AuNPs in liquid solution, and the average size of AuNPs was 20 nm. The size and morphology of AuNPs were investigated using TEM. The biocompatibility effect of as-prepared AuNPs was investigated in MDA-MB-231 breast cancer cells by using various concentrations of AuNPs (10 to 100 μM) for 24 h. Our findings suggest that AuNPs are non-cytotoxic and biocompatible. To the best of our knowledge, this is the first report to describe the synthesis of monodispersed, biocompatible, and soluble AuNPs with an average size of 20 nm using Ganoderma spp. This study opens up new possibilities of using an inexpensive and non-toxic mushroom extract as a reducing and stabilizing agent for the synthesis of size-controlled, large-scale, biocompatible, and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.     

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     

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.     

Selective Cytotoxicity of Complexes with N,N,N-Donor Dipodal Ligand in Tumor Cells

The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(L^D)₂]I₂∙CH₃OH (1), [CoL^D(NCS)₂] (2) and [VOL^D(NCS)₂]∙C₆H₅CH₃ (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.     

One-pot synthesis of sustained-released doxorubicin silica nanoparticles for aptamer targeted delivery to tumor cells

Site-specific delivery of drugs can significantly reduce drug toxicity and increase the therapeutic effect. Here, we report a one-pot synthesis of doxorubicin-doped silica nanoparticles (Dox/SiNPs) by using sodium fluoride (NaF) catalyzed hydrolysis of tetraethyl orthosilicate in a water-in-oil microemulsion. Through further surface chemical modification, carboxyl-terminated Dox/SiNPs (COOH-Dox/SiNPs) exhibiting high drug entrapment efficiency, strong fluorescence and long sustained release are obtained. Cell toxicity tests demonstrate that the COOH-Dox/SiNPs kill tumor cells effectively, while pure COOH-SiNPs are nontoxic. An aptamer is further conjugated to the nanoparticles for delivering loaded Dox to target cells. It is demonstrated that Dox/SiNPs modified with the aptamer sgc8c (sgc8c-Dox/SiNPs) could deliver loaded doxorubicin to CCRF-CEM cells with high specificity and excellent efficiency. Furthermore, ex vivo imaging studies show that the COOH-Dox/SiNPs are able to accumulate highly in the tumor areas, thanks to the enhanced permeability and retention (EPR) effects. Our data suggest that the sgc8c-Dox/SiNPs may be a useful new tumor therapy system.