Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Synthesis of 3-octadecanoxypropyl 6-deoxy-6-sulfo-α-d-glucopyranoside (ODSG) as a lipase-resistant SQAP derivative.

Sulfoquynovosylacyl propanediol (SQAP; 1) has been developed as a radiosensitizer (anti-cancer agent) for solid tumors, but it was easily cleaved in vivo and had a problem of short residence time. We synthesized a novel compound of a SQAP derivative (3-octadecanoxypropyl 6-deoxy-6-sulfo-α-d-glucopyranoside: ODSG; 2) to solve these problems not easily cleaved by lipase. ODSG (2) cytotoxicity was investigated in vitro, resulting in low toxicity like SQAP (1).

Hypericin-loaded oil-in-water nanoemulsion synthesized by ultrasonication process enhances photodynamic therapy efficiency.

Hypericin (Hy) is a hydrophobic photosensitizer used in photodynamic therapy for cancer therapeutic. In this study, Hy-loaded oil-in-water (O/W) nanoemulsions (NEs) were produced by the ultrasonication method combing different biocompatible oils and surfactants to enhance Hy aqueous solubility and bioavailability. Experimental parameters were optimized by the characterization of droplet size, zeta potential, and physicochemical properties. In vitro studies based on the release profile, cytotoxicity, cell morphology, and Hy intracellular accumulation were assayed. Hy at 100 mg L-1 was incorporated into the low viscosity (~0.005 Pa s) NEs with spherical droplets averaging 20-40 nm in size and polydispersity index <0.02. Hy release from the NE was significantly higher (4-fold) than its suspension (p < 0.001). The NEs demonstrated good physical stability during storage at 5 °C for at least six months. The Hy-loaded NEs exhibited an IC50 value 6-fold lower than Hy suspension during PDT against breast cancer cell lines (MCF-7). Cell microscopy imaging confirmed the increased cytotoxic effects of Hy-loaded NEs, showing damaged and apoptotic cells. Confocal laser scanning microscopy evidenced greater Hy delivery through NE into MCF-7 cells followed by improved intracellular ROS generation. Our results suggest that the Hy-loaded NEs can improve hypericin efficacy and assist Hy-PDT's preclinical development as a cancer treatment.

Macrophages mediated delivery of chlorin e6 and treatment of lung cancer by photodynamic reprogramming.

Photodynamic therapy (PDT) is an emerging anti-tumor strategy.Photosensitizer chlorin e6 (Ce6) can induce photodynamic effect to selectively damage lung cancer cells.In order to further improve its tumor targeting ability, macrophages can be applied as carrier to deliver Ce6 to lung cancer.Tumor associated macrophages (TAM) are important immunocytes in lung cancer immune microenvironment. TAM play crucial role in tumor promotion due to the Immunosuppressive property, reprogramming phenotype of TAM therefore has become a promising strategy.Based on this, in the present study, we suppose that TAM can be used as carrier to deliver Ce6 to lung cancer and be reprogrammed to M1 phenotype by photodynamic action to mediate anti-lung cancer efficacy.The results showed TAM could load with Ce6 and keep viability in the absence of near infrared irradiation (NIR).Moreover, Its viability decreased little within 10 h after NIR.Ce6-loaded TAM could deliver Ce6 to lung cancer cells and retain some drugs in TAM per se.After NIR, phagocytosis of macrophages was enhanced. The expressions of GBP5, iNOS and MHC-II was up-regulated, which indicated TAM were polarized to M1 phenotype.Finally, the study also found the reprogrammed macrophages could inhibit the proliferation and promote the apoptosis of lung cancer cells.These results suggested that macrophages could deliver Ce6 to lung cancer and exhibit anti-lung cancer effect through photodynamic reprogramming.This study provides a novel approach for combining photodynamic action with anti-tumor immunotherapy.

Induction of apoptosis, cytotoxicity and radiosensitization by novel 3,4-dihydroquinazolinone derivatives.

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC50 in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC50 values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in reference to Erlotinib (IC50 = 96.6 nM). In further studies on compounds 7, 19, 26 and 27 using HepG-2 cell line, there was significant overexpression of p21 and downregulation of two members of IAPs protein family; Survivin and XIAP, relative to their controls. Annexin V-FITC and caspase-3 analyses have established a significant increase in early apoptosis. Moreover, the four selected compounds have impaired cell proliferation by cell cycle arrest at the G2/M phase compared to their respective control. Considering radiotherapy as the primary treatment for many types of solid tumors, the radiosensitizing abilities of compounds 7, 19, 26 and 27 were measured against HepG-2 and MCF-7 cell lines combined with a single dose of 8 Gy gamma radiation. Measurement of the IC50 of the promising compounds after irradiation revealed their ability to sensitize the cells to the lethal effect of gamma irradiation (IC50 = 1.56-4.32 µM and 3.06-5.93 µM for HepG-2 and MCF-7 cells, respectively). Molecular docking was performed to gain insights into the ligand-binding interactions of 7, 19, 26 and 27 inside the EGFR binding sites and revealed their essential interactions, explaining their good activity towards EGFR.

Targeting Aurora B kinase with Tanshinone IIA suppresses tumor growth and overcomes radioresistance.

Aurora B kinase is aberrantly overexpressed in various tumors and shown to be a promising target for anti-cancer therapy. In human oral squamous cell carcinoma (OSCC), the high protein level of Aurora B is required for maintaining of malignant phenotypes, including in vitro cell growth, colony formation, and in vivo tumor development. By molecular modeling screening of 74 commercially available natural products, we identified that Tanshinone IIA (Tan IIA), as a potential Aurora B kinase inhibitor. The in silico docking study indicates that Tan IIA docks into the ATP-binding pocket of Aurora B, which is further confirmed by in vitro kinase assay, ex vivo pull-down, and ATP competitive binding assay. Tan IIA exhibited a significant anti-tumor effect on OSCC cells both in vitro and in vivo, including reduction of Aurora B and histone H3 phosphorylation, induction of G2/M cell cycle arrest, increase the population of polyploid cells, and promotion of apoptosis. The in vivo mouse model revealed that Tan IIA delayed tumor growth of OSCC cells. Tan IIA alone or in combination with radiation overcame radioresistance in OSCC xenograft tumors. Taken together, our data indicate that Tan IIA is an Aurora B kinase inhibitor with therapeutic potentials for cancer treatment.

Biological evaluation, radiosensitizing activity and structural insights of novel halogenated quinazoline-sulfonamide conjugates as selective human carbonic anhydrases IX/XII inhibitors.

A library of iodoquinazolinones endowed with benzenesulfonamide moiety was designed and synthesized as human carbonic anhydrase (hCA) inhibitors. Compounds 4-17 showed generally poor activity against the cytosolic hCA I and hCA II isoforms. Contrarily they were more potent and showed a variable spectrum of selectivity against the tumor-specific isoforms hCA IX and hCA XII. The 4-iodophenyl derivative 12 and the 4-pyridinyl derivative 15 were the most active and selective in this series against hCA IX and hCA XII isoforms with KI of 18 and 9 nM, respectively. Compounds 12 and 15 were further screened for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines besides WI38 and MCF-10A normal cell lines to determine their selectivity towards cancer cells. Compound 12 was selective towards HepG-2 and HCT-116 cell lines but less selective towards MCF-7. While compound 15 showed higher selectivity towards HepG-2 than HCT-116 and MCF-7 cell lines. The ability of compounds 12 and 15 to sensitize the cells against gamma irradiation's effect proved their potential radiosensitizing activity. Molecular docking analysis was carried out to discover the possible binding mode of the compounds within the active site of isoform hCA IX and XII. Compounds 12 and 15 revealed the probable fundamental interactions explaining the good activity and selectivity towards the tumor-specific isoforms.

Synthesis of some quinazolinones inspired from the natural alkaloid L-norephedrine as EGFR inhibitors and radiosensitizers.

A set of quinazolinones synthesized by the aid of L-norephedrine was assembled to generate novel analogues as potential anticancer and radiosensitizing agents. The new compounds were evaluated for their cytotoxic activity against MDA-MB-231, MCF-7, HepG-2, HCT-116 cancer cell lines and EGFR inhibitory activity. The most active compounds 5 and 6 were screened against MCF-10A normal cell line and displayed lower toxic effects. They proved their relative safety with high selectivity towards MDA-MB-231 breast cancer cell line. Measurement of the radiosensitizing activity for 5 and 6 revealed that they could sensitize the tumour cells after being exposed to a single dose of 8 Gy gamma radiation. Compound 5 was able to induce apoptosis and arrest the cell cycle at the G2-M phase. Molecular docking of 5 and 6 in the active site of EGFR was performed to gain insight into the binding interactions with the key amino acids.

LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy.

Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich repeat-containing protein 31 (LRRC31), that was identified through a genome-wide CRISPR screen. We found that overexpression of LRRC31 suppresses DNA repair and sensitizes BCBMs to radiation. Mechanistically, LRRC31 interacts with Ku70/Ku80 and the ataxia telangiectasia mutated and RAD3-related (ATR) at the protein level, resulting in inhibition of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) recruitment and activation, and disruption of the MutS homologue 2 (MSH2)-ATR module. We demonstrate that targeted delivery of the LRRC31 gene via nanoparticles improves the survival of tumour-bearing mice after irradiation. Collectively, our study suggests LRRC31 as a major DNA repair suppressor that can be targeted for cancer radiosensitizing therapy.

Developing a clinically relevant radiosensitizer for temozolomide-resistant gliomas.

The prognosis for patients with glioblastoma (GB) remains grim. Concurrent temozolomide (TMZ) radiation-the cornerstone of glioma control-extends the overall median survival of GB patients by only a few months over radiotherapy alone. While these survival gains could be partly attributed to radiosensitization, this benefit is greatly minimized in tumors expressing O6-methylguanine DNA methyltransferase (MGMT), which specifically reverses O6-methylguanine lesions. Theoretically, non-O6-methylguanine lesions (i.e., the N-methylpurine adducts), which represent up to 90% of TMZ-generated DNA adducts, could also contribute to radiosensitization. Unfortunately, at concentrations attainable in clinical practice, the alkylation capacity of TMZ cannot overwhelm the repair of N-methylpurine adducts to efficiently exploit these lesions. The current therapeutic application of TMZ therefore faces two main obstacles: (i) the stochastic presence of MGMT and (ii) a blunted radiosensitization potential at physiologic concentrations. To circumvent these limitations, we are developing a novel molecule called NEO212-a derivatization of TMZ generated by coupling TMZ to perillyl alcohol. Based on gas chromatography/mass spectrometry and high-performance liquid chromatography analyses, we determined that NEO212 had greater tumor cell uptake than TMZ. In mouse models, NEO212 was more efficient than TMZ at crossing the blood-brain barrier, preferentially accumulating in tumoral over normal brain tissue. Moreover, in vitro analyses with GB cell lines, including TMZ-resistant isogenic variants, revealed more potent cytotoxic and radiosensitizing activities for NEO212 at physiologic concentrations. Mechanistically, these advantages of NEO212 over TMZ could be attributed to its enhanced tumor uptake presumably leading to more extensive DNA alkylation at equivalent dosages which, ultimately, allows for N-methylpurine lesions to be better exploited for radiosensitization. This effect cannot be achieved with TMZ at clinically relevant concentrations and is independent of MGMT. Our findings establish NEO212 as a superior radiosensitizer and a potentially better alternative to TMZ for newly diagnosed GB patients, irrespective of their MGMT status.

Boosting the abscopal effect of radiotherapy: a smart antigen-capturing radiosensitizer to eradicate metastatic breast tumors.

A smart antigen-capturing radiosensitizer based on hollow mesoporous titanium dioxide (HTiO2) has been developed for metastatic breast tumor treatment.

Enzymatic transformation and anti-tumor activity of Sargassum horneri fucoidan.

Structure of the fucoidan from Sargassum horneri and products of its enzymatic transformation with molecular weight over 20 kDa were investigated. Fucoidan was hydrolyzed by recombinant fucoidanase FFA1 and its fraction of higher molecular weight was fractionated using anion-exchange chromatography, resulting in three sulphated polysaccharides of various molecular weight (63-138 kDa). Their structures were analyzed using NMR spectroscopy, showing the fucoidan (ShF) to be a branched polysaccharide with the backbone consisting of the repeating →3-α-l-Fucp(2SO3-)-1→4-α-l-Fucp(2,3SO3-)-1→ fragment and side chains including the α-l-Fucp-1→2-α-l-Fucp-1→ or α-l-Fucp-1→3-α-l-Fucp(4SO3-)-1→ fragments attached to the main chain at C4. The fragment F3 differing by molecular weight and side chain from other fucoidans fragments possessed the most significant anticancer and radiosensitizing activities.

Photofunctional Cyclometalated Iridium(III) Polypyridine Complexes Bearing a Perfluorobiphenyl Moiety for Bioconjugation, Bioimaging, and Phototherapeutic Applications.

In this article, we report the design, synthesis, and characterization of a series of cyclometalated iridium(III) polypyridine complexes containing a perfluorobiphenyl (PFBP) moiety [Ir(N^C)2(bpy-PFBP)](PF6) (bpy-PFBP = 4-(S-(perfluoro-(1,1'-biphenyl)-4-yl)-N-mercaptoethylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = 2-phenylpyridine (Hppy) (1a), 2-(4-hydroxymethylphenyl)pyridine (Hppy-CH2OH) (2a), 2-((1,1'-biphenyl)-4-yl)pyridine (Hpppy) (3a), 2-((4'-hydroxymethyl-1,1'-biphenyl)-4-yl)pyridine (Hpppy-CH2OH) (4a), 2-phenylquinoline (Hpq) (5a), 2-(4-hydroxymethylphenyl)quinoline (Hpq-CH2OH) (6a)). Their PFBP-free counterparts [Ir(N^C)2(bpy-C4)](PF6) (bpy-C4 = 4-(N-n-butylaminocarbonyloxymethyl)-4'-methyl-2,2'-bipyridine; HN^C = Hppy (1b), Hppy-CH2OH (2b), Hpppy (3b), Hpppy-CH2OH (4b), Hpq (5b), Hpq-CH2OH (6b)) were also prepared for comparison studies. Upon irradiation, all the complexes displayed intense and long-lived greenish-yellow to orange luminescence in solutions under ambient conditions and in low-temperature alcohol glass. Reactions of the PFBP complexes with peptides containing the FCPF sequence via the π-clamp-mediated cysteine conjugation afforded luminescent peptide conjugates that exhibited rich photophysical properties. Using complex 3a as an example, we demonstrated that the conjugation of complexes to organelle-targeting peptides is an effective means to modulate their intracellular localization behavior, which was further shown to be important to their performance in photodynamic therapy. The results of this work will contribute to the development of photofunctional transition metal complexes as theranostic agents.

LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells.

Radiotherapy (RT) is an important radical treatment for locally advanced non-small cell lung cancer (NSCLC). However, radioresistance greatly impairs the efficacy of this therapy in the clinic. Radioresistance can be caused by radiation-induced myeloid-derived suppressor cell (MDSC) infiltration. Liver-X nuclear receptor (LXR) agonists have demonstrated potent antitumor activity in preclinic animal models. Here, we report for the first time that LXR agonists, GW3965 and RGX-104, radiosensitized NSCLC in a subcutaneous homograft murine model. LXR activation significantly reduced MDSC abundance in the tumor microenvironment (TME). Treatment with RGX-104 greatly promoted MDSC apoptosis in vitro. Depleting MDSC activated cytotoxic T lymphocyte (CTL) and T-helper 1 (Th1) responses in the TME. In conclusion, the immunosuppressive effects of radiotherapy can be abrogated partly with an LXR agonist by depleting MDSC, which sensitizes NSCLC to RT.

DNA Strand Break Properties of Protoporphyrin IX by X-Ray Irradiation against Melanoma.

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3'-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

Improving tumor hypoxia and radiotherapy resistance via in situ nitric oxide release strategy.

Radiation therapy remains one of the main treatments for cancer. However, conventional radiotherapy not only manifests a low radiation accumulation in the tumor site, but also displays numerous negative effects. The most serious clinical problem is the radiotherapy resistance leading to cancer deterioration. As an important gaseous signal molecule, nitric oxide (NO) has been widely studied for its role in regulating angiogenesis, improving hypoxia, and inhibiting tumor growth. However, due to the unstable characteristic, the application of NO in cancer therapy is still limited. Here, we designed a micellar system formed by a NO donor, D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-NO, for enabling sustained NO release to efficiently deliver NO into the tumor area. TPGS-NO could accumulate in the tumor site for extended circulation, thereby releasing NO to exert antitumor effects and enhance radiotherapy effects under low-oxygen conditions. It demonstrated the increased sensitivity of radiotherapy through enhancing tumor angiogenesis appropriately reducing tumor area hypoxia, which significantly induced tumor cell apoptosis and inhibited its repair during radiation. This work may show great potential in synergistic radiotherapy against cancer by facile NO donor administration.

Assessment of tumour hypoxia, proliferation and glucose metabolism in head and neck cancer before and during treatment.

OBJECTIVE: The aim of the study was to assess the feasibility of multitracer positron emission tomography (PET) imaging before and during chemoradiation and to evaluate the predictive value of image-based factors for outcome in locally advanced head and neck cancers treated with chemoradiation. METHODS: In the week prior to the treatment [18F]-2-flu-2-deoxy-D-glucose (FDG), [18F]-3'-flu-3'deoxythymidine (FLT) and [18F]-flumisonidazole (FMISO) imaging was performed. FLT scans were repeated at 14 and 28 Gy and FMISO at 36 Gy. Overall survival, disease-free survival and local control were correlated with subvolume parameters, and with tumour-to-muscle ratio for FMISO. For every tracer, total metabolic tumour volume was calculated. RESULTS: 33 patients were included. No correlation was found between pre-treatment maximum standardised uptake value for FDG, FLT, FMISO and outcomes. Tumour volume measured on initial CT scans and initial FLT volume correlated with disease-free survivall (p = 0.007 and 0.04 respectively). FDG and FLT metabolic tumour volumes correlated significantly with local control (p = 0.005 and 0.02 respectively). In multivariate Cox analysis only individual initial TMRmax correlated with overall survival. CONCLUSION: PET/CT imaging is a promising tool. However, various aspects of image analysis need further clinical validation in larger multicentre study employing uniform imaging protocol and standardisation, especially for hypoxia tracer. ADVANCES IN KNOWLEDGE: Monitoring of biological features of the tumour using multitracer PET modality seems to be a feasible option in daily clinical practice.Evaluation of hypoxic subvolumes is more patient dependent; thus, exploration of individual parameters of hypoxia is needed. tumour-to-muscle ratio seems to be the most promising so far.

Platelet-membrane-camouflaged bismuth sulfide nanorods for synergistic radio-photothermal therapy against cancer.

Bismuth-containing nanoparticles (BNPs) are potential enhancers for tumor radiotherapy. Improving the bioavailability and developing synergistic therapeutic regimens benefit the drug transformation of BNPs. In the present study, we prepare a mesoporous silica-coated bismuth nanorod (BMSNR) camouflaged by a platelet membrane (PM). This biomimetic material is termed BMSNR@PM. The PM camouflage enhances the immune escape of the BMSNRs by lowering endocytosis by macrophages in the reticuloendothelial system. Additionally, the PM camouflage strengthens the material tumor-targeting capacity and leads to better radiotherapeutic efficacy compared with bare BMSNRs. Owing to the photothermal effect, BMSNR@PMs alters the cell cycle of 4T1 cancer cells post-treatment with 808 nm near-infrared irradiation (NIR). The proportions of S phase and G2/M phase cells decrease and increase, respectively, which explains the synergistic effect of NIR on BMSNR@PM-based radiotherapy. BMSNR@PMs efficiently eradicates cancer cells by the combined action of photothermal therapy (PTT) and radiotherapy in vivo and markedly improves the survival of 4T1-tumor-bearing mice. The synergistic therapeutic effect is superior to the outcomes of PTT and radiotherapy performed alone. Our study demonstrates a versatile bismuth-containing nanoplatform with tumor-targeting, immune escape, and radiosensitizing functionalities using an autologous cell membrane biomimetic concept that may promote the development of radiotherapy enhancers.

Combined Cancer Chemo-Photodynamic and Photothermal Therapy Based on ICG/PDA/TPZ-Loaded Nanoparticles.

Although photodynamic therapy (PDT) has been an attractive strategy for several cancer treatments in the clinical setting, PDT efficacy is attenuated by consumption of oxygen. To address this photodynamic issue, we adopted a phototherapy-chemotherapy combination strategy based on targeted delivery of the near-infrared photosensitizer indocyanine green (ICG), photothermal conversion agent polydopamine (PDA), and tirapazamine (TPZ), a hypoxia-activated prodrug. Under laser irradiation, ICG consumption of oxygen and aggravated hypoxia in tumor sites can activate TPZ to damage DNA. In parallel, ICG produces reactive oxygen species which work in synergy with PDA to enhance phototherapeutic efficiency. Herein, hybrid CaCO3/TPGS nanoparticles delivering ICG, PDA, and TPZ (ICG-PDA-TPZ NPs) were designed for effective and safe cancer therapy. ICG-PDA-TPZ NPs showed significantly improved cellular uptake and accumulation in tumors. Furthermore, we demonstrated that ICG-PDA-TPZ NPs showed intensive photodynamic and photothermal effects in vitro and in vivo, which synergized with TPZ in subcutaneous U87 malignant glioma growth and orthotopic B16F10 tumor inhibition, with negligible side effects. Thus, ICG-PDA-TPZ NPs could be an effective strategy for improvement of PDT.

Anti-MUC1 Aptamer as Carrier Tool of the Potential Radiosensitizer 1,10 Phenanthroline in MCF-7 Breast Cancer Cells.

BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.