Target Embolization Combined with Multimodal Thermal Ablation for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

Noninterventional embolization does not require the use of a catheter, and the treatment of solid tumors in combination with thermal ablation can avoid some of the risks of the surgical procedure. Therefore, we developed an efficient tumor microenvironment-gelled nanocomposites with poly [(l-glutamic acid-ran-l-tyrosine)-b-l-serine-b-l-cysteine] (PGTSCs) coated-nanoparticles (Fe3O4&Au@PGTSCs), from which the prepared PGTSCs were given possession of pH response to an acidic tumor microenvironment. Fe3O4&Au@PGTSC in noninterventional embolization treatment not only achieved the smart targeted medicine delivery but also meshed with noninvasive multimodal thermal ablation therapy and multimodal imaging of solid tumors via intravenous injection. It was worth noting that the results of animal experiments in vivo demonstrated that Fe3O4&Au@PGTSCs have specific tumor accumulation and embolization and thermal ablation effects; at 10 days postinjection, only scars were found at the tumor site. After 20 days, the tumors of model mice completely disappeared. This device is easier to treat solid tumors based on the slightly acidic tumor environment.

A Simple and Efficient Embolization-Combined Therapy for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

Interventional embolization and minimally invasive thermal ablation are common clinical methods for treatment of unresectable solid tumors, but they both have many insurmountable disadvantages. Inspired by pH-responsive drug delivery systems, we report the tumor microenvironment-gelled nanocomposites with poly[(l-glutamic acid-ran-l-tyrosine)-b-l-threonine-b-l-cysteine]s (PGTTCs) coating nanoparticles (NPs, Au or Fe3O4) for noninterventional targeted embolization combined with noninvasive thermal ablation therapy of solid tumors by intravenous injection without catheter use. The results of the animal trial in vivo with tumor-bearing mice and rabbits showed superior targeted embolization and therapy and fluorescence/single-photon emission computed tomography/magnetic resonance multimodal imaging effects. Tumors treated with NPs@PGTTCs were shrunken and necrotized within 30 days, the long-term survival rate was more than 80%, and the same effects can be achieved within 15 days when combined with thermal ablation. The method is so simple and efficient for many hard-to-treat tumors within an acidic microenvironment, which is not only a great improvement and innovation in tumor theranostics but also an important development in nanomedicine.

Smart-Polypeptide-Coated Mesoporous Fe3O4 Nanoparticles: Non-Interventional Target-Embolization/Thermal Ablation and Multimodal Imaging Combination Theranostics for Solid Tumors.

Tumor theranostics hold great potential for personalized medicine in the future, and transcatheter arterial embolization (TAE) is an important clinical treatment for unresectable or hypervascular tumors. In order to break the limitation, simplify the procedure of TAE, and achieve ideal combinatorial theranostic capability, here, a kind of triblock-polypeptide-coated perfluoropentane-loaded mesoporous Fe3O4 nanocomposites (PFP-m-Fe3O4@PGTTCs) were prepared for non-interventional target-embolization, magnetic hyperthermia, and multimodal imaging combination theranostics of solid tumors. The results of systematic animal experiments by H22-tumor-bearing mice and VX2-tumor-bearing rabbits in vivo indicated that PFP-m-Fe3O4@PGTTC-6.3 has specific tumor accumulation and embolization effects. The tumors' growth has been inhibited and the tumors disappeared 4 weeks and ≤15 days post-injection with embolization and magnetic hyperthermia combination therapy, respectively. The results also showed an excellent effect of magnetic resonance/ultrasound/SPECT multimodal imaging. This pH-responsive non-interventional embolization combinatorial theranostics system provides a novel embolization and multifunctional theranostic candidate for solid tumors.

Heparin-like anticoagulant polypeptides with tunable activity: Synthesis, characterization, anticoagulative properties and clot solubilities in vitro.

Due to the uncontrollable anticoagulant activity and limited source, Heparin, which is commonly used in clinical anticoagulation therapies, faces the risk of spontaneous bleeding and thrombocytopenia. Herein, a series of anionic poly(amino acid) s poly (l-Serine-ran-L-Glutamic acid-ran-L-Cysteine-SO3) (PSEC-SO3) were prepared by the controlled Ring Opening Polymerization (ROP) of N-Carboxyanhydrides (NCAs). The anticoagulant activities of PSEC-SO3 can be regulated by simply adjusting the feeding ratio of monomers. In vitro tests show that these polypeptides can effectively prolong the Activated Partical Thromboplastin Time (APTT) and inhibit Factor IIa and Factor Xa, but has no significant effect on Prothrombin Time (PT) and Thrombin Time (TT), which indicates that PSEC-SO3 mainly act on the intrinsic pathway. In summary, the activity-tunable heparin-like polypeptides are expected to have good application prospects in the anticoagulant field.

Tumor Noninvasive and Target Embolization Therapy Platform by Intravenous Injection Based on Acidic Microenvironment-Responsive Hyperbranched Poly(amino acid)s.

Transcatheter arterial embolization (TAE) has been widely applied in treatments of unresectable or hypervascular tumors, but the procedure of TAE is complicated possibly brings inherent risks. Here, inspired by pH-responsive drug delivery systems, a new method of noninvasive and target embolization therapy by intravenous injection was developed. This method is based on a type of acidic microenvironment-responsive hyperbranched poly(amino acid) (HPTTG) to avoid using catheterization and real-time image guidance angiography, simplifying the procedure, elevating compliance and general applicability of embolization therapy. The pH value of the sol-to-gel phase transition with decreasing pH of HPTTG was controlled by adjusting the ratio of acidic amino acids in copolymers. The results of the tumor-bearing animal experiment indicate that the HPTTG have an excellent target and embolic ability; they accumulate the most at the tumor site in 8 h postinjection. Blood vessels of the tumors were occluded, and the tumors were inhibited and necrotized in about 20 days. Therefore, it is expected that HPTTG not only can be used as novel embolic materials for efficient noninvasive embolization therapy of many solid tumors but also can be used as a multifunctional platform for combined theranostics, for example, combination with controlled release, thermal ablation, multimodal imaging, synergistic therapy, etc.

Biomimetic chitosan-graft-polypeptides for improved adhesion in tissue and metal.

Inspired by the mussel foot protein and chitosan-based macromolecular adhesives, a series of chitosan-graft-polypeptides were synthesized by ring-opening polymerization of three N-carboxyanhydrides (NCAs) - 3,4-dihydroxyphenylalanine-N-carboxyanhydride (DOPA-NCA), cysteine-NCA (Cys-NCA) and arginine-NCA (Arg-NCA) - using partial-NH2-protected chitosan as an initiator. These copolymers demonstrated good biodegradability and low cytotoxicity. The results of lap-shear adhesion test showed that the maximum lap-shear adhesion strength on the porcine skin and aluminum sheet were 195.97 ± 21.1 kPa and 3080 ± 320 kPa, respectively, and the maximum tensile adhesion strength on bone was 642.70 ± 61.1 kPa. The rat experiment in vivo showed that these copolymers exhibited good hemostatic performance and can promote the healing of skin wound and bone fracture. It is expected that thesecopolymeric adhesives will have broad applications in hemostasis and soft tissue adhesions.

All-in-one hyperbranched polypeptides for surgical adhesives and interventional embolization of tumors.

A series of hyperbranched, thermo-responsive and mussel-inspired polypeptides were synthesized and used for surgical adhesion, hemostasis and interventional embolization. These polypeptides showed excellent tissue-adhesive properties according to adhesive strength tests on porcine skin and bone in vitro, where the maximum lap-shear adhesion strength on porcine skin was 114.5 kPa and the maximum tensile adhesion strength on bone was 786 kPa. In vivo animal experiments indicated that these polypeptides exhibit superior hemostatic properties and healing effects in skin incisions and osteotomy gap; the skin incision healing and osteotomy gap remodeling were completed in all rats after 14 and 60 days, respectively. In vivo evaluation of the embolization ability of these polypeptides was performed on rabbit kidney models, resulting in successful occlusion of renal arteries, which led to gross ischemic changes in the embolized kidneys up to 16 days. A trial embolization procedure on H22 tumor-bearing rat models also confirmed the gelability of these polypeptides in tumor arteries, which might cause damage to embolized tumors. Therefore, these polypeptides are expected to be good candidates as surgical tissue adhesives, antibleeding materials, and effective embolic materials.

Mussel-Inspired Thermoresponsive Polypeptide-Pluronic Copolymers for Versatile Surgical Adhesives and Hemostasis.

Inspired by marine mussel adhesive proteins, polymers with catechol side groups have been extensively explored in industrial and academic research. Here, Pluronic L-31 alcoholate ions were used as the initiator to prepare a series of polypeptide-Pluronic-polypeptide triblock copolymers via ring-opening polymerization of l-DOPA-N-carboxyanhydride (DOPA-NCA), l-arginine-NCA (Arg-NCA), l-cysteine-NCA (Cys-NCA), and ε-N-acryloyl lysine-NCA (Ac-Lys-NCA). These copolymers demonstrated good biodegradability, biocompatibility, and thermoresponsive properties. Adhesion tests using porcine skin and bone as adherends demonstrated lap-shear adhesion strengths up to 106 kPa and tensile adhesion strengths up to 675 kPa. The antibleeding activity and tissue adhesive ability were evaluated using a rat model. These polypeptide-Pluronic copolymer glues showed superior hemostatic properties and superior effects in wound healing and osteotomy gaps. Complete healing of skin incisions and remodeling of osteotomy gaps were observed in all rats after 14 and 60 days, respectively. These copolymers have potential uses as tissue adhesives, antibleeding, and tissue engineering materials.

2-[(3R,6R)-6-Methyl-2,5-dioxomorph-olin-3-yl]-N-(propan-2-yl)acetamide.

The molecular conformation of the title compound, C(10)H(16)N(2)O(4), is determined by an intra-molecular N-H⋯O hydrogen bond involving the morpholine NH group and the amide O atom. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into chains along the a-axis direction.