Osteosarcoma Cells Research Articles

Trifluoperazine exerts anti-osteosarcoma effect by inducing mitochondria-dependent apoptosis via AKT/TXNIP signaling pathway

The survival rates for patients with osteosarcoma (OS) have stagnated over the past few decades. It is essential to find new therapies and drugs. A licensed antipsychotic medication called trifluoperazine (TFP) significantly reduces the growth of several cancers. However, the exact molecular pathways of TFP in OS remain to be discovered. Our research revealed that TFP greatly reduced OS cell migration and growth and caused the arrest of G0/G1 cell cycle. Combined with RNA-Seq data and further research, we confirmed that TFP promoted reactive oxygen species (ROS) production by elevating thioredoxin binding protein (TXNIP) expression to induce mitochondria-dependent apoptosis. Interestingly, we first demonstrated that AKT was an upstream regulatory target of TXNIP in OS cells. Dephosphorylation of AKT led to an increase in TXNIP expression, further elucidating the anticancer mechanism of TFP. In vivo, TFP inhibited subcutaneous OS cell proliferation and induced OS cell apoptosis without noticeable side effects. In conclusion, our findings imply that TFP is a potential treatment for OS.

M2 macrophage exosome-derived Apoc1 promotes ferroptosis resistance in osteosarcoma by inhibiting ACSF2 deubiquitination.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. The aim of this study was to investigate the regulatory mechanisms of M2 macrophage exosomes (M2-Exos) in ferroptosis in OS. A mouse model was established to investigate the in vivo role of M2-Exos. We investigated their effects on ferroptosis in OS using erastin, a ferroptosis activator, and deferoxamine mesylate, an iron chelator. In vitro, we investigated whether the Apoc1/Acyl-CoA Synthetase Family Member 2 (ACSF2) axis mediates these effects, using shApoc1 and shACSF2. The mechanisms whereby Apoc1 regulates ACSF2 were examined using cyclohexanone, a protein synthesis inhibitor, and MG132, a proteasomal inhibitor. M2-Exos reversed the inhibitory effects of erastin on OS cells, thus enhancing their viability, migration, invasion, proliferation, and reducing ferroptosis. Apoc1 was highly expressed in M2-Exos, and interfering with this expression reversed the effects of M2-Exos on OS cells. ACSF2 mediated the effects of M2-Exos-derived Apoc1. Apoc1 interacted with ACSF2, which, in turn, interacted with USP40. Apoc1 overexpression increased ACSF2 ubiquitination, promoting its degradation, whereas USP40 overexpression inhibited ACSF2 ubiquitination and promoted its expression. Apoc1 overexpression inhibited ACSF2 binding to USP40. M2-Exos-derived Apoc1 promoted ferroptosis resistance by inhibiting USP40 binding to ACSF2 and promoting ACSF2 ubiquitination and degradation, thus enhancing OS development.

ROR1-AS1: A Meaningful Long Noncoding RNA in Oncogenesis.

Long noncoding RNA (lncRNA) is a non-coding RNA with a length of more than 200 nucleotides, involved in multiple regulatory processes in vivo, and is related to the physiology and pathology of human diseases. An increasing number of experimental results suggest that when lncRNA is abnormally expressed, it results in the development of tumors. LncRNAs can be divided into five broad categories: sense, antisense, bidirectional, intronic, and intergenic. Studies have found that some antisense lncRNAs are involved in a variety of human tumorigenesis. The newly identified ROR1-AS1, which functions as an antisense RNA of ROR1, is located in the 1p31.3 region of the human genome. Recent studies have reported that abnormal expression of lncRNA ROR1-AS1 can affect cell growth, proliferation, invasion, and metastasis and increase oncogenesis and tumor spread, indicating lncRNA ROR1-AS1 as a promising target for many tumor biological therapies. In this study, the pathophysiology and molecular mechanism of ROR1-AS1 in various malignancies are discussed by retrieving the related literature. ROR1-AS1 is a cancer-associated lncRNA, and studies have found that it is either over- or underexpressed in multiple malignancies, including liver cancer, colon cancer, osteosarcoma, glioma, cervical cancer, bladder cancer, lung adenocarcinoma, and mantle cell lymphoma. Furthermore, it has been demonstrated that lncRNA ROR1-AS1 participates in proliferation, migration, invasion, and suppression of apoptosis of cancer cells. Furthermore, lncRNA ROR1-AS1 promotes the development of tumors by up-regulating or downregulating ROR1-AS1 conjugates and various pathways and miR-504, miR-4686, miR-670-3p, and miR-375 sponges, etc., suggesting that lncRNA ROR1-AS1 may be used as a marker in tumors or a potential therapeutic target for a variety of tumors.

A natural protopanaxatriol from Panax notoginseng enhances osteosarcoma sensitivity to ferroptosis via ASCL4 upregulation

Current treatments for osteosarcoma, the most common primary bone cancer, including surgery, radiotherapy, and chemotherapy, are largely ineffective against metastatic and chemo-resistant cases, emphasizing the need for novel therapies. In this study, we investigated (20S)-Protopanaxatriol [(20S)-PPT], a natural product from Panax notoginseng, an herb used both as food and medicine, for its ability to enhance osteosarcoma sensitivity to ferroptosis induced by inducers such as RSL3, ML210, and IKE. Specifically, (20S)-PPT increased lipid peroxidation in osteosarcoma cells exposed to RSL3. This effect was mediated by ACSL4 upregulation, as ACSL4 knockdown reversed (20S)-PPT-sensitized ferroptosis. Importantly, (20S)-PPT significantly reduced tumor growth in xenograft models when combined with IKE. Collectively, our study confirms that combining (20S)-PPT with ferroptosis inducers offers a promising novel strategy for treating osteosarcoma.

The Contribution of the Novel CLTC-VMP1 Fusion Gene to Autophagy Regulation and Energy Metabolism in Cisplatin-Resistant Osteosarcoma.

Osteosarcoma (OS) is a highly malignant tumor, and chemotherapy resistance is a major challenge in the treatment of this disease. This study aims to explore the role of the CLTC-VMP1 gene fusion in the mechanism of chemotherapy resistance in OS and investigate its molecular mechanisms in mediating energy metabolism reprogramming by regulating autophagy and apoptosis balance. Using single-cell transcriptome analysis, the heterogeneity of OS cells and their correlation with resistance to platinum drugs were revealed. Cisplatin-resistant cell lines were established in human OS cell lines for subsequent experiments. Based on transcriptomic analysis, the importance of VMP1 in chemotherapy resistance was confirmed. Lentiviral vectors overexpressing or interfering with VMP1 were used, and it was observed that inhibiting VMP1 could reverse cisplatin resistance, promote cell apoptosis, and inhibit autophagy, as well as mitochondrial respiration and glycolysis. Furthermore, the presence of CLTC-VMP1 gene fusion was validated, and its ability to regulate autophagy and apoptosis balance, promote mitochondrial respiration, and glycolysis was demonstrated. Mouse model experiments further confirmed the promoting effect of CLTC-VMP1 on tumor growth and chemotherapy resistance. In summary, the CLTC-VMP1 gene fusion mediates energy metabolism reprogramming by regulating autophagy and apoptosis balance, which promotes chemotherapy resistance in OS.

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Development and validation of a novel endoplasmic reticulum stress-related lncRNAs signature in osteosarcoma

Osteosarcoma (OS) is a cancerous tumor, and its development is greatly influenced by long non-coding RNA (lncRNA). Endoplasmic reticulum stress (ERS) is an essential biological defense process in cells and contributes to the progression of tumors. However, the exact mechanisms remain elusive. This study aims to develop a signature of lncRNAs associated with ERS in OS. This signature will guide the prognosis prediction and the determination of appropriate treatment strategies. The UCSC Xena database collected transcriptional and clinical data of OS and muscle, after identifying ERS differentially expressed genes, we utilized correlation analysis to determine the endoplasmic reticulum stress lncRNAs (ERLs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were utilized to develop an ERLs signature. To clarify the fundamental mechanisms controlling gene expression in low and high-risk groups, Gene Set Variation Analysis (GSVA) were conducted. In addition, the distinction between the two groups regarding drug sensitivity and immune-related activity was investigated to determine the immunotherapy effects. Utilizing RT-qPCR, the expression of model lncRNAs in OS cell lines was ascertained. The functional analysis of LINC02298 was carried out through in vitro experiments and pan-cancer analysis. This study successfully constructed an ERLs prognostic signature for OS, which comprised 5 lncRNAs (AC023157.3, AL031673.1, LINC02298, LINC02328, SNHG26). The risk signature predicted overall survival in patients with OS and was confirmed by assessing the validation and whole cohorts. Further, it was discovered that individuals classified as high-risk displayed suppressed immune activation, decreased infiltration of immune cells, and decreased responsiveness to immunotherapy. The RT-qPCR showed that the constructed risk prognosis model is reliable. Experimental validation has demonstrated that LINC02298 can promote OS cells’ invasion, migration, and proliferation. In addition, LINC02298 exhibited significant differential expression in many types of cancer. Moreover, LINC02298 is an important biomarker in a variety of tumors. This study established a novel ERLs signature, which successfully predicted the prognosis of OS. The function of LINC02298 in OS was elucidated via in vitro experiments. Therefore, it offers new opportunities for predicting the clinical prognosis of OS and establishes the basis for targeted therapy in OS.

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition

Osteosarcoma (OS) is the most severe bone tumor in children. A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin. These drugs cause acute and chronic side effects, such as infections, thrombocytopenia, neutropenia, DNA damage, and inflammation. Therefore, to identify new therapeutic strategies, effective and with a safety profile, is necessary. The Hedgehog (Hh) signaling pathway involved in tumorigenesis is active in OS. Hh components Patched receptor 1 (PTCH1), Smoothened (SMO), and glioma-associated oncogene homolog transcription factors (GLI1 and GLI2) are overexpressed in OS cell lines and patient samples. Curcumin (CUR)—with antioxidant and anti-cancer properties—downregulates Hh components in cancer, inhibiting progression. This study investigates CUR effects on the MG-63 OS cell line, alone and combined with MTX, to propose a novel therapeutic approach. Our study suggests CUR as a novel therapeutic agent in OS, particularly when combined with MTX. Targeting the Hh signaling pathway, CUR and MTX showed significant pro-apoptotic effects, increasing the BAX/Bcl-2 ratio and total apoptotic cell percentage. They reduced the expression of Hh pathway components (PTCH1, SMO, GLI1, and GLI2), inhibiting OS cell proliferation, survival, and invasion. CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

Assessing sarcoma cell cytoskeleton remodeling in response to varying collagen concentration

Sarcomas, rare malignant tumors of mesenchymal origin, are often underdiagnosed and have face diagnostic ambiguities and limited treatment options. The main objective of this study was to define the nanomechanical and biophysical properties of sarcoma cells, particularly examining how the cytoskeleton's remodeling and related cellular processes such as cell migration and invasion in response to environmental stimuli due to collagen content. Utilizing one murine fibrosarcoma and one osteosarcoma cell line we employed atomic force microscopy, immunostaining, advanced image processing, in vitro cellular assays, and molecular techniques to investigate cells' cytoskeleton remodeling in response to varying collagen concentration. Our study focused on how alterations in collagen content affects the cytoskeletal dynamics and correlate with changes in gene expression profiles relevant to metastasis and an aggressive cancer phenotypes. Our findings indicate that despite their shared classification, fibrosarcoma and osteosarcoma cells display distinct biophysical properties and respond differently to mechanical forces. Notably, this difference in cellular behavior renders mechanical properties a potent novel biomarkers. Furthermore, the metastasis-related identified genes related to metastatic capability, could be potential therapeutic targets. This study highlights the significance of understanding the unique traits of sarcoma cells to improve diagnostic precision and expand therapeutic strategies, for this rare type of cancer.

Tetrahedral Framework Nucleic Acid-Loaded Retinoic Acid Promotes Osteosarcoma Stem Cell Clearance.

Metastatic osteosarcoma is a commonly seen malignant tumor in adolescents, with a five year survival rate of approximately 20% and a lack of treatment options. Osteosarcoma cancer stem cells are considered to be important drivers of the metastasis of osteosarcoma, and therefore their clearance is considered a promising strategy for treating metastatic osteosarcoma. In the relevant literature, retinoic acid (ATRA) is considered effective for eliminating osteosarcoma stem cells, but it has some inherent disadvantages, including poor solubility, difficulty in entering cells, and structural instability. Tetrahedral framework nucleic acids (tFNAs) are a type of nanoparticles that can carry small-molecule drugs into cells to exert therapeutic effects. Therefore, we designed and synthesized a nanoparticle named T-ATRA by using tFNAs to load ATRA and studied its effect in a nude mouse model. T-ATRA is more effective than ATRA in the clearance of osteosarcoma stem cells and in inhibiting osteosarcoma cell metastasis via the Wnt signaling pathway, thus prolonging the survival time of nude mice with osteosarcoma.

Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis

The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS. Yet, romidepsin has noted toxicities in humans and so here we aimed to define the primary mechanisms through which HDAC1/2 mediate OS progression to identify more selective druggable targets/pathways. Microarray and proteomics analyses of romidepsin treated OS cells revealed a significant suppression of neuropilin-1 (NRP1), a known regulator of cancer cell migration and invasion. Silencing of NRP1 significantly reduced OS proliferation, migration, invasion and adhesion in vitro. More strikingly, in vivo, reduced NRP1 expression significantly mitigated the lung metastatic potential of OS in two independent models (K7M2 and SAOS-LM7). Mechanistically, our data point to NRP1 mediating this effect via the down regulation of migration machinery, namely SRC, FAK and ROCK1 expression/activity, that is in part, related to NRP1 interaction with integrin beta 1 (ITGB1). In summary, our data indicate that romidepsin down regulation of NRP1 significantly mitigates the ability of OS cells to seed the lung and establish metastases, and that targeting NRP1 or its effectors with selective inhibitors may be a viable means with which to prevent this deadly aspect of the disease.

Novel platinum nanoclusters (Pt NCs) induce mitochondrial apoptosis and damaging autophagy for the treatment of osteosarcoma—from the perspective of P53 mutation status in different cell lines

This study aimed to investigate the anticancer efficacy and underlying mechanism of novel platinum nanoclusters (Pt NCs) in osteosarcoma cell lines exhibiting distinct P53 expression profiles, namely MG-63 (P53−) and U2-OS (P53+). The findings revealed that Pt NCs exerted an inhibitory effect on proliferation, migration, and colony formation while promoting apoptosis in both MG-63 (P53−) and U2-OS (P53+) cells. The inhibitory effect on the malignant characteristics of MG-63 (P53−) cells was more obvious, indicating that the potential anticancer effect of Pt NCs was not dependent on P53. Animal experiments have substantiated the in vivo anticancer properties of Pt NCs, while also revealing their lower toxicity on cells and tissues. Pt NCs possess the ability to impede cell proliferation by inducing DNA damage and arresting the cell cycle in the G1 phase and possess the ability to promote BAX/Bcl-2/Caspase-3/mitochondrial apoptosis. Pt NCs may promote mitochondrial apoptosis by promoting damaging autophagy, thereby promoting cellular demise. This study has confirmed the P53-independent anticancer impact of Pt NCs on osteosarcoma in vitro and in vivo. Pt NCs may play a therapeutic role in more sensitive MG-63 (P53−) cells by promoting DNA damage to arrest the cell cycle, stimulating BAX/Bcl-2/Caspase-3/mitochondrial apoptosis, and initiating damaging autophagy.

Enhancing radiosensitivity in osteosarcoma via CDKN2C overexpression: A mechanism involving G1 phase arrest mediated by inhibition of CDK4 expression and Thr172 phosphorylation

BackgroundThe limited radiosensitivity of osteosarcoma poses a challenge in applying radiotherapy, necessitating the search for effective radiosensitizing targets. MethodsThe lentiviral vectors were employed to establish CDKN2C-overexpressing (CDKN2C-OE) and CDKN2C-negative control (CDKN2C-NC) HOS and U2OS osteosarcoma cells. Cells were treated with or without irradiation (IR) to assess radiosensitization via viability, proliferation, apoptosis, and cell cycle analysis. A mouse model with subcutaneous tumors from CDKN2C-OE and CDKN2C-NC HOS cells evaluated tumor growth post-IR. Immunohistochemical staining and Western blot analysis were conducted to confirm model establishment and explore mechanisms. ResultsCDKN2C-OE combined with IR inhibited cell viability and proliferation, promoting apoptosis in vitro and inhibiting tumor growth in vivo. CDKN2C-OE inhibited G1 phase progression post-IR by suppressing Cyclin-dependent kinase 4 (CDK4) expression and Thr172 phosphorylation, reducing retinoblastoma protein (RB) phosphorylation at Ser807/811. CDKN2C-OE did not primarily impact the cell cycle by regulating the expression of CDK6 and Cyclin D1. Furthermore, when CDKN2C-OE was combined with IR, the expression of BAX, Caspase-3, and its active cleavage product, cleaved Caspase-3, was upregulated. ConclusionsOur research results indicate that overexpression of CDKN2C enhances radiosensitivity in osteosarcoma through the induction of G1 phase arrest and subsequent apoptosis. G1 phase arrest is mediated by the suppression of CDK4 expression and Thr172 phosphorylation, which consequently affects the expression of phosphorylated RB at the Ser807/811 sites.

Retraction of: miR-627-3p inhibits osteosarcoma cell proliferation and metastasis by targeting PTN.

Retraction of: miR-627-3p inhibits osteosarcoma cell proliferation and metastasis by targeting PTN.

Aucubin Induces Apoptotic Cell Death Through Caspase-dependent Pathways in Human Osteosarcoma MG-63 Cells

Background Osteosarcomas (OSs) are predominantly generated by mesenchymal cells, which commonly develop in the distal and upper regions of the bones. OS has high mortality rates and treatment failures, mostly due to the presence of lung metastases. Purpose The present work aimed to scrutinize the anticancer potentials of aucubin against OS human osteosarcoma (MG-63) cells. Methods The proliferation of the control and aucubin-treated MG-63 cells was studied by an XTT assay. Various fluorescent staining assays were done to assess the endogenous reactive oxygen species (ROS) accumulation and apoptosis in the aucubin-treated MG-63 cells. The caspase-3, -8, and -9 activities were investigated using the assay kits. Results The XTT assay results confirmed that the aucubin treatment considerably reduced the MG-63 cells. The findings of the various fluorescent staining assays evidenced that the aucubin treatment remarkably promoted endogenous ROS accumulation and apoptosis in the OS cells. The caspase activities were also improved in the OS cells after the aucubin treatment. Conclusion The results of this work show that aucubin treatments inhibit cell proliferation and trigger apoptosis in MG-63 cells, suggesting its potential as a promising anticancer agent. These findings will facilitate the future development of aucubin as a talented anticancer agent to treat OS.

Comprehensive Cell Biological Investigation of Cytochalasin B Derivatives with Distinct Activities on the Actin Network.

In search of a more comprehensive structure-activity relationship (SAR) regarding the inhibitory effect of cytochalasin B (2) on actin polymerization, a virtual docking of 2 onto monomeric actin was conducted. This led to the identification of potentially important functional groups of 2 (i.e., the NH group of the isoindolone core (N-2) and the hydroxy groups at C-7 and C-20) involved in interactions with the residual amino acids of the binding pocket of actin. Chemical modifications of 2 at positions C-7, N-2, and C-20 led to derivatives 3-6, which were analyzed for their bioactivities. Compounds 3-5 exhibited reduced or no cytotoxicity in murine L929 fibroblasts compared to that of 2. Moreover, short- and long-term treatments of human osteosarcoma cells (U-2OS) with 3-6 affected the actin network to a variable extent, partially accompanied by the induction of multinucleation. Derivatives displaying acetylation at C-20 and N-2 were subjected to slow intracellular conversion to highly cytotoxic 2. Together, this study highlights the importance of the hydroxy group at C-7 and the NH function at N-2 for the potency of 2 on the inhibition of actin polymerization.

Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours. The viability of the cells derived from osteosarcoma, chondrosarcoma, and giant cell tumours was significantly reduced in the presence of 45S5-BG. In contrast, the viability of non-malignant osteoblast-like cells, chondrocytes, and bone marrow-derived stromal cells was not or only slightly affected. While alterations to the particle surface induced by heat treatment, acid etching, or incubation in a simulated body fluid had only minor effects on cytotoxicity, reducing the particle size or sintering the material significantly improved the cytotoxic effect of 45S5-BG. Further, using a chicken chorioallantoic membrane assay, the co-transplantation of 45S5-BG resulted in a significant reduction in tumour formation in vivo. Given the known positive effects of BGs on bone regeneration, our findings suggest that 45S5-BG holds great potential for the development of new and effective bone tumour therapies, with minimal side effects on non-malignant cells and simultaneous contribution to bone healing.

Multifunctional zinc oxide loaded stearic acid surfaces on biodegradable magnesium WE43 alloy with hydrophobic, self-cleaning and biocompatible attributes

Biodegradable Mg alloys are one of the most promising materials for implant applications, for which the widespread use is hampered by rapid degradation in physiological environment. The present study explores the development of a novel zinc-oxide (ZnO) loaded stearic acid (SA) coating on medical grade WE43 alloy using a facile, and environment-friendly technique for promising biomaterial surface applications. Morphology and chemical analyses reveal the development of a layered coating surface with uniformly dispersed ZnO nanoparticles in SA matrix. The developed coating exhibits hydrophobic performance (contact angle of 135°) along with the retainment of hydrophobicity under varying chemical (acidic pH of 1 and basic pH of 13) and mechanical (post scratch testing and peel-off studies) conditions. The observed surface water repellency facilitates self-cleaning performance pointing towards its efficacy against potential biofilm formation. The developed coating demonstrates superior resistance against surface degradation during immersion studies in phosphate buffer saline solution (pH = 7.4) and better cell viability with MG-63 (human osteosarcoma) cell line. The approach presented here sets a platform for the development of efficient coatings on biodegradable WE43 alloys surfaces for potential biomaterial technologies.

A combination of lymphatic drug delivery of anti-CTLA-4 antibody and local radiotherapy for solid-tumor treatment.

The combination of radiotherapy and immunotherapy is a promising approach that has been shown in clinical trials to improve significantly survival and response rates compared with monotherapy against solid tumor. Since anti-CTLA-4 antibodies block immunosuppressive signals mainly in the lymph nodes (LNs), efficient drug delivery to the lymphatic system is desirable. However, the immune checkpoint inhibitors, especially anti-CTLA-4 are currently administered intravenously (i.v.), resulting in limited efficacy in controlling solid tumor and inhibiting metastases, and the method of administration has not been optimized. Here, we show that a combination of local radiotherapy and administration of anti-CTLA-4 antibodies using a lymphatic drug delivery system (LDDS) suppresses solid tumor and metastases. We compared the efficacy of LDDS-based immunotherapy or radioimmunotherapy with i.v. administration in a solid-tumor model created by subcutaneous inoculation into LN-swollen mice with osteosarcoma cells. Tumor-bearing mice were divided into various groups (no treatment, immunotherapy [i.v. or LDDS], radiotherapy, and radioimmunotherapy [i.v. or LDDS]) and were observed for 28 days. Immunotherapy was administered with a cumulative dose of 10 mg/kg of anti-CTLA-4 monoclonal antibody, and radiotherapy was administered with a cumulative 8 Gy of fractionated X-ray irradiation. For immunotherapy alone, LDDS provided slight tumor growth inhibition but did not inhibit distant metastasis. For radioimmunotherapy, however, tumor growth was delayed and distant metastasis was suppressed compared with radiotherapy alone. In particular, the LDDS group achieved a high tumor-suppressive effect with T cell-mediated immune activity, indicating the efficacy of LDDS in radioimmunotherapy.