In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles.

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.

Self-forming double-crosslinked hydrogels by the marriage of catechols and enzyme mimetic polymers.

Self-forming double-crosslinked (DC) hydrogels were designed by incorporating enzyme-mimicking metal coordination polymer crosslinks and catechol chemistry. A macromolecular tris-histidine copper complex acted both as part of the hydrogel network and as a catalyst of catechol oxidation to induce a second hydrogel network by covalent crosslinking of catechol functionalized polymers thus giving catalytic control over hydrogel crosslinking.

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer.

OBJECTIVE: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. METHODS: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. RESULTS: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. CONCLUSIONS: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Remotely Triggered Liquefaction of Hydrogel Materials.

Adaptable behavior such as triggered disintegration affords a broad scope and utility for (bio)materials in diverse applications in materials science and engineering. The impact of such materials continues to grow due to the increased importance of environmental considerations as well as the increased use of implants in medical practices. However, examples of such materials are still few. In this work, we engineer triggered liquefaction of hydrogel biomaterials in response to internal, localized heating, mediated by near-infrared light as external stimulus. This adaptable behavior is engineered into the readily available physical hydrogels based on poly(vinyl alcohol), using gold nanoparticles or an organic photothermal dye as heat generators. Upon laser light irradiation, engineered biomaterials underwent liquefaction within seconds. Pulsed laser light irradiation afforded controlled, on-demand release of the incorporated cargo, successful for small molecules as well as proteins (enzymes) in their biofunctional form.

Studies of poly(ethylene glycol) modification of HM-3 polypeptides.

An RGD modified endostatin-derived synthetic peptide, named HM-3, is a polypeptide angiogenesis inhibitor previously synthesized in our laboratory. Its robust inhibitory effects on endothelial cell migration and tumor growth have been demonstrated by in vivo and in vitro activity assays. The RGD integrin recognition sequence enables the selective binding of HM-3 and its specific targeting to tumor cells that express high levels of integrin. However, the drug has relatively short half-life in vivo, thus requiring administration twice a day to achieve its optimal in vivo antitumor efficacy. In the current study designed to prolong HM-3 half-life, we used methoxy-poly(ethylene glycol)-aldehyde (mPEG-ALD) to specifically modify its N terminus and optimized the reaction condition via monitoring the modification by reverse-phase high-performance liquid chromatograph (RP-HPLC) under varying stoichiometric ratios (n(mPEG10k-ALD):n(HM-3)), reaction times, and pH values. The maximal modification rate was achieved in a reaction when substrates mPEG10k-ALD and HM-3 were mixed at the molar ratio of 2:1 in a pH 6 phosphate buffer after 4 h incubation at room temperature. The reaction product of this optimal reaction was purified to 96% purity by RP-HPLC. Compared with HM-3, the newly modified PEG(10k)-HM-3 was shown to be more active in the inhibition of angiogenesis in the chorioallantoic membrane of chick embryos (CAM), its rate of in vitro degradation in serum was markedly reduced, and its in vivo half-life was prolonged by 5.86-fold relative to unmodified HM-3 after intravenous injection into male SD rats.

Magnetite loaded Polypeptide-PLGA multifunctional microbubbles for dual-mode US/MR imaging.

Magnetite loaded Polypeptide-PLGA multifunctional microbubbles (Fe3O4 /Polypeptide-PLGA MMBs) that show superparamagnetic properties were prepared by a modified double emulsion method and employed as imaging agent for dual-mode Ultrasound/Magnetic resonance (US/MR) imaging of prostatic cancer. The successful synthesis of MMBs was determined by Fourier Transform Infrared Spectrometer (FTIR), X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), Atomic Absorption Spectroscopy (AAS) and vibrating sample magnetometer (VSM). The as-prepared MMBs had a diameter of 700 nm and were quite safe as confirmed by MTT assays. Prussian Blue Staining showed that targeted Fe3O4 /Polypeptide-PLGA MMBs enhanced the cellular uptake efficiency. In cell attachment study, adherence of MMBs was significantly higher to LNCaP cells compared with negative control PC3 cells. The in vitro results demonstrated that these MMBs could enhance both US and MR imaging of prostatic cancer.