PGMA-Based Cationic Nanoparticles with Polyhydric Iodine Units for Advanced Gene Vectors

It is crucial for successful gene delivery to develop safe, effective, and multifunctional polycations. Iodine-based small molecules are widely used as contrast agents for CT imaging. Herein, a series of star-like poly­(glycidyl methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking polyhydric iodine units are prepared for multifunctional gene delivery systems. The proposed II-PGEA/II star vector is composed of one iohexol intermediate (II) core and five ethanolamine (EA) and II-difunctionalized PGMA arms. The amphipathic II-PGEA/II vectors readily self-assemble into well-defined cationic nanoparticles, where massive hydroxyl groups can establish a hydration shell to stabilize the nanoparticles. The II introduction improves cell viabilities of polycations. Moreover, by controlling the suitable amount of introduced II units, the resultant II-PGEA/II nanoparticles can produce fairly good transfection performances in different cell lines. Particularly, the II-PGEA/II nanoparticles induce much better in vitro CT imaging abilities in tumor cells than iohexol (one commonly used commercial CT contrast agent). The present design of amphipathic PGMA-based nanoparticles with CT contrast agents would provide useful information for the development of new multifunctional gene delivery systems

Controllable Heparin-Based Comb Copolymers and Their Self-assembled Nanoparticles for Gene Delivery

Polysaccharide-based copolymers have attracted much attention due to their effective performances. Heparin, as a kind of polysaccharide with high negative charge densities, has attracted much attention in biomedical fields. In this work, we report a flexible way to adjust the solubility of heparin from water to oil via the introduction of tetrabutylammonium groups for further functionalization. A range of heparin-based comb copolymers with poly­(poly­(ethylene glycol) methyl ether methacrylate) (PPEGMEMA), poly­(dimethylaminoethyl methacrylate) (PDMAEMA), or PPEGMEMA-<i>b</i>-PDMAEMA side chains were readily synthesized in a MeOH/dimethylsulfoxide mixture via atom-transfer radical polymerization. The heparin-based polymer nanoparticles involving cationic PDMAEMA were produced due to the electrostatic interaction between the negatively charged heparin backbone and PDMAEMA grafts. Then the pDNA condensation ability, cytotoxicity, and gene transfection efficiency of the nanoparticles were characterized in comparison with the reported gene vectors. The nanoparticles were proved to be effective gene vectors with low cytotoxicity and high transfection efficiency. This study demonstrates that by adjusting the solubility of heparin, polymer graft functionalization of heparin can be readily realized for wider applications

Versatile Types of MRI-Visible Cationic Nanoparticles Involving Pullulan Polysaccharides for Multifunctional Gene Carriers

Owing to the low cytotoxicity and excellent biocompatibility, polysaccharides are good candidates for the development of promising biomaterials. In this paper, a series of magnetic resonance imaging (MRI)-visible cationic polymeric nanoparticles involving liver cell-targeting polysaccharides were flexibly designed for multifunctional gene delivery systems. The pullulan-based vector (PuPGEA) consisting of one liver cell-targeting pullulan backbone and ethanolamine-functionalized poly­(glycidyl methacrylate) (denoted by BUCT-PGEA) side chains with abundant hydroxyl units and secondary amine was first prepared by atom transfer radical polymerization. The resultant cationic nanoparticles (PuPGEA-GdL or PuPGEA-GdW) with MRI functions were produced accordingly by assembling PuPGEA with aminophenylboronic acid-modified Gd-DTPA (GdL) or GdW₁₀O₃₆^9– (GdW) via the corresponding etherification or electrostatic interaction. The properties of the PuPGEA-GdL and PuPGEA-GdW nanoparticles including pDNA condensation ability, cytotoxicity, gene transfection, cellular uptake, and in vitro and in vivo MRI were characterized in details. Such kinds of cationic nanoparticles exhibited good performances in gene transfection in liver cells. PuPGEA-GdW demonstrated much better MRI abilities. The present design of PuPGEA-based cationic nanoparticles with the liver cell-targeting polysaccharides and MRI contrast agents would shed light on the exploration of tumor-targetable multifunctional gene delivery systems

A Facile Strategy to Prepare Hyperbranched Hydroxyl-Rich Polycations for Effective Gene Therapy

For effective gene therapy, nonviral gene carriers with low toxicity and high transfection efficiency are of much importance. In this work, we developed a facile strategy to prepare hyperbranched hydroxyl-rich polycations (denoted by TE) by the one-pot method involving ring-opening reactions between two commonly used reagents, ethylenediamine (ED) with two amino groups and 1,3,5-triglycidyl isocyanurate (TGIC) with three epoxy groups. The hyperbranched TEs with different molecular weights were investigated on their DNA condensation ability, protein absorption property, biocompatibility, transfection efficiency, and in vivo cancer therapy and toxicity. TE exhibited low cytotoxicity and protein absorption property due to the plentiful hydroxyl groups. The optimal transfection efficiency of TE was significantly higher than that of the gold standard polycationic gene carrier branched polyethylenimine (PEI, 25 kDa). Furthermore, TE was applied for in vivo tumor inhibition by the delivery of antioncogene p53, which showed good antitumor efficiency with low adverse effects. The present work provides a new concept for the facile preparation of hyperbranched hydroxyl-rich polycationic carriers with good transfection performances

Polymer-Encapsulated Lanthanide-Containing Clusters as Platforms for Fabricating Magnetic Soft Materials

Although many high-nuclearity lanthanide-containing clusters with aesthetical topological nanoarchitectures and unique magnetic properties have been synthesized, there was a big time lag to develop functional soft materials and devices on the basis of these clusters, because of their stability and processability. Herein, we report a universal strategy to fabricate lanthanide cluster based magnetic soft materials under ambient conditions. The prototypical cluster [Gd₅₂Ni₅₆(IDA)₄₈(OH)₁₅₄(H₂O)₃₈]¹⁸⁺ was encapsulated as an inorganic core by polymeric shells of sulfonate end functionalized poly­(ethylene glycol) monoalkyl ethers through electrostatic interaction. The thickness of the shell was readily controlled by precisely tuning length of the polymer chain, leading to controllably reduced antiferromagnetic interactions between the clusters. The encapsulated hybrids can self-assemble to form vesicles in solution and can be used as an excellent agent for in vivo magnetic resonance imaging

Antimicrobial and Antifouling Polymeric Agents for Surface Functionalization of Medical Implants

Combating implant-associated infections is an urgent demand due to the increasing numbers in surgical operations such as joint replacements and dental implantations. Surface functionalization of implantable medical devices with polymeric antimicrobial and antifouling agents is an efficient strategy to prevent bacterial fouling and associated infections. In this work, antimicrobial and antifouling branched polymeric agents (GPEG and GEG) were synthesized via ring-opening reaction involving gentamicin and ethylene glycol species. Due to their rich primary amine groups, they can be readily coated on the polydopamine-modified implant (such as titanium) surfaces. The resultant surface coatings of Ti-GPEG and Ti-GEG produce excellent <i>in vitro</i> antibacterial efficacy toward both Staphylococcus aureus and Escherichia coli, while Ti-GPEG exhibit better antifouling ability. Moreover, the infection model with S. aureus shows that implanted Ti-GPEG possessed excellent antibacterial and antifouling ability <i>in vivo</i>. This study would provide a promising strategy for the surface functionalization of implantable medical devices to prevent implant-associated infections

Poly(aspartic acid)-based Degradable Assemblies for Highly Efficient Gene Delivery

Due to its good properties such as low cytotoxicity, degradability, and biocompatibility, poly­(aspartic acid) (PAsp) is a good candidate for the development of new drug delivery systems. In this work, a series of new PAsp-based degradable supramolecular assemblies were prepared for effective gene therapy via the host–guest interactions between the cyclodextrin (CD)-cored PAsp-based polycations and the pendant benzene group-containing PAsp backbones. Such supramolecular assemblies exhibited good degradability, enhanced pDNA condensation ability, and low cytotoxicity. More importantly, the gene transfection efficiencies of supramolecular assemblies were much higher than those of CD-cored PAsp-based counterparts at various N/P ratios. In addition, the effective antitumor ability of assemblies was demonstrated with a suicide gene therapy system. The present study would provide a new means to produce degradable supramolecular drug delivery systems

DataSheet_1_A population-based predictive model identifying optimal candidates for primary and metastasis resection in patients with colorectal cancer with liver metastatic.zip

BackgroundThe survival benefit of primary and metastatic resection for patients with colorectal cancer with liver metastasis (CRLM) has been observed, but methods for discriminating which individuals would benefit from surgery have been poorly defined. Herein, a predictive model was developed to stratify patients into sub-population based on their response to surgery.MethodsWe assessed the survival benefits for adults diagnosed with colorectal liver metastasis by comparing patients with curative surgery vs. those without surgery. CRLM patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were identified for model construction. Other data including CRLM patients from our center were obtained for external validation. Calibration plots, the area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram compared with the tumor–node–metastasis (TNM) classification. The Kaplan–Meier analysis was performed to examine whether this model would distinguish patients who could benefit from surgery.ResultsA total of 1,220 eligible patients were identified, and 881 (72.2%) underwent colorectal and liver resection. Cancer-specific survival (CSS) for the surgery group was significantly better than that for the no-surgery group (41 vs. 14 months, p ConclusionsAn accurate and easy-to-use CRLM nomogram has been developed and can be applied to identify optimal candidates for the resection of primary and metastatic lesions among CRLM patients.</p