DNA-based nanosized functional ruthenium(II) complex as potential phosphorescent probe to track tumor cells.

Identifying tumor cells can be challenging due to cancer's complex and heterogeneous nature. Here, an efficacious phosphorescent probe that can precisely highlight tumor cells has been created. By combining the ruthenium(II) complex with oligonucleotides, we have developed a nanosized functional ruthenium(II) complex (Ru@DNA) with dimensions ranging from 300 to 500 nm. Our research demonstrates that Ru@DNA can readily traverse biomembranes via ATP-dependent endocytosis without carriers. Notably, the nanosized ruthenium(II) complex exhibits rapid and selective accumulation within tumor cells, possibly attributed to the nanoparticles' enhanced permeation and retention (EPR) effect. Ru@DNA can also effectively discern and label the transplanted cancer cells in the zebrafish model. Moreover, Ru@DNA is efficiently absorbed into the intestine and further distributed in the pancreas. Our findings underscore the potential of Ru@DNA as a DNA-based nanodevice derived from a functional ruthenium(II) complex. This innovative nanodevice holds promise as an efficient phosphorescent probe for both in vitro and in vivo imaging of living tumor cells.

A Gold Nanocage Probe Targeting Survivin for the Diagnosis of Pancreatic Cancer.

In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur-AuNC•Gd-Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and MR imaging agents, the gold cage is an outstanding platform. Furthermore, it has the potential to transport different drugs in the future, making it a unique carrier platform. The utilization of Sur-AuNC•Gd-Cy7 nanoprobes has proven to be an effective means of targeting and localizing survivin-positive BxPC-3 cells within their cytoplasm. By targeting survivin, an antiapoptotic gene, the Sur-AuNC•Gd-Cy7 nanoprobe was able to induce pro-apoptotic effects in BxPC-3 pancreatic cancer cells. The biocompatibility of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes is evaluated through the hemolysis rate assay. The stability of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes was evaluated by determining their hydrodynamic dimensions following storage in different pH solutions for a corresponding duration. Excellent biocompatibility and stability of the Sur-AuNC•Gd-Cy7 nanoprobes will facilitate their further utilization in vivo and in vitro. The surface-bound survivin plays a role in facilitating the Sur-AuNC•Gd-Cy7 nanoprobes' ability to locate the BxPC-3 tumor. The probe was modified to incorporate Gd and Cy7, thereby enabling the simultaneous utilization of magnetic resonance imaging (MRI) and fluorescence imaging (FI) techniques. In vivo, the Sur-AuNC•Gd-Cy7 nanoprobes were found to effectively target and localize survivin-positive BxPC-3 tumors through the use of MRI and FI. After being injected via the caudal vein, the Sur-AuNC•Gd-Cy7 nanoprobes were found to accumulate effectively in an in situ pancreatic cancer model within 24 h. Furthermore, these nanoprobes were observed to be eliminated from the body through the kidneys within 72 h after a single injection. This characteristic is crucial for a diagnostic agent. Based on the aforementioned outcomes, the Sur-AuNC•Gd-Cy7 nanoprobes have significant potential advantages for the theranostic treatment of pancreatic cancer. This nanoprobe possesses distinctive characteristics, such as advanced imaging abilities and specific drug delivery, which offer the possibility of enhancing the precision of diagnosis and efficacy of treatment for this destructive illness.

Recent advances in using folate receptor 1 (FOLR1) for cancer diagnosis and treatment, with an emphasis on cancers that affect women.

A glycosylphosphatidylinositol (GPI)-anchored glycoprotein called the folate receptor 1 (FOLR1) facilitates the transportation of folate by mediating receptor-mediated endocytosis in response to ligand binding. While FOLR1 expression is typically restricted to the apical surfaces of the epithelium in the lung, kidney, and choroid plexus in healthy people, it is overexpressed in a number of solid tumours, including high-grade osteosarcoma, breast cancer, ovarian cancer, and non-small cell lung cancer. As a result, FOLR1 has become an attractive target for cancer detection and therapy, particularly for cancers that affect women. A number of methods have been developed to target FOLR1 in cancer therapy, including the development of FOLR1-targeted imaging agents for cancer diagnosis and the use of folate conjugates to deliver cytotoxic agents to cancer cells that overexpress FOLR1. Therefore, we focus on the most recent developments in employing FOLR1 for cancer diagnosis and treatment in this review, particularly with regard to cancers that affect women.

Fast detection, a precise and sensitive diagnostic agent for breast cancer.

BACKGROUND: Breast cancer targeting diagnostic agent with effective imaging ability is important in guiding plan formulation, prediction, and curative effect evaluation of tumors in clinic. A tumor-targeting nanoprobe based on the functional and programmable Liquid-Liquid phase separation of AS1411 promoted by Ru(II) complex RuPEP may develop into a potential phosphorescence probe to detect breast cancer cells, where AS1411 act as a tumor-targeting guidance moiety to distinguish tumor cells from normal cells and RuPEP act as a light-emitting element to highlight breast cancer cells. METHODS: Here we designed and constructed a nanoprobe AS1411@RuPEP, and the physicochemical and biochemical properties were characterized by TEM, AFM and EDS. The breast cancer targeting diagnostic capacity was evaluated by normal/tumor cell co-culture assay, tumor cells targeting tracking in xenograft model and cancerous area selectively distinguishing in human patient tissue. RESULTS: Further studies indicated that the nanoprobe exhibits excellent tumor-targeting imaging ability in vitro and in vivo by effectively recognize the over-expressed nucleolin (NCL) on the breast cancer cells membrane. Intriguingly, we discovered that the selectively enrichment of nanoprobe particles in tumor cells is related to ATP-dependent NCL transport processes that rely on the AS1411 component of nanoprobe to recognize NCL. Furthermore, preferential accumulation of nanoprobe is clearly differentiating the human breast cancer tissue surrounding non-cancerous tissue in histological analysis. CONCLUSION: This study produce a potent nanoprobe can be used as a convenient tool to highlight and distinguish tumor cells in vivo, and indicate the tumorous grading and staging in human breast cancer patient pathological section, which provides an effective way for breast cancer diagnostic imaging by targeting recognize NCL.

Noninvasively visualize the expression of LAPTM4B protein using a novel 18F-labeled peptide PET probe in hepatocellular carcinoma.

OBJECTIVE: Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. METHODS: A PET targeting tracer named [18F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Radio-stability, cell uptake, micro PET/CT imaging and ex vivo biodistribution were performed for determining its stability, cell binding specificity, and tumor targeting in vivo. RESULTS: [18F]FP-LAP2H was successfully synthesized with radiochemical yields of 6-14% (decay-corrected yield) and molar activity of 10-44 GBq/µmol. The tracer showed stable (~90%) in phosphate-buffered saline, pH 7.4, and in human serum (~80%) for 2 h. In vitro cell uptake studies indicated the radioactivity accumulation in HCC cells was LAPTM4B protein-specific. Micro PET/CT demonstrated that implanted LAPTM4B positive HepG2 and BEL7402 tumors could be clearly visualized. The ex vivo biodistribution studies demonstrated that the tumor/liver ratio were 1.80 ± 0.65 and 2.09 ± 0.68 in implanted HepG2 and BEL7402 tumors respectively. Negative control and blocking experiments revealed that the radioactivity uptake in the HCC tumor was LAPTM4B protein-specific. CONCLUSIONS: [18F]FP-LAP2H appears to be a potential PET tracer for imaging LAPTM4B-positive HCC tumor. Further endeavors need to do to improve tumor/liver ratio.

Carbon Dots as an Indicator of Acid-Base Titration and a Fluorescent Probe for Endoplasm Reticulum Imaging.

In this study, carbon dots (CDs) with red color are successfully prepared via hydrothermal treatment of o-phenylenediamine and urea. The as-prepared red CDs exhibit an acidichromism feature, making them turn purple at pH 4.4 and become blue at pH 3.3. Further investigations reveal that the surface chemical bond species of CDs are responsible for the acidichromism feature. Taking advantage of the acidichromism feature, the CDs are employed as a titration indicator for analysis of alkali samples, which gives rise to satisfactory results without significant difference between the titration methods using CDs and methyl orange or a mixture of methyl red and bromocresol green as indicators. The CDs show excitation-independent fluorescence with dual-emission at 600 and 650 nm, along with a respectable quantum yield of 20.1%, which provides the CDs with deep tissue penetration and minimum autofluorescence background that is desirable in bioimaging. In addition, the CDs are found to light up endoplasm reticulum particularly, indicating their endoplasm reticulum targeting capability, which is proven by a colocalization study with other classical subcellular dyes. Endocytosis inhibiting investigations confirm that the endoplasm reticulum targeting ability is mainly attributed to the caveolin/lipid-raft-mediated endocytosis pathways of CDs. This study not only presents a facile approach for red CDs but also explores the possibility of CDs in titration analysis and in endoplasm reticulum targeting imaging.

Dosimetry of tumor targeting imaging by convergent X-ray beam as compared with nuclear medicine.

During decades nuclear medicine procedures, based on radiolabeled agents, have proved to be efficient for diseases diagnosis and treatment. Radiation emerging from patient is detected aimed at localizing radiotracer distribution that is further correlated with biochemical/metabolic physiological processes. However, a significant drawback associated with current nuclear medicine procedures implementing radionuclide infusion regards to the inherent absorbed dose as well as radiopharmaceuticals' production, storage and elimination from patient body, thus representing a risk at patient and public health level. In the recent years, alternative methods have been proposed to reduce/eliminate radionuclides in some nuclear medicine procedures. The combination of high atomic number nanoparticles infused within patient body with incident X-ray beam, like tumor targeting and treatment, appears as a potential alternative method capable of theranostics. The process is based on inducing X-ray fluorescence and secondary electrons emission in high atomic number nanoparticles by means of excitation with an external X-ray beam, avoiding employing radioactive substances. The present work reports on the dosimetry performance of both methods, comparing whenever the external convergent X-ray beam alternative may involve less or larger radiation dose levels, according to comparable signal/image quality during the procedure. To this aim, a simplified theoretical model is proposed and associated Monte Carlo simulations are performed in order to compare typical case of nuclear medicine imaging with potential performance of an innovative method, called OXIRIS (Orthovoltage X-ray Induced Radiation and Integrated System), based on convergent X-ray beam exciting high atomic number nanoparticles infused in patient. The obtained results support the proposed alternative method's feasibility, once demonstrated that patient absorbed dose levels are relative similar to those currently used by nuclear medicine procedures, whereas dose to targeted region (tumor) are significantly higher, which may be useful for treatment purposes.

Dual-Mode Contrast Agents with RGD-Modified Polymer for Tumour-Targeted US/NIRF Imaging.

BACKGROUND: Cancer diagnosis and treatment during the early stages of disease remain extremely challenging clinical tasks. The development of effective multimode contrast agents could greatly facilitate the early detection of cancer. MATERIALS AND METHODS: We prepared dual-mode contrast agents using a biotin/avidin bioamplification system. Through in vivo and in vitro experiments, we verified the imaging performance of this contrast agents in both fluorescence and ultrasound and its targeting specificity for MDA-MB-231 cells. RESULTS: The RGD peptide-labelled microbubbles showed excellent targeting of αvß3 integrin expressed by MDA-MB-231 cells in vitro and in vivo. The signal intensity and time duration of ultrasound imaging using these particles were superior to those obtained with a typical ultrasound contrast agent in the clinic. The tumour areas also demonstrated high Cy5.5 accumulation by fluorescence imaging. CONCLUSION: The results show that this targeted dual-mode imaging system yields outstanding US/NIRF imaging results, possibly allowing the early clinical diagnosis of cancer.

One-for-All Nanoplatform for Synergistic Mild Cascade-Potentiated Ultrasound Therapy Induced with Targeting Imaging-Guided Photothermal Therapy.

Ameliorated therapy based on the tumor microenvironment is becoming increasingly popular, yet only a few methods have achieved wide recognition. Herein, targeting multifunctional hydrophilic nanomicelles, AgBiS2@DSPE-PEG2000-FA (ABS-FA), were obtained and employed for tumor treatment. In a cascade amplification mode, ABS-FA exhibited favorable properties of actively enhancing computed tomography/infrared (CT/IR) imaging and gently relieving ambient oxygen concentration by cooperative photothermal and sonodynamic therapy. Compared with traditional Bi2S3 nanoparticles, the CT imaging capability of the probe was augmented (43.21%), and the photothermal conversion efficiency was increased (33.1%). Furthermore, remarkable ultrasonic dynamic features of ABS-FA were observed, with increased generation of reactive oxygen species (24.3%) being obtained compared to Ce6, a commonly used sonosensitizer. Furthermore, ABS-FA exhibited obvious inhibitory effects on HeLa cell migration at 6 µg/mL, which to some extent, demonstrated its suppressive effect on tumor growth. A lower dose, laser and ultrasonic power, and shorter processing time endowed ABS-FA with excellent photothermal and sonodynamic effects. By mild cascade mode, the hypoxic condition of the tumor site was largely improved, and a suitable oxygen-rich environment was provided, thereby endowing ABS-FA with a superior synergistically enhanced treatment effect compared with the single-mode approach, which ultimately realized the purpose of "one injection, multiple treatment". Moreover, our data showed that ABS-FA was given with a biological safety profile while harnessing in vivo. Taken together, as a synergistically enhanced medical diagnosis and treatment method, the one-for-all nanoplatform will pave a new avenue for further clinical applications.

Enhancing the magnetic relaxivity of MRI contrast agents via the localized superacid microenvironment of graphene quantum dots.

The design of contrast agents (CAs) with high magnetic relaxivities is a key issue in the field of magnetic resonance imaging (MRI). The traditional strategy employed is aimed at optimizing the structural design of the magnetic atoms in the CA. However, it is difficult to obtain an agent with magnetic relaxivity over 100 mM-1 s-1 using this approach. In this work, we demonstrate that modulation of the localized superacid microenvironment of certain CAs (Gd3+ loaded polyethylene glycol modified graphene oxide quantum dots or 'GPG' for short) can effectively enhance the longitudinal magnetic relaxivities (r1) by accelerating proton exchange. r1 values of a series of GPGs are significantly increased by 20-30 folds compared to commercially available CAs over a wide range of static magnetic field strengths (e.g. 210.9 mM-1 s-1vs. 12.3 mM-1 s-1 at 114 µT, 127.0 mM-1 s-1vs. 4.9 mM-1 s-1 at 7.0 T). GPG aided MRI images is then acquired both in vitro and in vivo with low biotoxicities. Furthermore, folic-acid-modified GPG is demonstrated suitable for MRI-fluorescence dual-modal tumor targeting imaging in animals with more than 98.3% specific cellular uptake rate.

Geometrical Confinement of Gadolinium Oxide Nanoparticles in Poly(ethylene glycol)/Arginylglycylaspartic Acid-Modified Mesoporous Carbon Nanospheres as an Enhanced T1 Magnetic Resonance Imaging Contrast Agent.

A new strategy for designing contrast agents (CAs) based on geometrical confinement will become a competent way to improve the relaxivity of CAs. Herein, a magnetic resonance imaging (MRI) nanoconstruct is fabricated through loading Gd2O3 nanoparticles into mesoporous carbon nanospheres, followed by conjugation of poly(ethylene glycol) (PEG) and the c(RGDyK) peptide (Gd2O3@OMCN-PEG-RGD), which could prolong the blood circulation half-life as well as improve the tumor-targeting ability. As a result, the Gd2O3@OMCN-PEG-RGD exhibits an outstandingly high relaxivity ( r1 = 68.02 mM-1 s-1), which is ∼5.3 times higher than that of Gd2O3 nanoparticles ( r1 = 12.74 mM-1 s-1). Afterward, both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test and H&E staining show that the Gd2O3@OMCN-PEG-RGD has wonderful biocompatibility in vitro and in vivo. Moreover, the in vivo MR images indicate that the Gd2O3@OMCN-PEG-RGD could accumulate in the tumor region more rapidly than Gd2O3@OMCN-PEG. This study presents a facile method to fabricate an MRI CA with excellent T1 contrast ability based on geometrical confinement and excellent biocompatibility, which could act as an optimal contender for sensitive in vivo tumor imaging with outstanding targeting ability.

In vivo MR imaging of folate-receptor expression with the folate-specific nanospheres in a C6 glioblastoma model.

PURPOSE: To assess the ability of magnetic albumin nanospheres conjugated with folate (FA-MAN) to provide FR-specific enhancement of C6 glioblastoma on magnetic resonance (MR) images. PROCEDURES: Active targeting effect of magnetic albumin nanospheres conjugated with folate (FA-MAN) was evaluated based on MR images and histopathological analysis. MR imaging of subcutaneously transplanted C6 glioblastomas was performed after intravenous injection of FA-MAN, non-targeted (magnetic albumin nanospheres, MAN) and FA-inhibited (magnetic albumin nanospheres conjugated with folate plus folate, FA-MAN + FA) agents at designated time points. The T2 relaxation times in tumors were compared among different treatment groups and were correlated with histopathological findings. Prussian blue staining and in vivo toxicology assay were also performed simultaneously. RESULTS: Upon MR imaging in vivo, T2 relaxation time of the tumor sites in the group administrated with FA-MAN (T2 is 49 ms, 46 ms and 45 ms at 24 h, 48 h and 72 h, respectively) has statistical difference compared to those in the groups of MAN (T2 is 56 ms, 56 ms and 61 ms at 24 h, 48 h and 72 h, respectively) and FA-MAN + FA nanospheres (T2 is 56 ms, 57 ms and 56 ms at 24 h, 48 h and 72 h, respectively). Prussian blue-stained results demonstrated that more iron particles accumulated in the tumors of the targeted group than those of the other groups. Toxicology assay showed that no noticeable body weight losses were observed after monitoring 31 days, and the results of routine blood parameters, liver and kidney function biomarkers also demonstrated that the nanoshperes did not influence the respectively physiological index. Besides, no obvious pathological injuries on the major organs were examined. CONCLUSION: Folate-conjugated magnetic albumin nanospheres were more effective in targeting C6 glioblastoma in vivo.

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes.

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well.

Preparation of anti-EGFR-PEG-SPIO molecular probe and its targeting MRI for lung adenocarcinoma cells / 中国医学影像技术

Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR),as well as the feasibility for surveillance of tumor targeting with MRI.Methods Nanoparticles (NPs)of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared,and the morphology of nanoparticles was observed with transmission electron microscope (TEM).The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI.MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro.The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM.Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI,decreased significantly compared with PEG-SPIO.The rate of signal intensity change was -58.2％,-82.7％,-94.4％ and-98.3％,respectively,at iron concentrations of (0,10,20,40,80 μg/ml) of antiEGFR-PEG-SPIO.Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells,but few of PEG-SPIO.Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro,and the targeting delivery process could be monitored with 3.0T MRI.

Synergistic Effect of Human Serum Albumin and Fullerene on Gd-DO3A for Tumor-Targeting Imaging.

A macromolecular magnetic resonance imaging (MRI) contrast agent was successfully synthesized by conjugating the gadolinium/1,4,7,10-tetraazacyclododecane-1,4,7-tetracetic acid complex (Gd-DO3A) with 6,6-phenyl-C61 butyric acid (PC61BA) and upon further modification with human serum albumin (HSA). The final product, PC61BA-(Gd-DO3A)/HSA, has a high stability and exhibits a much higher relaxivity (r1 = 89.1 mM(-1) s(-1) at 0.5 T, 300 K) than Gd-DO3A (r1 = 4.7 mM(-1) s(-1)) does under the same condition, producing the synergistic positive effect of HSA and C60 on the relaxivity of Gd-DO3A. The in vivo MR images of PC61BA-(Gd-DO3A)/HSA-treated tumor-bearing mice show strong signal enhancement for the tumor area due to the enhanced permeability and retention effect. The maximum accumulation of PC61BA-(Gd-DO3A)/HSA at the tumor site was achieved at 4 h postinjection, which may guide surgery. The results from the hematology and histological observations indicate that PC61BA-(Gd-DO3A)/HSA has no obvious toxicity in vivo. These unique properties of PC61BA-(Gd-DO3A)/HSA enable them to be highly efficient for tumor-targeting MRI in vivo, possibly providing a good solution for tumor diagnosis.

An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer.

Epithelial cell adhesion molecule (EpCAM) is known to be overexpressed in epithelial cancers associated with enhanced malignant potential, particularly colorectal carcinoma (CRC) and head and neck squamous cell carcinoma (HNSCC). However, it is unknown whether progression of malignance can be directly inhibited by targeting EpCAM. Here, we have generated five novel monoclonal antibodies (mAbs) against EpCAM. One of these anti-EpCAM mAbs, EpAb2-6, was found to induce cancer cell apoptosis in vitro, inhibit tumor growth, and prolong the overall survival of both a pancreatic cancer metastatic mouse model and mice with human colon carcinoma xenografts. EpAb2-6 also increases the therapeutic efficacy of irinotecan, fluorouracil, and leucovorin (IFL) therapy in a colon cancer animal model and gemcitabine therapy in a pancreatic cancer animal model. Furthermore, EpAb2-6, which binds to positions Y95 and D96 of the EGF-II/TY domain of EpCAM, inhibits production of EpICD, thereby decreasing its translocation and subsequent signal activation. Collectively, our results indicate that the novel anti-EpCAM mAb can potentially be used for cancer-targeted therapy.

Synthesis of dual-functional targeting probes for cancer theranostics based on iron oxide nanoparticles coated by centipede-like polymer connected with pH-responsive anticancer drug.

A tumor-targeted and pH-responsive drug release system based on superparamagnetic iron oxide nanoparticles (IONPs) coated by poly(ethylene glycol) (PEG) and dodecylamine (DDA)-modified polyitaconic acid (PIA) connecting with bortezomib (BTZ) (PIA-PEG-DDA-BTZ@IOs) has been constructed and characterized. The anticancer drug BTZ was first conjugated using dopamine as the linker via catechol borate ester bond, which is acid cleavable and used as an ideal pH-responsive drug release system. The IONPs were then coated by PIA-PEG-DDA-BTZ to form micelles with good biocompatibility. The conjugates were further designed to target liver cancer cells overexpressing vascular endothelial growth factor (VEGF) by the targeting molecule anti-vascular endothelial growth factor (anti-VEGF). The magnetic resonance imaging showed that the targeting capability of IONPs-anti-VEGF conjugates to Hep G2 cells was more significant than that of non-anti-VEGF IONPs. From the above, this kind of novel dual-functional targeting probe could provide a new idea for the diagnosis and treatment of cancer.

Distinguish cancer cells based on targeting turn-on fluorescence imaging by folate functionalized green emitting carbon dots.

Developing efficient methods for visual detection of cancer cells has the potential to contribute greatly to basic biological research and early diagnosis of cancer. Here, we report facile and one-step synthesis of green fluorescence carbon dots (CDs) with the help of a new passivating agent--poly(acrylate sodium) (PAAS). Based on the as-prepared CDs, a novel turn-on fluorescence probe was designed for targeting imaging of cancer cells via hydrogen-bond interaction between folic acid and CDs (FA-CDs). Intracellular experiments indicated that FA-CDs probe could accurately distinguish folate receptor (FR)-positive cancer cells in different cell mixtures with turn-on mode. In particular, combining the targeting of FA-CDs probe with the excellent photostability of CDs has inestimable meaning for fluorescence-assisted surgical resection and acquisition real-time information about tumor cells. Obviously, the as-prepared FA-CDs probe may have great potential as a high-performance platform for accurately recognizing special cancer cells, which may provide new tools for cancer prognosis and therapy.

Assessment of α-fetoprotein targeted HSV1-tk expression in hepatocellular carcinoma with in vivo imaging.

Tumor-specific enhancer/promoter is applicable for targeting gene expression in tumors and helpful for tumor-targeting imaging and therapy. We aimed to acquire α-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) specific images using adenovirus containing HSV1-tk gene controlled by AFP enhancer/promoter and evaluate in vivo ganciclovir (GCV)-medicated therapeutic effects on AFP-targeted HSV1-tk expression with (18)F-FDG positron emission tomography (PET). Recombinant adenovirus expressing HSV1-tk under AFP enhancer/promoter was produced (AdAFP-TK) and the expression levels were evaluated by RT-PCR and (125)I-IVDU uptake. GCV-mediated HSV1-tk cytotoxicity was determined by MTT assay. After the mixture of AdAFP-fLuc and AdAFP-TK was administrated, bioluminescent images (BLIs) and (18)F-FHBG PET images were obtained in tumor-bearing mice. In vivo therapeutic effects of AdAFP-TK and GCV in the HuH-7 xenograft model were monitored by (18)F-FDG PET. When infected with AdAFP-TK, cell viability in HuH-7 was reduced, but those in HT-29 and SK-Hep-1 were not significantly decreased at any GCV concentration less than 100 µM. AFP-targeted fLuc and HSV1-tk expression were clearly visualized by BLI and (18)F-FHBG PET images in AFP-producing HCC, respectively. In vivo GCV-mediated tumor growth inhibition by AFP-targeted HSV1-tk expression was monitored by (18)F-FDG PET. Recombinant AdAFP-TK could be applied for AFP-targeted HCC gene therapy and imaging in AFP-producing HCC.

Nanocomoposite probes composed of fluorescent magnetic nanoparticles and PSA ScFv antibody for targeted imaging and therapy of prostate cancer / 中国肿瘤生物治疗杂志

Objective:To investigate the feasibility of targeted imaging and therapy of prostate cancer using nanocomposite probes composed of fluorescent magnetic nanoparticles(FMCNPs) and single chain Fv(ScFv) antibody specific for gama-seminoprotein.Methods:The nanocomposite probes(FMCNPs-ScFv) were prepared by conjugating fluorescent magnetic nanoparticles with singlegama-chain Fv antibody specific gama-seminoprotein,and were characterized by high resolution transmission electron microscopy,fluorescent spectrum and magnetic spectrum.Nanocomposite probes were incubated with prostate cancer LNCaP cells,and the targeting results of nanocomposite probes were observed by fluorescent microscopy.The cytotoxicity effect of the nanocomposite probes was measured by MTT.Nude mice models of prostate cancer were established and identified by immunohistochemistry method.The nanocomposite probes were injected into nude mice via tail vein.The distribution of nanocomposite probes in the nude mice was observed by Micro-animal imaging system,targeted imaging of the prostate cancer was observed by MR instrument.The nude mice with prostate cancer were irradiated with 100 W magnetic field for 30 min,and the changes of tumor sizes were observed.Results:The FMCNPs-ScFv nanocomposite probes were successfully prepared.Nanocomposite probes entered into the cytoplasm of cancer cells and exhibited low cytotoxicity effect.Nude mice model with prostate cancer were successfully fabricated;the nanocomposite probes distributed quickly in the main organs of mice,and gradually concentrated on the tumor tissues within 24 h.MR images showed that the tumor images were gradually enhanced from 6 h to 24 h after injection of the nanocomposite probe.Four days after magnetic irradiation,the tumors in the nude mice grew slower compared with the control nude mice(P