Facile fabrication of hyaluronated starch nanogels for efficient docetaxel delivery

In this study, we designed and synthesized polysaccharidic nanogels comprising starch cross-linked with hyaluronic acid. These hyaluronated starch nanogels were prepared by cross-linking primary hydroxyl groups in polysaccharides (starch and hyaluronic acid) and epoxide groups in 1,4-butanediol diglycidyl ether (used as a cross-linking agent). The nanogels take advantage of hyaluronic acid as a specific ligand for CD44 receptors overexpressed on tumors and the hyaluronic acid/starch core as a compartment for the encapsulation of docetaxel (as model antitumor drug). Here, hyaluronic acid can be enzymatically degraded by tumor cell–specific enzyme (e.g. hyaluronidase-1), which could significantly accelerate docetaxel release from the nanogels. Our experimental results demonstrate that the nanogels promote the release of docetaxel content in the presence of hyaluronidase-1 enzyme. As a result, the nanogels selectively inhibited MCF-7 (with CD44 receptor and hyaluronidase-1 enzyme) tumor cell growth in vitro, suggesting their therapeutic potential for efficient tumor ablation.

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Toward Physicochemical and Rheological Characterization of Different Injectable Hyaluronic Acid Dermal Fillers Cross-Linked with Polyethylene Glycol Diglycidyl Ether

Polymers ◽

10.3390/polym13060948 ◽

2021 ◽

Vol 13 (6) ◽

pp. 948

Author(s):

Nicola Zerbinati ◽

Sabrina Sommatis ◽

Cristina Maccario ◽

Maria Chiara Capillo ◽

Giulia Grimaldi ◽

...

Keyword(s):

Hyaluronic Acid ◽

Polyethylene Glycol ◽

Biological Activities ◽

Diglycidyl Ether ◽

Dermal Filler ◽

Cross Linking ◽

Matrix Structure ◽

Dermal Fillers ◽

Rheological Characterization

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used to restore volume, hydration and skin tone in aesthetic medicine. HA fillers differ from each other due to their cross-linking technologies, with the aim to increase mechanical and biological activities. One of the most recent and promising cross-linkers is polyethylene glycol diglycidyl ether (PEGDE), used by the company Matex Lab S.p.A., (Brindisi, Italy) to create the HA dermal filler PEGDE family. Over the last few years, several studies have been performed to investigate the biocompatibility and biodegradability of these formulations, but little information is available regarding their matrix structure, rheological and physicochemical properties related to their cross-linking technologies, the HA content or the degree of cross-linking. (2) Methods: Seven different injectable HA hydrogels were subjected to optical microscopic examination, cohesivity evaluation and rheological characterization in order to investigate their behavior. (3) Results: The analyzed cross-linked dermal fillers showed a fibrous “spiderweb-like” matrix structure, with each medical device presenting different and peculiar rheological features. Except for HA non cross-linked hydrogel 18 mg/mL, all showed an elastic and cohesive profile. (4) Conclusions: The comparative analysis with other literature works makes a preliminary characterization of these injectable medical devices possible.

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Poly(HPMA)–chlorambucil conjugate nanoparticles: facile fabrication and in vitro anti-cancer activity

New Journal of Chemistry ◽

10.1039/d1nj03134a ◽

2021 ◽

Vol 45 (39) ◽

pp. 18544-18551

Author(s):

Guichen Li ◽

Minzhi Zhao ◽

Jia Zhang ◽

Haining Li ◽

Weibing Xu ◽

...

Keyword(s):

Antitumor Effect ◽

Anti Cancer ◽

Facile Fabrication ◽

Cancer Activity ◽

Mcf 7

An acid-sensitive poly(HPMA)–Chl conjugate was developed and its antitumor effect towards HepG2 and MCF-7 cells was evaluated.

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3D Encapsulation Made Easy: A Coaxial-Flow Circuit for the Fabrication of Hydrogel Microfibers Patches

Bioengineering ◽

10.3390/bioengineering6020030 ◽

2019 ◽

Vol 6 (2) ◽

pp. 30 ◽

Cited By ~ 3

Author(s):

Chiara Campiglio ◽

Francesca Ceriani ◽

Lorenza Draghi

Keyword(s):

Hyaluronic Acid ◽

Regenerative Medicine ◽

Closed Loop ◽

Fiber Diameter ◽

Cross Linking ◽

Scaffold Fabrication ◽

Cell Culturing ◽

Viable Cells ◽

Flow Circuit

To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro.

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Biological Assessment of Laser-Synthesized Silicon Nanoparticles Effect in Two-Photon Photodynamic Therapy on Breast Cancer MCF-7 Cells

Nanomaterials ◽

10.3390/nano10081462 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1462

Author(s):

Ahmed Al-Kattan ◽

Lamiaa M. A. Ali ◽

Morgane Daurat ◽

Elodie Mattana ◽

Magali Gary-Bobo

Keyword(s):

Breast Cancer ◽

Photodynamic Therapy ◽

Silicon Nanoparticles ◽

Therapeutic Potential ◽

Light Stimulus ◽

Human Cancer ◽

Biological Assessment ◽

Two Photon ◽

Mcf 7

Driven by their distinctive physiological activities, biological properties and unique theranostic modalities, silicon nanoparticles (SiNPs) are one of the promising materials for the development of novel multifunctional nanoplatforms for biomedical applications. In this work, we assessed the possibility to use laser-synthesized Si NPs as photosensitizers in two-photon excited photodynamic therapy (TPE-PDT) modality. Herein, we used an easy strategy to synthesize ultraclean and monodispersed SiNPs using laser ablation and fragmentation sequences of silicon wafer in aqueous solution, which prevent any specific purification step. Structural analysis revealed the spherical shape of the nanoparticles with a narrow size distribution centered at the mean size diameter of 62 nm ± 0.42 nm, while the negative surface charge of −40 ± 0.3 mV ensured a great stability without sedimentation over a long period of time. In vitro studies on human cancer cell lines (breast and liver) and healthy cells revealed their low cytotoxicity without any light stimulus and their therapeutic potential under TPE-PDT mode at 900 nm with a promising cell death of 45% in case of MCF-7 breast cancer cells, as a consequence of intracellular reactive oxygen species release. Their luminescence emission inside the cells was clearly observed at UV-Vis region. Compared to Si nanoparticles synthesized via chemical routes, which are often linked to additional modules with photochemical and photobiological properties to boost photodynamic effect, laser-synthesized SiNPs exhibit promising intrinsic therapeutic and imaging properties to develop advanced strategy in nanomedicine field.

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Radiation OncologyIn Vitro: Trends to Improve Radiotherapy through Molecular Targets

BioMed Research International ◽

10.1155/2014/461687 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Natália Feofanova ◽

Jony Marques Geraldo ◽

Lídia Maria de Andrade

Keyword(s):

Tumor Cell ◽

Cellular Proliferation ◽

Therapeutic Potential ◽

Molecular Targets ◽

Beneficial Effects ◽

Cell Proliferation And Migration ◽

And Migration ◽

Improve Clinical Outcome ◽

Proliferation And Migration

Much has been investigated to improve the beneficial effects of radiotherapy especially in that case where radioresistant behavior is observed. Beyond simple identification of resistant phenotype the discovery and development of specific molecular targets have demonstrated therapeutic potential in cancer treatment including radiotherapy. Alterations on transduction signaling pathway related with MAPK cascade are the main axis in cancer cellular proliferation even as cell migration and invasiveness in irradiated tumor cell lines; then, for that reason, more studies are in course focusing on, among others, DNA damage enhancement, apoptosis stimulation, and growth factors receptor blockages, showing promisingin vitroresults highlighting molecular targets associated with ionizing radiation as a new radiotherapy strategy to improve clinical outcome. In this review we discuss some of the main molecular targets related with tumor cell proliferation and migration as well as their potential contributions to radiation oncology improvements.

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Hyaluronic Acid Based Hydrogels for Regenerative Medicine Applications

BioMed Research International ◽

10.1155/2015/871218 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 46

Author(s):

Assunta Borzacchiello ◽

Luisa Russo ◽

Birgitte M. Malle ◽

Khadija Schwach-Abdellaoui ◽

Luigi Ambrosio

Keyword(s):

Hyaluronic Acid ◽

Viscoelastic Properties ◽

Structural Parameters ◽

Weight Ratio ◽

Rheological Behaviour ◽

Biological Properties ◽

Cross Linking ◽

In Vitro Tests ◽

The Cross

Hyaluronic acid (HA) hydrogels, obtained by cross-linking HA molecules with divinyl sulfone (DVS) based on a simple, reproducible, and safe process that does not employ any organic solvents, were developed. Owing to an innovative preparation method the resulting homogeneous hydrogels do not contain any detectable residual cross-linking agent and are easier to inject through a fine needle. HA hydrogels were characterized in terms of degradation and biological properties, viscoelasticity, injectability, and network structural parameters. They exhibit a rheological behaviour typical of strong gels and show improved viscoelastic properties by increasing HA concentration and decreasing HA/DVS weight ratio. Furthermore, it was demonstrated that processes such as sterilization and extrusion through clinical needles do not imply significant alteration of viscoelastic properties. Both SANS and rheological tests indicated that the cross-links appear to compact the network, resulting in a reduction of the mesh size by increasing the cross-linker amount. In vitro degradation tests of the HA hydrogels demonstrated that these new hydrogels show a good stability against enzymatic degradation, which increases by increasing HA concentration and decreasing HA/DVS weight ratio. Finally, the hydrogels show a good biocompatibility confirmed by in vitro tests.

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Comparative Physicochemical Analysis among 1,4-Butanediol Diglycidyl Ether Cross-Linked Hyaluronic Acid Dermal Fillers

Gels ◽

10.3390/gels7030139 ◽

2021 ◽

Vol 7 (3) ◽

pp. 139

Author(s):

Nicola Zerbinati ◽

Sabrina Sommatis ◽

Cristina Maccario ◽

Maria Chiara Capillo ◽

Giulia Grimaldi ◽

...

Keyword(s):

Hyaluronic Acid ◽

Medical Devices ◽

Physicochemical Analysis ◽

Diglycidyl Ether ◽

Dermal Filler ◽

Cross Linking ◽

Matrix Structure ◽

Dermal Fillers ◽

Aesthetic Medicine

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous “spiderweb-like” matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application.

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In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189917 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9917

Author(s):

Jesica M. Ramírez-Villalobos ◽

César I. Romo-Sáenz ◽

Karla S. Morán-Santibañez ◽

Patricia Tamez-Guerra ◽

Ramiro Quintanilla-Licea ◽

...

Keyword(s):

Cell Growth ◽

Tumor Cell ◽

Growth Inhibition ◽

Endophytic Fungi ◽

Tumor Cell Growth ◽

Cell Growth Inhibition ◽

Antitumor Effects ◽

Ht 29 ◽

Mcf 7

Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.

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A Cellular Study of Inflammatory Responses in Women with Polycystic Ovary Syndrome as: “An In vitro Model of Anti Breast Tumor Response” Anti-Breast Tumor Response

10.21203/rs.3.rs-16155/v1 ◽

2020 ◽

Author(s):

Fatemeh Rezayat ◽

Mehri Hajiaghaei ◽

Nazanin Ghasemi ◽

Mehrnaz Mesdaghi ◽

Fahimeh Ramezani Tehrani ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Breast Tumor ◽

Mononuclear Cells ◽

Polycystic Ovary ◽

Healthy Controls ◽

Tumor Cell Lines ◽

Tnf Α ◽

Mcf 7

Abstract Background: Although Polycystic Ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age; is unclear whether PCOS increases the risk of subsequent development of, Gynecologic cancers namely breast cancer. The present study we aimed to compare the antitumoral ability of peripheral blood mononuclear cells (PBMCs) of women with PCOS with that of healthy controls using the co-culture system between effector cells and target tumor cell lines. Materials & Methods: PBMCs were isolated from 25 women with PCOS and 25 non hirsute eumenorrheic healthy controls by density gradient centrifugation ficoll. Breast tumor cell lines (MDA-468, MCF-7) were incubated as the two target cells and were cultured adjacent to PBMCs in the transwell co-culture system. Proliferation rate of the effectors cells evaluated by BrdU cell proliferation assay after 48 and 72 hours and T CD3+ lymphocytes were assessed using flow cytometry. TNF-α cytokine production was evaluated in cell culture supernatant by sandwich ELISA technique. Results: After 48 hours incubation with MDA-468 and MCF-7, the mean proliferation score of PBMCs was significantly higher in women with PCOS compared to that of healthy controls (921.04; P=0.021 vs 287.6; P=0.002, respectively). In PCOS women, after 72 hours of incubation, TNF-α concentration was significantly reduced compared to 48-hour cultures (921.04 ± 271.4 pg/dl vs 545.6 ± 151.1 pg/dl at 48 h and 72 h intervals respectively, P<0.05); it was increased in healthy controls. There was no significant difference in CD3+ CD8+ cells between the PCOS group and healthy controls. Conclusion: The ability of PBMCs to produce of TNF-α in women with PCOS decreased gradually; as a result of which they may lack the ability required to form an in vitro efficient antitumor response to breast tumor cell lines. It is assumed that threshold activation of mononuclear cells is reduced in women with PCOS and a low-grade inflammatory condition may provide a positive background for arising myeloid derived suppressor cells (MDSCs).

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