Materials Science and Engineering: C

Effect of RGD content in poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-alt-maleic acid) hydrogels on the expansion of ovarian cancer stem-like cells

The extracellular matrix (ECM) affects cell behaviors, such as survival, proliferation, motility, invasion, and differentiation. The arginine-glycine-aspartic acid (RGD) sequence is present in several ECM proteins, such as fibronectin, collagen type I, fibrinogen, laminin, vitronectin, and osteopontin. It is very critical to develop ECM-like substrates with well-controlled features for the investigation of influence of RGD on the behavior of tumor cells. In this study, poly(ethylene glycol) (PEG)-crosslinked poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)) hydrogels (PEMM) with different RGD contents were synthesized, fully characterized, and established as in vitro culture platforms to investigate the effects of RGD content on cancer stem cell (CSC) enrichment. The morphology, proliferation, and viability of SK-OV-3 ovarian cancer cells cultured on hydrogels with different RGD contents, the expression of CSC markers and malignant signaling pathway-related genes, and drug resistance were systematically evaluated. The cell aggregates formed on the hydrogel surface with a lower RGD content acquired certain CSC-like properties, thus drug resistance was enhanced. In contrast, the drug sensitivity of cells on the higher RGD content surface increased because of less CSC-like properties. However, the presence of RGD in the stiff hydrogels (PEMM2) had less effect on the stemness expression than did its presence in the soft hydrogels (PEMM1). The results suggest that RGD content and matrix stiffness can lead to synergetic effects on the expression of cancer cell stemness and the epithelial-mesenchymal transition (EMT), interleukin-6 (IL-6), and Wnt pathways.

Catalase immobilized antimonene quantum dots used as an electrochemical biosensor for quantitative determination of H2O2 from CA-125 diagnosed ovarian cancer samples

A selective and cost-effective biosensor based on catalase immobilized antimonene quantum dots modified glassy carbon electrode (Cat@AMQDs-GCE) is designed for the first time to determine hydrogen peroxide (H

Electrosprayed nanoparticles of poly(p-dioxanone-co-melphalan) macromolecular prodrugs for treatment of xenograft ovarian carcinoma

Ovarian cancer is considered to be the most fatal reproductive cancers. Melphalan is used to treat ovarian cancer as an intraperitoneal chemotherapy agent. However, elucidating its pharmacokinetic behavior and preparing it for administration are challenging since it undergoes spontaneous hydrolysis. In this study, melphalan is transformed into a macromolecular prodrug by copolymerizing with p-dioxanone. The hydrophobicity of copolymer chains protects melphalan from hydrolysis. Poly(p-dioxanone-co-melphalan; PDCM) is electrosprayed and converted into nanoparticles (PDCM NPs) with diameters of ~300-350 nm to facilitate its intracellular delivery. UPLC-MS and HPLC are applied to verify and monitor the release of melphalan from PDCM NPs. PDCM NPs could suppress the proliferation of SKOV-3 cells. The IC50 of 4.3% melphalan-containing PDCM-3 NP was 70 mg/L, 72 h post administration. These suppression characteristics not only affected by the degradation and then the extracellular release of melphalan from PDCM NPs, but also the uptake via phagocytosis phenomenon in SKOV-3 cells. As revealed by flow cytometry, phagocytosis is a first-order process. Once phagocytosed, PDCM NPs are digested by lysosomes, causing a rapid release of melphalan into the cytoplasm, which ultimately causes suppression of SKOV-3 cell proliferation. Finally, the in vivo antitumor effects of PDCM NPs are verified in xenograft ovarian carcinoma. After a 20-day treatment, the tumor growth rate of the PDCM-3 NP group was (266 ± 178%) which was lower than those in the free melphalan group (367 ± 150%) and control group (648 ± 149%). Besides, significant tissue necrosis and growth suppression were observed in animals administered injections of PDCM NPs. Furthermore, the in vivo tracing results of Nile red-labeled PDCM NPs demonstrated that PDCM-3 NPs might be phagocytosed by macrophages and then taken to adjacent lymph nodes, which is a way of prevention or early treatment of lymphatic metastasis of tumors.

Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer

Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800 nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.

Doxorubicin-loaded functionalized selenium nanoparticles for enhanced antitumor efficacy in cervical carcinoma therapy

Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.