PEG Mn Research Articles

Dual-modality and Noninvasive Diagnostic of MNP-PEG-Mn Nanoprobe for Renal Fibrosis Based on Photoacoustic and Magnetic Resonance Imaging.

To date, imaging-guided multimodality therapy is important to improve the accuracy of the diagnosis of renal fibrosis, and nanoplatforms for imaging-guided multimodality diagnosis are gaining more and more attention. There are many limitations and deficiencies in clinical use for early-stage diagnosis of renal fibrosis, and multimodal imaging can contribute more thoroughly and provide in-detail information for effective clinical diagnosis. Melanin is an endogenous biomaterial, and we developed an ultrasmall particle size melanin nanoprobe (MNP-PEG-Mn) based on photoacoustic (PA) and magnetic resonance (MR) dual-modal imaging. MNP-PEG-Mn nanoprobe, with the average diameter about 2.7 nm, can be passively targeted for accumulation in the kidney, and it has excellent free radical scavenging and antioxidant abilities without further exacerbating renal fibrosis. Using the normal group signal as a control, the dual-modal imaging results showed that the MR imaging (MAI) and PA imaging (PAI) signals reached the strongest at 6 h when MNP-PEG-Mn entered the 7 day renal fibrosis group via the left vein of the tail end of the mice; however, the strength of the dual-modal imaging signal and the gradient of signal change were significantly weaker in the 28 day renal fibrosis group than in the 7 day renal fibrosis group and normal group. The phenomenon preliminarily indicates that as a PAI/MRI dual-modality contrast medium candidate, MNP-PEG-Mn has outstanding ability in clinical application potential.

Biodistribution Analysis of NIR-Labeled Nanogels Using in Vivo FMT Imaging in Triple Negative Human Mammary Carcinoma Models.

The purpose of this study is to evaluate the biodistribution properties of random-copolymer-based core-cross-linked nanogels of various sizes and surface poly(ethylene glycol) composition. Systematic variations of near-IR labeled nanogels, comprising varying particle sizes (28-135 nm), PEG corona quantity (0-50 mol %), and PEG length (PEG Mn 1000, 2000, and 5000), were prepared and injected in mice that had been subcutaneously implanted with MDA-MB-231-luc-D3H2LN human mammary carcinoma. In vivo biodistribution was obtained using fluorescence molecular tomography imaging at 0, 6, 24, 48, and 72 h postinjection. Retention of total body probe and percentages of total injected dose in the tumor, liver, spleen, lungs, heart, intestines, and kidneys were obtained. Smaller nanogels (∼30-40 nm) with a high PEG conjugation (∼43-46 mol %) of Mn 2000 on their coronas achieved the highest tumor specificity with peak maximum 27% ID/g, a statistically significant propensity toward accumulation with 16.5% ID/g increase from 0 to 72 h of imaging, which constitutes a 1.5-fold increase. Nanogels with greater tumor localization also had greater retention of total body probe over 72 h. Nanogels without extensive PEGylation were rapidly excreted, even at similar sizes to PEGylated nanogels exhibiting whole body retention. Of all tissues, the liver had the highest % ID, however, like other tissues, it displayed a monotonic decrease over time, suggesting nanogel clearance by hepatic metabolism. Ex vivo quantification of individual tissues from gross necropsy at 72 h postinjection generally correlated with the FMT analysis, providing confidence in tissue signal segmentation in vivo. The parameters determined to most significantly direct a nanogel to the desired tumor target can lead to improve effectiveness for nanogels as therapeutic delivery vehicles.

Tuning and Predicting Mesh Size and Protein Release from Step Growth Hydrogels.

Hydrogel-based depots are of growing interest for release of biopharmaceuticals; however, a priori selection of hydrogel compositions that will retain proteins of interest and provide desired release profiles remains elusive. Toward addressing this, in this work, we have established a new tool for the facile assessment of protein release from hydrogels and applied it to evaluate the effectiveness of mesh size estimations on predicting protein retention or release. Poly(ethylene glycol) (PEG)-based hydrogel depots were formed by photoinitiated step growth polymerization of four-arm PEG functionalized with norbornene (PEG-norbornene, 4% w/w to 20% w/w, Mn ∼ 5 to 20 kDa) and different dithiol cross-linkers (PEG Mn ∼ 1.5 kDa or enzymatically degradable peptide), creating well-defined, robust materials with a range of mesh sizes estimated with Flory-Rehner or rubber elasticity theory (∼5 to 15 nm). A cocktail of different model proteins was released from compositions of interest, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to facilely and quantitatively analyze temporal release profiles. Mesh size was predictive of retention of relatively large proteins and release of relatively small proteins. Proteins with diameters comparable to the mesh size, which is often the case for growth factors, were released by hindered diffusion and required experimental assessment of retention and release. With this knowledge, hydrogels were designed for the controlled release of a therapeutically relevant growth factor, PDGF-BB.

Controlled WISP-1 shRNA Delivery Using Thermosensitive Biodegradable Hydrogel in the Treatment of Osteoarthritis

This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis (OA). OA is a chronic debilitating disease. Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 °C, we synthetized the hydrogels via ring-opening copolymerization of lactide (LA) and glycolide (GA) using Polyethylene glycol (PEG Mn = 1000) and stannous octoate (Sn(Oct)2, 95%) as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP-1shRNA and PEI-Lys in distilled water at 4.0 °C. Then, the WISP-1shRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 °C. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP1 in synoviocytes. Therefore, the hydrogel containing WISP-1shRNA is demonstrated an efficient way for the treatment of OA.

Dendronized multifunctional amphiphilic polymers as efficient nanocarriers for biomedical applications.

To gain insight into the factors that affect stability and transport efficiency under dilution conditions, dendronized and hyperbranched multifunctional amphiphilic polymers are synthesized by following the "grafting to" approach using varied amounts of propargylated alkyl chain with perfect and hyperbranched polyglycerol dendrons on the base copolymer of PEG (Mn: 1000 g mol(-1)) diethylester and 2-azidopropane-1,3-diol following the "bio-catalytic method" and "click approach". The dendronized and hyperbranched polymeric systems form supramolecular aggregates and exhibit an efficient transport potential for the model dye "Nile red" in the low μm range in the core-shell-type architecture provided with distinct amphiphilicity as required for encapsulation. Cytotoxicity studies show the polymeric systems to be non-toxic over a wide concentration range. The cellular internalization of Nile-red-encapsulated supramolecular micellar structures is also studied using cellular fluorescence micro-scopy and fluorescence-activated cell sorting (FACS) measurements. A comparison of the data for the dendronized polymers (PEG Mn: 600/1000 g mol(-1)) with the respective low-molecular-weight amphiphile reveal that these polymeric systems are excellent nanotransporters.

Self-assembly of poly(ethylene glycol)-block-polypyridine copolymer into micelles and at silica surface: effect of molecular architecture on silica dispersion

We have newly synthesized amphiphilic block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic pyridine segments (PEG-b-Py). Chain transfer agent-terminated PEG was subsequently chain-extended with 3-(4-pyridyl)-propyl acrylate to obtain PEG-b-Py by reversible additional-fragmentation chain transfer polymerization. Particularly, the effect of varying molecular weight (Mn) of PEG (Mn = 2,000 and 5,000) and Py in the block copolymers was investigated in terms of critical micelle concentration, pyrene solubilization, micelle size distribution, and association number per micelle. Based on the amphiphilic balance, PEG-b-Pys formed core-shell type polymer micelle. The association number of PEG2k-b-Py was higher than that of PEG5k-b-Py, suggesting the degree of phase separation strongly depended on PEG Mn. Furthermore, the adsorption of PEG-b-Py copolymer onto silica nanoparticles as dispersant was studied to estimate the effect of PEG Mn in the copolymers and their solubility in the medium on the adsorption. Adsorbed density of PEG2k-b-Py copolymer onto silica nanoparticle was higher than that of PEG5k-b-Py, which was significantly correlated with the degree of phase separation. Furthermore, the adsorbed amount of copolymer increased with the increase in ionic strength due to the reduced solubility of PEG in the buffer solution. The resultant dispersion stability was highly correlated with the graft density of copolymer onto silica surface. However, the stability of PEG2k-b-Py coated particles was lower than that with PEG5k-b-Py, this is attributed to the relatively thin layer of PEG at the silica surface, which cannot provide the system with sufficient steric stabilization as the salt concentration increases. These fundamental investigations for the surface modification of the nanoparticle provide the insight into the highly stable colloidal dispersion, particularly in the physiological condition with high ionic strength.

Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

The morphology, miscibility, and specific interactions of paclitaxel (PTx) with a family of polyhedral oligosilsesquioxane (POSS)-based biodegradable thermoplastic polyurethanes (POSS TPUs) were investigated systematically using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). These POSS TPUs incorporate an alternating multiblock structure formed by POSS hard segments and the soft segments composed of polylactide/caprolactone copolymer (P(DLLA-co-CL)). They feature variable poly(ethylene glycol) (PEG) content from 0 to 14 wt % through adjusting the poly(ethylene glycol) (PEG) molecular weight in P(DLLA-co-CL) soft segments of fixed molar mass of Mn = 12 kg/mol and further to 52 wt % utilizing pure PEG Mn = 1 kg/mol in the soft segments. Using WAXD, it was found that PTx is amorphous in all proportions in the PTx/POSS TPU blends prepared using a solution-casting method. Interestingly, the PTx not only exhibits excellent misc...