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Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (-25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.
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Objective To discuss the feasibility and clinical outcomes of mini-open reduction through lateral deltoid muscle and locking plate fixation in treatment of proximal humeral fractures.Methods A retrospective study was carried out on 39 patients with proximal humeral fractures treated with mini-open reduction through lateral deltoid muscle and locking plate fixation from September 2012 to September 2015.There were 7 males and 32 females,with a mean age of 66.8 years (range,33-86 years).According to the Neer's classification system,there were 26 patients with two-part fracture and 13 with three-part fracture.visual analogue scale (VAS),Constant-Murley shoulder score,time of bone healing and complications were evaluated for all patients.Results All patients were followed up for 12-48 months (mean,21.3 months).All fractures were proved to be bone healing with duration of (12.0 ± 2.7) weeks.The VAS was improved from preoperative (5.7 ± 1.0) points to (0.9 ± 0.6) points at the final follow-up (P ＜ 0.05).The Constant-Murley shoulder score was increased from preoperative (42.3 ±5.1) points to (89.2± 2.5)points at the final follow-up (P ＜ 0.05).Ranges of shoulder motion were improved with satisfactions.There were no complications like axillary nerve injury,loss of reduction,nonunion or humeral head necrosis.Conclusion For proximal humeral fractures,the miniopen reduction through lateral deltoid muscle and locking plate fixation has advantages of minimal invasion,excellent shoulder function,high rate of bone healing and low incidence of complications.
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<p><b>OBJECTIVE</b>To investigate the effect of co-expression of bone morphogenetic protein 2 (BMP2) and Sox9 on chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro and provide experimental evidence for tissue engineering of cartilage.</p><p><b>METHODS</b>Mouse embryonic bone marrow MSC C3H10T1/2 cells were infected with recombinant adenovirus expressing BMP2, Sox9 and green fluorescent protein (GFP) for 3-14 days, with cells infected with the adenovirus carrying GFP gene as the control. The mRNA expression of the markers of chondrogenic differentiation, including collagen type II (Col2a1), aggrecan (ACAN), and collagen type X (Col10a1), were determined by real-time PCR. Alcian blue staining was used for quantitative analysis of sulfated glycosaminoglycan in the cellular matrix. The expression of Col2a1 protein was assayed by immunohistochemical staining and Western blot analysis.</p><p><b>RESULTS</b>Adenovirus-mediated BMP2 expression induced chondrogenic differentiation of C3H10T1/2 cells. Overexpression of Sox9 effectively enhanced BMP2-induced expression of the chondrogenic markers Col2a1, aggrecan and Col10a1 mRNAs, and promoted the synthesis of sulfated glycosaminoglycan and Col2a1 protein in C3H10T1/2 cells.</p><p><b>CONCLUSION</b>Co-expression of BMP2 and Sox9 can promote chondrogenic differentiation of MSCs in vitro, which provides a new strategy for tissue engineering of cartilage.</p>