Degradable Temperature-Sensitive Hydrogel Loaded with Heparin Effectively Prevents Post-Operative Tissue Adhesions.

Tissue adhesions could occur following surgeries, and severe tissue adhesions can lead to serious complications. Medical hydrogels could be applied at surgical sites as a physical barrier to prevent tissue adhesion. For practical reasons, spreadable, degradable, and self-healable gels are highly demanded. To meet these requirements, we applied carboxymethyl chitosan (CMCS) to poloxamer-based hydrogels to generate low Poloxamer338 (P338) content gels displaying low viscosity at refrigerator temperature and improved mechanical strength at body temperature. Heparin, an effective adhesion inhibitor, was also added to construct P338/CMCS-heparin composite hydrogel (PCHgel). PCHgel presents as a flowable liquid below 20 °C and could rapidly transform into gel when spread on the surface of damaged tissue due to temperature change. The introduction of CMCS enabled hydrogels to form a stable self-healable barrier at injured positions and slowly release heparin during the wound healing period before being degraded after ∼14 days. Ultimately, PCHgel significantly reduced tissue adhesion in model rats and displayed higher efficiency than P338/CMCS gel without heparin. Its adhesion suppression mechanism was verified, and it also displayed good biosafety. Therefore, PCHgel showed good clinical transformation potential with high efficacy, good safety, and ease of use.

Numerical solution of coupled nonlinear Klein-Gordon equations on unbounded domains.

The numerical solution of coupled nonlinear Klein-Gordon equations on unbounded domains is considered by applying the artificial boundary method. Based on the unified approach to overcome the coupled nonlinearity, local artificial boundary conditions are designed on the introduced artificial boundaries. The original problem is reduced to an initial boundary value problem on a bounded domain, which can be efficiently solved by the finite difference method. Some numerical examples are provided to verify the accuracy and effectiveness of the proposed method.

[Self-Aggregating Porphyrin-Based Photosensitizer Nano Micelles for Photodynamic Therapy].

Objective: To prepare supramolecular photosensitizer that can be retained at the site of tumors and that has high light conversion efficiency so as to improve the efficacy of tumor photodynamic therapy (PDT). Methods: A covalent organic framework material based on amino tetraphenyl porphyrin (Tapp), henceforth referred to as Tapp-COF, was synthesized. The spectral characteristics, energy gap characteristics and singlet oxygen generation ability of the material were characterized. Then, Tapp-COF was processed by thin film hydration method to derive T-C@PP, a nano micelle unstable in physiological environment. The same method was used to process Tapp in order to make T@PP micelles, which were used as the controls. The particle size, potential, surface morphology and stability were examined. B16F10 mouse melanoma cells were injected subcutaneously into C57 mice and T-C@PP or T@PP were injected intratumorally, followed by light exposure or no light exposure. We assessed the in vitro photodynamic killing efficiency of the nano micelles and the status of tumor cells co-cultured with the photosensitizer micelles and validated the tumor retention ability and killing efficiency of the micelles . Results: Compared with Tapp, Tapp-COF displayed higher photodynamic conversion efficiency, and could produce more ROS. The T-C@PP micelles were unstable in physiological environment, and adsorptive aggregation would occur after co-culturing with tumor cells for a period of time. T-C@PP showed low cytotoxicity when there was no light exposure, but could kill tumor cells at relatively low concentration under 660 nm laser irradiation. T-C@PP could be retained in tumor tissue, and had better in vivo killing efficiency that that of T@PP. Conclusion: In this study, highly efficient TPP-COF based T-C@PP micelles were prepared. Under physiological conditions, these micelles could achieve tumor retention through self-aggregation. Possessing sound safety, the nano micelles showed promise for potential application in tumor PDT.

SUPG-Stabilized Virtual Element Method for Optimal Control Problem Governed by a Convection Dominated Diffusion Equation.

In this paper, the streamline upwind/Petrov Galerkin (SUPG) stabilized virtual element method (VEM) for optimal control problem governed by a convection dominated diffusion equation is investigated. The virtual element discrete scheme is constructed based on the first-optimize-then-discretize strategy and SUPG stabilized virtual element approximation of the state equation and adjoint state equation. An a priori error estimate is derived for both the state, adjoint state, and the control. Numerical experiments are carried out to illustrate the theoretical findings.

Collagenase-loaded pH-sensitive nanocarriers efficiently remodeled tumor stroma matrixes and improved the enrichment of nanomedicines.

The dense extracellular matrix (ECM) in tumor tissue severely hinders the penetration and enrichment of antitumor nanomedicines, which could significantly affect their efficiency. In this study, we used pH-sensitive nanocarriers loaded with collagenase (Col) to remold the tumor microenvironment (TME). Furthermore, we combined the collagenase delivery system with a nanomedicine to improve its penetration and enrichment in the tumor, thereby improving efficacy. We synthesized acetalated dextran (Ace-DEX) with an ideal pH-sensitivity as the carrier material of collagenase. Under mild preparation conditions, collagenase was loaded into Ace-DEX nanoparticles (NPs) with a high loading capacity (>4%) and remained highly active (>90%). Col-carrying NPs (Col-NPs) significantly reduced the tumor collagen content by 15.1%. Pretreatment with Col-NPs increased the accumulation of doxorubicin (DOX)-loaded liposome (DOX-Lipo) in the tumor by 2.8-fold. There were no safety concerns as the Col-NP showed no significant toxicity and reduced Col-induced damage to healthy tissues. Additionally, the number of circulating tumor cells remained unchanged after Col-NP treatment, suggesting no increased risk of tumor metastasis. Because the Col-NP acts essentially independent of the subsequent treatment, it has considerable potential for enhancing many existing delivery systems and drugs for cancer treatment. It may also be used for treating other collagen-related diseases.

Advances in photosensitizer-related design for photodynamic therapy.

Photodynamic therapy (PDT) is highly effective in treating tumors located near body surface, offering strong tumor suppression and low damage to normal tissue nearby. PDT is also effective for treating a number of other conditions. PDT not only provide a precise and selective method for the treatment of various diseases by itself, it can also be used in combination with other traditional therapies. Because PDT uses light as the unique targeting mechanism, it has simpler and more direct targeting capability than traditional therapies. The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances. Different photosensitizers have their distinct characteristics, leading to different advantages and disadvantages. These could be enhanced or compensated by using proper PDT system. Therefore, the selected type of photosensitizer would heavily influence the overall design of a PDT system. In this article, we evaluated major types of inorganic and organic PDT photosensitizers, and discussed future research directions in the field.