The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment, and thus calls for the development of new therapeutic options. Here, we reported a bone-targeted protein nanomedicine for this purpose. Saporin, a toxin protein, was co-assembled with a boronated polymer for intracellular protein delivery, and the formed nanoparticles were further coated with an anionic polymer poly (aspartic acid) to shield the positive charges on nanoparticles and provide the bone targeting function. The prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo, and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular acidity. The boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells, exerting the anticancer activity of saporin by inactivation of ribosomes. As a result, the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose, and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in vivo. This study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.

Biofilm-associated infections are difficult to treat in the clinics because the bacteria embedded in biofilm are ten to thousand times more resistant to traditional antibiotics than planktonic ones. Here, a smart hydrogel comprised of aminoglycoside antibiotics, pectinase, and oxidized dextran was developed to treat local biofilm-associated infections. The primary amines on aminoglycosides and pectinase were reacted with aldehyde groups on oxidized dextran via a pH-sensitive Schiff base linkage to form the hydrogel. Upon bacterial infection, the increased acidity triggers the release of both pectinase and aminoglycoside antibiotics. The released pectinase efficiently degrades extracellular polysaccharides surrounding the bacteria in biofilm, and thus greatly sensitizes the bacteria to aminoglycosides. The smart hydrogel efficiently eradicated biofilms and killed the embedded bacteria both n tvitro and in vivo. This study provides a promising strategy for the treatment of biofilm-associated infections.

Postmenopausal osteoporosis (PMOP) and sarcopenia are common diseases that predominantly affect postmenopausal women. In the occurrence and development of these two diseases, they are potentially pathologically connected with each other at various molecular levels. However, the application of metabolomics in sarco-osteoporosis and the metabolic rewiring happening throughout the estrogen loss-replenish process have not been reported. To investigate the metabolic alteration of sarco-osteoporosis and the possible therapeutical effects of estradiol, 24 mice were randomly divided into sham surgery, ovariectomy (OVX), and estradiol-treated groups. Three-dimensional reconstructions and histopathology examination showed significant bone loss after ovariectomy. Estrogen can well protect against OVX-induced bone loss deterioration. UHPLC-Q-TOF/MS was preformed to profile semi- polar metabolites of skeletal muscle samples from all groups. Metabolomics analysis revealed metabolic rewiring occurred in OVX group, most of which can be reversed by estrogen supplementation. In total, 65 differential metabolites were identified, and pathway analysis revealed that sarco-osteoporosis was related to the alterations in purine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tryptophan metabolism, histidine metabolism, oxidative phosphorylation, and thermogenesis, which provided possible explanations for the metabolic mechanism of sarco-osteoporosis. This study indicates that an UHPLC-Q-TOF/MS-based metabolomics approach can elucidate the metabolic reprogramming mechanisms of sarco-osteoporosis and provide biological evidence of the therapeutical effects of estrogen on sarco-osteoporosis.

Purpose: Photothermal therapy (PTT) is promising for the treatment of tumors due to its advantages including minimally invasive, easy implementation and selective localized treatment. However, single PTT suffers from several limitations, such as constrained light penetration and low delivery efficiency, typically leading to heterogeneous heating and incomplete elimination of cancer cells. Therefore, combination of PTT with other therapies, eg, chemotherapy is desirable in order to achieve synergistic effects in cancer treatment. Methods: Here, we designed a new type of TCPP-Iso combined nanoparticle for synergetic therapy for breast cancer. Specifically, photothermal agent tetra(4-carboxyphenyl) porphine (TCPP) and anti-cancer drug isoliensinine (Iso) were encapsulated in PEG-b-PLGA polymeric nanoparticles through a precipitation process. Results: The obtained NPs displayed well-controlled size and high stability over time. Tuning TCPP-Iso/polymer ratio, or total concentration of drug and polymers led to increased hydrodynamic radius of NPs from 65 to 108 nm without disturbing the narrow size distribution. Besides, the formed NPs showed a consequently cumulative release of TCPP and of Iso. The temperature elevation ability of both TCPP NPs and TCPP-Iso NPs was TCPP-concentration dependent. Solutions of TCPP NPs that contained equivalent amount of TCPP with respect to TCPP-Iso NPs, presented the same trend and exhibited non-obvious difference in temperature elevation under certain laser power. The viability of MDA-MB-231 cells treated with TCPP-Iso NPs could be inhibited effectively at a relatively mild temperature (42– 43°C) compared to the other groups, which may minimize heat damage to the surrounding healthy tissues. Conclusion: The results indicate that the TCPP-Iso combined NPs showed hardly any toxicity to normal tissue cell line, but displayed an efficient synergistic effect for killing cancer cells under laser irradiation. Our study demonstrates that the successful combination of TCPP and Iso realized a synergistic therapy effect at a relatively mild temperature, and the insights obtained here shall be helpful for designing new combined PTT agents for cancer treatment.

Solitary fibrous tumors are rare neoplasms that originate from mesenchymal tissues and have been found to occur in any site, including the spine and liver. Although most of solitary fibrous tumors have benign features, only 10–20% are malignant and prone to metastasis. No previous reports have described the malignant and metastatic Solitary fibrous tumor arising in both of the liver and thoracic vertebrae. In this article, we present the case of a 60-year-old woman who underwent gross total resection of a meningeal tumor in 2007. She presented 10 years later with a thoracic vertebral mass that caused relentless pain and a lesion in the right lobe of liver. She underwent marginal excision of the T3 tumor with T2-4 pedicular screw fixation in March 2017, then right hemi-hepatectomy was performed to remove the liver lesion in June 2017. Both of the lesions were confirmed to be a metastatic and malignant tumor after surgery. The literature lacks randomized controlled trials and large studies that define the natural history of malignant solitary fibrous tumors and recommendations of precise management plan for the disease. However, the best choice for treatment is gross total resection, which probably provide the optimal treatment to achieve long-term disease-free survival.