Synthesis and Characterization of Sulfonamide-Containing Naphthalimides as Fluorescent Probes.

A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors.

Self-Delivery Nanoplatform Based on Amphiphilic Apoptosis Peptide for Precise Mitochondria-Targeting Photothermal Therapy.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Advances of Photothermal Agents with Fluorescence Imaging/Enhancement Ability in the Field of Photothermal Therapy and Diagnosis.

Photothermal therapy (PTT) is an effective cancer treatment method. Due to its easy focusing and tunability of the irradiation light, direct and accurate local treatment can be performed in a noninvasive manner by PTT. This treatment strategy requires the use of photothermal agents to convert light energy into heat energy, thereby achieving local heating and triggering biochemical processes to kill tumor cells. As a key factor in PTT, the photothermal conversion ability of photothermal agents directly determines the efficacy of PTT. In addition, photothermal agents generally have photothermal imaging (PTI) and photoacoustic imaging (PAI) functions, which can not only guide the optimization of irradiation conditions but also achieve the integration of disease diagnosis. If the photothermal agents have function of fluorescence imaging (FLI) or fluorescence enhancement, they can not only further improve the accuracy in disease diagnosis but also accurately determine the tumor location through multimodal imaging for corresponding treatment. In this paper, we summarize recent advances in photothermal agents with FLI or fluorescence enhancement functions for PTT and tumor diagnosis. According to the different recognition sites, the application of specific targeting photothermal agents is introduced. Finally, limitations and challenges of photothermal agents with fluorescence imaging/enhancement in the field of PTT and tumor diagnosis are prospected.

Rapidly degradable konjac glucomannan hydrogels cross-linked with olsalazine for colonic drug release.

BACKGROUND: Polysaccharide hydrogel is one of the most important materials for the colon target drug release system. However, the degradation time of polysaccharide hydrogel is much longer than the retention time in the colon. The drugs are expelled from the body before being released. OBJECTIVE: In order to match the degradation of drug carriers and their retention time in the colon, a rapidly degradable konjac glucomannan (KGM) hydrogel was designed for colon target drug release. METHODS: A crosslinker containing azo bond, olsalazine, was used to prepare the rapidly degradable KGM hydrogel. The degradation and drug release of the hydrogels with different crosslinking densities in the normal buffer and the human fecal medium were studied to evaluate the efficiency of colon drug release. RESULTS: More than 50% of the KGM hydrogel by weight was degraded and more than 60% of the 5-fluorouracil (5-Fu) was released within 48 h in 5% w/v human fecal medium. CONCLUSION: The drug was released more rapidly in a simulated colon environment than in a normal buffer. Furthermore, the drug release was controlled by the degradation of the hydrogel. The KGM hydrogel containing azo crosslinker has great potential for colon drug release.

Nucleus-Targeting Nanoplatform Based on Dendritic Peptide for Precise Photothermal Therapy.

Photothermal therapy directly acting on the nucleus is a potential anti-tumor treatment with higher killing efficiency. However, in practical applications, it is often difficult to achieve precise nuclear photothermal therapy because agents are difficult to accurately anchor to the nucleus. Therefore, it is urgent to develop a nanoheater that can accurately locate the nucleus. Here, we designed an amphiphilic arginine-rich dendritic peptide (RDP) with the sequence CRRK(RRCG(Fmoc))2, and prepared a nucleus-targeting nanoplatform RDP/I by encapsulating the photothermal agent IR780 in RDP for precise photothermal therapy of the tumor nucleus. The hydrophobic group Fmoc of the dendritic peptide provides strong hydrophobic force to firmly encapsulate IR780, which improves the solubility and stability of IR780. Moreover, the arginine-rich structure facilitates cellular uptake of RDP/I and endows it with the ability to quickly anchor to the nucleus. The nucleus-targeting nanoplatform RDP/I showed efficient nuclear enrichment ability and a significant tumor inhibition effect.

3D-Printed scaffolds based on poly(Trimethylene carbonate), poly(ε-Caprolactone), and ß-Tricalcium phosphate.

Three-dimensional (3D)-printed scaffolds of biodegradable polymers have been increasingly applied in bone repair and regeneration, which helps avoid the second surgery. PTMC/PCL/TCP composites were made using poly(trimethylene carbonate), poly(ε-caprolactone), and ß-tricalcium phosphate. PTMC/PCL/TCP scaffolds were manufactured using a biological 3D printing technique. Furthermore, the properties of PTMC/PCL/TCP scaffolds, such as biodegradation, mechanic properties, drug release, cell cytotoxicity, cell proliferation, and bone repairing capacity, were evaluated. We showed that PTMC/PCL/TCP scaffolds had low cytotoxicity and good biocompatibility, and they also enhanced the proliferation of osteoblast MC3T3-E1 and rBMSC cell lines, which demonstrated improved adhesion, penetration, and proliferation. Moreover, PTMC/PCL/TCP scaffolds can enhance bone induction and regeneration, indicating that they can be used to repair bone defects in vivo.

Dextran Fluorescent Probes Containing Sulfadiazine and Rhodamine B Groups.

Fluorescent imaging has been expanded, as a non-invasive diagnostic modality for cancers, in recent years. Fluorescent probes in the near-infrared window can provide high sensitivity, resolution, and signal-to-noise ratio, without the use of ionizing radiation. Some fluorescent compounds with low molecular weight, such as rhodamine B (RhB) and indocyanine green (ICG), have been used in fluorescent imaging to improve imaging contrast and sensitivity; however, since these probes are excreted from the body quickly, they possess significant restrictions for imaging. To find a potential solution to this, this work investigated the synthesis and properties of novel macromolecular fluorescent compounds. Herein, water-soluble dextran fluorescent compounds (SD-Dextran-RhB) were prepared by the attachment of RhB and sulfadiazine (SD) derivatives to dextran carrier. These fluorescent compounds were then characterized through IR, 1H NMR, 13C NMR, UV, GPC, and other methods. Assays of their cellular uptake and cell cytotoxicity and fluorescent imaging were also performed. Through this study, it was found that SD-Dextran-RhB is sensitive to acidic conditions and possesses low cell cytotoxicities compared to normal 293 cells and HepG2 and HeLa tumor cells. Moreover, SD-Dextran-RhB demonstrated good fluorescent imaging in HepG2 and HeLa cells. Therefore, SD-Dextran-RhB is suitable to be potentially applied as a probe in the fluorescent imaging of tumors.

Dual-modal polypeptide-containing contrast agents for magnetic resonance/fluorescence imaging.

Dual-modal magnetic resonance/fluorescent imaging (MRI/FI) attracts moreandmoreattentions in diagnosis of tumors. A corresponding dual-modal imaging agent with sufficient tumor sensitivity and specificity should be matched to improve imaging quality. Tripeptide (RGD) and pentapeptide (YIGSR) were selected as the tumor-targeting groups and attached to gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and rhodamine B (RhB), and then make two novel polypeptide-based derivatives (RGD-Gd-DTPA-RhB and YIGSR-Gd-DTPA-RhB), respectively. These derivatives were further characterized and their properties, such as cell uptake, cell cytotoxicity, MRI and FI assay, were measured. YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB had high relaxivity, good tumor-targeting property, low cell cytotoxicity and good red FI in B16F10 melanoma cells. Moreover, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB possessed high uptake to B16F10 melanoma, and then achieve highly enhanced FI and MRI of tumors in mice for a prolonged time. Therefore, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB can be applied as the potential agents for tumor targeted MRI/FI in vivo.

Biodegradable 3D Printed Scaffolds of Modified Poly (Trimethylene Carbonate) Composite Materials with Poly (L-Lactic Acid) and Hydroxyapatite for Bone Regeneration.

Biodegradable scaffolds based on biomedical polymeric materials have attracted wide interest in bone transplantation for clinical treatment for bone defects without a second operation. The composite materials of poly(trimethylene carbonate), poly(L-lactic acid), and hydroxyapatite (PTMC/PLA/HA and PTMC/HA) were prepared by the modification and blending of PTMC with PLA and HA, respectively. The PTMC/PLA/HA and PTMC/HA scaffolds were further prepared by additive manufacturing using the biological 3D printing method using the PTMC/PLA/HA and PTMC/HA composite materials, respectively. These scaffolds were also characterized by Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), automatic contact-angle, scanning electronic micrographs (SEM), diffraction of X-rays (XRD), differential scanning calorimetry (DSC), and thermogravimetry (TG). Subsequently, their properties, such as mechanical, biodegradation, cell cytotoxicity, cell compatibility in vitro, and proliferation/differentiation assay in vivo, were also investigated. Experiment results indicated that PTMC/PLA/HA and PTMC/HA scaffolds possessed low toxicity, good biodegradability, and good biocompatibility and then enhanced the cell multiplication ability of osteoblast cells (MC3T3-E1). Moreover, PTMC/PLA/HA and PTMC/HA scaffolds enhanced the adhesion and proliferation of MC3T3-E1 cells and enabled the bone cell proliferation and induction of bone tissue formation. Therefore, these composite materials can be used as potential biomaterials for bone repatriation and tissue engineering.

Cationic Peptide-Modified Gold Nanostars as Efficient Delivery Platform for RNA Interference Antitumor Therapy.

siRNA interference therapy can silence tumor cell target genes and specifically regulate tumor cell behavior and function, which is an effective antitumor therapy. However, in somatic circulation, naked siRNAs are not only susceptible to degrade, but it is also difficult to realize the tumor cells' internalization. Therefore, novel siRNA delivery vectors that could promote efficacy need to be developed urgently. Here, we designed high-surface gold nanostars (GNS-P) which are decorated with cationic tumor-targeting peptide as an efficient and functional siRNA delivery nanoplatform for tumor therapy. The positively charged amino acid sequence and huge surface area enabled the vector to load a large amount of siRNA, while the tumor-targeting peptide sequence and nano size enabled it to rapidly and precisely target the tumor regions for fast and effective siRNA delivery. This tumor-targeting nanoplatform, GNS-P, displayed good biocompatibility, low toxicity and an extraordinary tumor accumulation capability.

An europium(III) metal-organic framework as a multi-responsive luminescent sensor for highly sensitive and selective detection of 4-nitrophenol and I- and Fe3+ ions in water.

A luminescence sensor based on an europium(III)-based lanthanide-organic framework, [Eu(BCB)(DMF)]·(DMF)1.5(H2O)2 (1), was synthesized via a solvothermal method using 4,4',4''-benzenetricarbonyltribenzoic acid (H3BCB) as a bridging ligand. Single-crystal X-ray diffraction indicates that Eu centers are eight-coordinated with a trigonal dodecahedron and a square antiprismatic configuration, and adjacent Eu atoms are bridged by BCB organic linkers to form a 3D rod-packing structure. Photoluminescence studies show that compound 1 emits bright red luminescence and behaves as a multi-responsive luminescent sensor toward 4-nitrophenol (4-NP) and I- and Fe3+ ions in water with high sensitivity, selectivity and low detection limits. Furthermore, the possible luminescence sensing mechanisms were also investigated by PXRD analysis, UV-vis spectroscopy and X-ray photoelectron spectroscopy (XPS). The recognition mechanism for 4-NP and I- ions can be attributed to the competition absorption and that for Fe3+ ions is considered to be a multi-quenching mechanism dominated by competition absorption. This study demonstrates that the lanthanide-based MOF might be a promising candidate for the detection of 4-NP and I- and Fe3+ ions in aqueous medium.

3D Printed Multi-Functional Scaffolds Based on Poly(ε-Caprolactone) and Hydroxyapatite Composites.

3D Printed biodegradable polymeric scaffolds are critical to repair a bone defect, which can provide the individual porous and network microenvironments for cell attachment and bone tissue regeneration. Biodegradable PCL/HA composites were prepared with the blending of poly(ε-caprolactone) (PCL) and hydroxyapatite nanoparticles (HA). Subsequently, the PCL/HA scaffolds were produced by the melting deposition-forming method using PCL/HA composites as the raw materials in this work. Through a serial of in vitro assessments, it was found that the PCL/HA composites possessed good biodegradability, low cell cytotoxicity, and good biocompatibility, which can improve the cell proliferation of osteoblast cells MC3T3-E1. Meanwhile, in vivo experiments were carried out for the rats with skull defects and rabbits with bone defects. It was observed that the PCL/HA scaffolds allowed the adhesion and penetration of bone cells, which enabled the growth of bone cells and bone tissue regeneration. With a composite design to load an anticancer drug (doxorubicin, DOX) and achieve sustained drug release performance, the multifunctional 3D printed PCL/HA/DOX scaffolds can enhance bone repair and be expected to inhibit probably the tumor cells after malignant bone tumor resection. Therefore, this work signifies that PCL/HA composites can be used as the potential biodegradable scaffolds for bone repairing.

Polypeptide-rhodamine B probes containing laminin/fibronectin receptor-targeting sequence (YIGSR/RGD) for fluorescent imaging in cancers.

Currently, fluorescent imaging is one of the most promising diagnostic approaches for facile detection of cancers in situ in thanks to a fluorescent probe. Two novel polypeptide-based fluorescent probes for different biomarkers to cancers are reported here. These probes focused on tyrosine-isoleucine-glycine-serine-arginine (YIGSR) and arginine-glycine-aspartic (RGD), which receptors play an important role in the extracellular matrix and are overexpressed in tumor cells and then can be used as tumor-targeting groups in fluorescent imaging. In this work, the pentpeptide-rhodamine B derivative (YIGSR-RhB) and tripeptide-rhodamine B derivative (RGD-RhB) were synthesized respectively by using the solid phase synthesis methods. These derivatives were further characterized by 1HNMR, MS, UV and IR, etc. Their fluorescent and biocompatibility properties, such as the cell cytotoxicity, cell uptake and fluorescent imaging of tumor cells, and fluorescent imaging in BALB/c female mice with 4T1 tumors and C57 mice with B16F10 tumor in vivo, were also measured. Experiment results demonstrated that YIGSR-RhB and RGD-RhB possessed the low cell cytotoxicity, good tumor-targeting property and fluorescent properties similar to rhodamine B. Moreover, YIGSR-RhB and RGD-RhB can be taken up highly by the B16F10 melanoma cells and 4T1 breast cancer cells, and then achieve the good fluorescent imaging in these tumor cells in vitro and tumors of mice in vivo. Therefore, YIGSR-RhB and RGD-RhB can be used as the potential tumor-targeting probes for fluorescent imaging. They can directly attach the cell membrane and specifically target to the tumor cells.

A hydrophilic naphthalimide-based fluorescence chemosensor forCu2+ ion: Sensing properties, cell imaging and molecular logic behavior.

In this work, a hydrophilic naphthalimide-based fluorescence chemosensor (sensor 1) was synthesized for Cu2+ recognition, in which 2-(2-aminoethoxy)ethanol was introduced to improve the hydrophily and Schiff base acted as the multidentate ligand for Cu2+. The effect factors, sensing mechanism and regenerability of sensor 1 for Cu2+ sensing were systematically investigated. It was found that sensor 1 displayed a long emission wavelength of 532 nm upon excited in visible light region (436 nm), and the good water solubility made it utilized in aqueous media. It could selectively react with Cu2+ over other common metal ions to form a 2:1 complex within 1 min and result in significant fluorescence quench. The fluorescence change was linear to 0.5-10.0 µmol L-1 of Cu2+ with a low detection limit of 3.74 × 10-8 mol L-1. Sensor 1 has been successfully utilized for analyzing Cu2+ in water samples as well as imaging cellular Cu2+. Moreover, in view of fluorescence "on-off-on" switches of sensor 1 induced by Cu2+ and EDTA, an IMPLICATION logic gate was constructed based on fluorescence mode with Cu2+ and EDTA as inputs.

Converting waste lignin into nano-biochar as a renewable substitute of carbon black for reinforcing styrene-butadiene rubber.

Industrial waste lignin was commonly burnt or discharged into river in the past. However, in this study, lignin has been converted into high value-added nano-biochar as a renewable reinforcing filler of styrene-butadiene rubber (SBR) by a simple high-temperature carbonization treatment. Herein, the physicochemical change in lignin before and after carbonization was investigated. It was found that lignin-derived biochar (LB) consisted of vesicle-like primary nanoparticles which were closely packed to form "high-structure" irregular fragments with a high specific surface area (83.41 m2/g). When incorporating LB into SBR, the tensile properties of LB/SBR composites were significantly improved. At the filler loading of 40 phr, the tensile strength and elongation at break of the rubber composite were improved up to 7.1-folds and 2.4-folds of pristine SBR, respectively. Compared to commercial carbon black (CB) N330, the LB showed a similar reinforcing effect on SBR. However, the analysis on the morphology, stress-strain behavior and dynamic mechanical behavior suggested distinct reinforcing mechanisms for LB- and CB-filled rubber composites, due to the difference in the surface properties and structural characteristic of fillers. This work showed the application potential of LB as a renewable substitute of CB in rubber industry and brought environmental and economic benefits for the disposal of lignin.

A multi-functional drug delivery system based on polyphenols for efficient tumor inhibition and metastasis prevention.

Although chemotherapy is the most common method in clinical therapeutics with a straightforward mechanism, conventional anti-tumor drugs are still almost incapable of preventing the occurrence of tumor metastasis. In this study, we developed a multi-functional drug delivery system EINP@DOX consisting of a tea-derived polyphenol EGCG, iron ions and DOX. The system integrated the functions of tumor inhibition, diagnosis and metastasis prevention to achieve a systematic tumor treatment. The nanoscale size of EINP@DOX facilitated its accumulation in tumor tissues by means of the enhanced permeability and retention (EPR) effect, and it was then transferred to endosomes. The weakly acidic microenvironment in the endosomes of the tumor cells could destroy the coordination structure of EINP@DOX to realize the release of DOX for tumor therapy. Furthermore, the dissociative EGCG played the role of an adjuvant to restrain EMT and down-regulate the MMP levels, which could prevent the occurrence of tumor metastasis. Meanwhile, iron ions as superior magnetic resonance imaging (MRI) contrast agents provided visual evidence for the accurate location of EINP@DOX. In vitro and in vivo studies demonstrated that EINP@DOX showed a remarkable performance in tumor diagnosis and excellent therapeutic efficacy, inhibiting the metastasis of tumor cells effectively at the same time.

Al18 F labeled sulfonamide-conjugated positron emission tomography tracer in vivo tumor-targeted imaging.

An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high-resolution images in vivo. In this work, the aim was to evaluate the application of Al18 F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid containing sulfonamide group (18 F-Al-NOTA-SN) as a potential tumor-targeting signal-enhanced radioactive tracer in PET. SN as a tumor-targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18 F and AlCl3 to produce a compound 18 F-Al-NOTA-SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18 F-Al-NOTA-SN possessed low cell cytotoxicity and uptake to COS-7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA-MB-231, HepG2, and HeLa tumor cells in vitro. Moreover, 18 F-Al-NOTA-SN showed good tumor-targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18 F-Al-NOTA-SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor-targeting signal-enhanced radioactive tracer in PET.

Graphene as a nanofiller for enhancing the tribological properties and thermal conductivity of base grease.

During mechanical processes, violent friction and wear between the friction contact surfaces not only causes wear to mechanical components, reducing the instrument life, but also causes friction heat, reducing the working efficiency of machines during operation. The addition of graphene-reinforced grease to the mechanical friction surface can effectively reduce the friction coefficient and improve the thermal conductivity. In this work, the tribological properties and thermal conductivity of base grease with graphene were investigated systematically. The tribological results showed that the grease with 2 wt% graphene had the best tribological properties among all these greases. The wear scar diameter and average friction coefficient of graphene grease with 2 wt% graphene reached 0.43 mm and 0.10 (the values for base grease are 0.50 mm and 0.118), respectively. In addition, the average friction coefficient and wear scar diameter increased proportionally with the increasing load and frequency. The thermal conductivity of the grease with 4 wt% graphene reached 0.28 W (m K)-1, an increase of 55.5% in comparison with the base grease. It is proposed that the addition of graphene into the base grease effectively enhanced the tribological properties and thermal conductivity.

A self-delivery system based on an amphiphilic proapoptotic peptide for tumor targeting therapy.

In recent decades, drug self-delivery systems (DSDSs) have appeared with extraordinary superiority for cancer therapy while realizing intracellular delivery without supererogatory drug carriers. Here, we have designed and programmed a novel self-delivery system to realize tumor targeting therapy. The amphiphilic proapoptotic peptide KLAKLAKKLAKLAKGCK(Fmoc)2 (KLA) was used to form a self-assembled structure (KD) by encapsulating the hydrophobic anticarcinogen doxorubicin (DOX). Then, tumor recognizing hyaluronic acid (HA) was coated on the surface of KD to obtain a tumor targeting self-delivery system (KDH). The protective layer of HA could protect the therapeutic agents from being inactivated during blood circulation, and further specifically recognize tumor cells by the CD44 receptor after KDH had located the tumor regions. Additionally, hyaluronidase (HAase) overexpressed in the endosome of tumor cells could degrade the protective layer of HA and accelerate the liberation of KLA and DOX. The proapoptotic peptide KLA had the ability to locate mitochondria and induce mitochondrial dysfunction; meanwhile the anticarcinogen DOX diffused to the nuclei to inhibit the growth of tumor cells. Both in vitro and in vivo studies identified that our self-delivery system KDH possessed precise tumor targeting, and exhibited fantastic antitumor efficacy as well as negligible side effects.

Porphyrin-containing Gadolinium Complex as a Tumor-targeting Magnetic Resonance Imaging (MRI) Contrast Agent.

OBJECTIVE: Gadolinium diethylenetriaminepentaacetic di[5-(4'-amidophenyl)-10,15,20- tris(4'-sulfonatophenyl) porphyrin trisodium salt] (Gd-DTPA-2APTSPP) was synthesized by the reaction of diethylenetriaminepentaacetic dianhydride with 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin and subsequently chelation with gadolium chloride. METHODS: This gadolinium complex was characterized and its properties in vitro and in vivo were also evaluated. Compared with Gd-DTPA, Gd-DTPA-2APTSPP possessed high relaxivity r1, low cytotoxicity to HeLa cells and high enhanced signal intensities of the VX2 carcinoma in rabbits for a prolonged time. CONCLUSION: Moreover, Gd-DTPA-2APTSPP can distinguish the VX2 carcinoma from the reactive hyperplasia incited by inflammation and normal tissues in rabbits. Therefore, Gd-DTPA-2APTSPP can be taken up selectively by tumors and show the potential as a tumor-targeting MRI contrast agent.