Injectable Hydrogel Based on Modified Gelatin and Sodium Alginate for Soft-Tissue Adhesive.

To assist or replace the traditional suture techniques for wound closure, soft-tissue adhesives with excellent adhesion strength and favorable biocompatibility are of great significance in biomedical applications. In this study, an injectable hydrogel tissue adhesive containing adipic acid dihydrazide-modified gelatin (Gel-ADH) and oxidized sodium alginate (OSA) was developed. It was found that this tissue adhesive possessed a uniform structure, appropriate swelling ratio, good injectability, and excellent hemocompatibility and cytocompatibility. The adhesion capacity of the developed adhesive with optimized component and concentration was stronger than that of the commercial adhesive Porcine Fibrin Sealant Kit. All these results suggested that the developed hydrogel was a promising candidate for a soft-tissue adhesive.

Enzyme-Loaded pH-Sensitive Photothermal Hydrogels for Mild-temperature-mediated Combinational Cancer Therapy.

Photothermal therapy (PTT) that utilizes hyperthermia to ablate cancer cells is a promising approach for cancer therapy, while the generated high temperature may lead to damage of surrounding normal tissues and inflammation. We herein report the construction of glucose oxidase (GOx)-loaded hydrogels with a pH-sensitive photothermal conversion property for combinational cancer therapy at mild-temperature. The hydrogels (defined as CAG) were formed via coordination of alginate solution containing pH-sensitive charge-transfer nanoparticles (CTNs) as the second near-infrared (NIR-II) photothermal agents and GOx. In the tumor sites, GOx was gradually released from CAG to consume glucose for tumor starvation and aggravate acidity in tumor microenvironment that could turn on the NIR-II photothermal conversion property of CTNs. Meanwhile, the released GOx could suppress the expression of heat shock proteins to enable mild NIR-II PTT under 1,064 nm laser irradiation. As such, CAG mediated a combinational action of mild NIR-II PTT and starvation therapy, not only greatly inhibiting the growth of subcutaneously implanted tumors in a breast cancer murine model, but also completely preventing lung metastasis. This study thus provides an enzyme loaded hydrogel platform with a pH-sensitive photothermal effect for mild-temperature-mediated combinational cancer therapy.

Oxygen-producing proenzyme hydrogels for photodynamic-mediated metastasis-inhibiting combinational therapy.

Photodynamic therapy (PDT) has provided a promising approach for the treatment of solid tumors, while the therapeutic efficacy is often limited due to the hypoxic tumor microenvironment, resulting in tumor metastasis. Herein, we report an oxygen-producing proenzyme hydrogel (OPeH) with photoactivatable enzymatic activity for PDT enabled metastasis-inhibiting combinational therapy of breast cancer. This OPeH based on alginate is composed of protoporphyrin IX (PpIX) conjugated manganese oxide (MnO2) nanoparticles, which act as both the photosensitizer and oxygen-producing agent, and singlet oxygen (1O2)-responsive proenzyme nanoparticles. In the hypoxic and acidic tumor microenvironment, MnO2 can generate 1O2 to promote PpIX-mediated PDT with an amplified 1O2 generation efficiency, which also triggers the cleavage of 1O2-responsive linkers and cascade activation of proenzymes for cancer cell death. This combinational therapy upon photoactivation not only greatly inhibited the tumor growth, but also suppressed lung metastasis in a mouse xenograft breast tumor model, which is impossible in the case of PDT alone. This study thus provides a proenzyme hydrogel platform with photoactivatable activity for metastasis-inhibiting cancer therapy with high efficacy and safety.

An Oxygen-Enriched Photodynamic Nanospray for Postsurgical Tumor Regression.

Postoperative local recurrence and metastasis are non-negligible challenges in clinical cancer treatment. Photodynamic therapy (PDT) has presented a great potential in preventing cancer recurrence owing to its noninvasiveness and high specificity for local irradiation of tumor sites. However, the application of conventional PDT is often limited by insufficient oxygen supply, making it difficult to achieve high PDT efficacy. Herein, we combined liposomes with photosensitizer indocyanine green (ICG) and perfluorooctyl bromide (PFOB) to develop a new oxygen-enriched photodynamic nanospray (Lip-PFOB-ICG) for cancer postoperative treatment. The Lip-PFOB-ICG not only has good biocompatibility but also enhanced the PDT effect under near-infrared light. More importantly, PFOB can continuously absorb oxygen, thus improving the collision energy transfer between the ICG photosensitizer and oxygen, and significantly inhibit local tumor recurrence in the subcutaneous tumor recurrence model. This oxygen-enriched photodynamic nanospray strategy may open up new avenues for effective postoperative cancer therapy in the clinic.

Identification of a robust subpathway-based signature for acute myeloid leukemia prognosis using an miRNA integrated strategy.

Acute myeloid leukemia (AML) is a heterogeneous disease, and survival signatures are urgently needed to better monitor treatment. MiRNAs displayed vital regulatory roles on target genes, which was necessary involved in the complex disease. We therefore examined the expression levels of miRNAs and genes to identify robust signatures for survival benefit analyses. First, we reconstructed subpathway graphs by embedding miRNA components that were derived from low-throughput miRNA-gene interactions. Then, we randomly divided the data sets from The Cancer Genome Atlas (TCGA) into training and testing sets, and further formed 100 subsets based on the training set. Using each subset, we identified survival-related miRNAs and genes, and identified survival subpathways based on the reconstructed subpathway graphs. After statistical analyses of these survival subpathways, the most robust subpathways with the top three ranks were identified, and risk scores were calculated based on these robust subpathways for AML patient prognoses. Among these robust subpathways, three representative subpathways, path: 05200_10 from Pathways in cancer, path: 04110_20 from Cell cycle, and path: 04510_8 from Focal adhesion, were significantly associated with patient survival in the TCGA training and testing sets based on subpathway risk scores. In conclusion, we performed integrated analyses of miRNAs and genes to identify robust prognostic subpathways, and calculated subpathway risk scores to characterize AML patient survival.