Editorial

3 pages, 202 KiB

Open AccessEditorial

Nanoparticles for Bio-Medical Applications

by Miguel Gisbert-Garzarán and María Vallet-Regí

Nanomaterials 2022, 12(7), 1189; https://doi.org/10.3390/nano12071189 - 02 Apr 2022

Cited by 5 | Viewed by 1837

The Special Issue of Nanomaterials “Nanoparticles for Biomedical Applications” highlights the use of different types of nanoparticles for biomedical applications, including magnetic nanoparticles, mesoporous carbon nanoparticles, mesoporous bioactive glass nanoparticles, and mesoporous silica nanoparticles [...] Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

Research

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16 pages, 4020 KiB

Open AccessArticle

Incorporation of Superparamagnetic Iron Oxide Nanoparticles into Collagen Formulation for 3D Electrospun Scaffolds

by Manuel Estévez, Giorgia Montalbano, Alvaro Gallo-Cordova, Jesús G. Ovejero, Isabel Izquierdo-Barba, Blanca González, Clarissa Tomasina, Lorenzo Moroni, María Vallet-Regí, Chiara Vitale-Brovarone and Sonia Fiorilli

Nanomaterials 2022, 12(2), 181; https://doi.org/10.3390/nano12020181 - 06 Jan 2022

Cited by 15 | Viewed by 2694

Abstract

Nowadays, there is an ever-increasing interest in the development of systems able to guide and influence cell activities for bone regeneration. In this context, we have explored for the first time the combination of type-I collagen and superparamagnetic iron oxide nanoparticles (SPIONs) to [...] Read more.

Nowadays, there is an ever-increasing interest in the development of systems able to guide and influence cell activities for bone regeneration. In this context, we have explored for the first time the combination of type-I collagen and superparamagnetic iron oxide nanoparticles (SPIONs) to design magnetic and biocompatible electrospun scaffolds. For this purpose, SPIONs with a size of 12 nm were obtained by thermal decomposition and transferred to an aqueous medium via ligand exchange with dimercaptosuccinic acid (DMSA). The SPIONs were subsequently incorporated into type-I collagen solutions to prove the processability of the resulting hybrid formulation by means of electrospinning. The optimized method led to the fabrication of nanostructured scaffolds composed of randomly oriented collagen fibers ranging between 100 and 200 nm, where SPIONs resulted distributed and embedded into the collagen fibers. The SPIONs-containing electrospun structures proved to preserve the magnetic properties of the nanoparticles alone, making these matrices excellent candidates to explore the magnetic stimuli for biomedical applications. Furthermore, the biological assessment of these collagen scaffolds confirmed high viability, adhesion, and proliferation of both pre-osteoblastic MC3T3-E1 cells and human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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14 pages, 1575 KiB

Open AccessArticle

Biodistribution of Mesoporous Carbon Nanoparticles via Technetium-99m Radiolabelling after Oral Administration to Mice

by Maria Mamai, Dimitra Giasafaki, Evangelia-Alexandra Salvanou, Georgia Charalambopoulou, Theodore Steriotis and Penelope Bouziotis

Nanomaterials 2021, 11(12), 3260; https://doi.org/10.3390/nano11123260 - 30 Nov 2021

Cited by 5 | Viewed by 2055

Abstract

The use of ordered mesoporous matrices, and in particular carbon-based mesoporous nanoparticles has shown great potential towards enhancing the bioavailability of orally administered drugs. Nevertheless, elucidation of the in vivo absorption, distribution, and excretion of such carriers is essential for understanding their behaviour, [...] Read more.

The use of ordered mesoporous matrices, and in particular carbon-based mesoporous nanoparticles has shown great potential towards enhancing the bioavailability of orally administered drugs. Nevertheless, elucidation of the in vivo absorption, distribution, and excretion of such carriers is essential for understanding their behaviour, and radiolabelling provides a very useful way to track their occurrence inside the body. In this work, uniform spherical CMK-1-type ordered mesoporous carbon nanoparticles have been radiolabelled with Technetium-99m (^99mTc) and traced after oral administration to mice. Ex vivo biodistribution studies showed that the radiolabelled nanoparticles accumulated almost exclusively in the gastrointestinal tract; complete elimination of the radiotracer was observed within 24 h after administration, with practically no uptake into other main organs. These findings along with the results from in vitro stability studies indicate that the spherical carbon nanoparticles examined could be safely used as drug carriers with minimal side effects, but also support the great value of radiolabelling methods for monitoring the particles’ behaviour in vivo. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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19 pages, 5971 KiB

Open AccessArticle

Atomic Resolution Electron Microscopy: A Key Tool for Understanding the Activity of Nano-Oxides for Biomedical Applications

by Alberto Azor-Lafarga, Isabel Gómez-Recio, M. Luisa Ruiz-González and José M. González-Calbet

Nanomaterials 2021, 11(8), 2073; https://doi.org/10.3390/nano11082073 - 16 Aug 2021

Cited by 1 | Viewed by 2198

Abstract

Transition metal oxides constitute one of the most fruitful sources of materials with continuously increasing potential applications prompted by the expectations derived from the reduction of the particle size. The recent advances in transmission electron microscopy, because of the development of lenses, have [...] Read more.

Transition metal oxides constitute one of the most fruitful sources of materials with continuously increasing potential applications prompted by the expectations derived from the reduction of the particle size. The recent advances in transmission electron microscopy, because of the development of lenses, have made it possible to reach atomic resolution, which can provide answers regarding the performance of the transition metal nano-oxides. This critical information is related not only to the ability to study their microstructural characteristics but also their local composition and the oxidation state of the transition metal. Exploring these features is a well-known task in nano-oxides for energy and electronic technologies, but they are not so commonly used for elucidating the activity of these oxides for biomedical applications. Nevertheless, the identification at the atomic level of a certain dopant or the unambiguous determination of the oxidation state of a transition metal in a nano-oxide can be important questions to be answered in a certain biomedical application. In this work, we provide several examples in transition metal nano-oxides to show how atomic-resolution electron microscopy can be a key tool for its understanding. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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14 pages, 5544 KiB

Open AccessArticle

Combination of Selective Etching and Impregnation toward Hollow Mesoporous Bioactive Glass Nanoparticles

by Nurshen Mutlu, Ana Maria Beltrán, Qaisar Nawaz, Martin Michálek, Aldo R. Boccaccini and Kai Zheng

Nanomaterials 2021, 11(7), 1846; https://doi.org/10.3390/nano11071846 - 16 Jul 2021

Cited by 10 | Viewed by 3082

Abstract

In this study, binary SiO₂-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO₂ NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed [...] Read more.

In this study, binary SiO₂-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO₂ NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO₂ NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO₂ NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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14 pages, 40094 KiB

Open AccessArticle

Sustained In-Vivo Release of Triptorelin Acetate from a Biodegradable Silica Depot: Comparison to Pamorelin^® LA

by Ari-Pekka Forsback, Panu Noppari, Jesse Viljanen, Jari Mikkola, Mika Jokinen, Lasse Leino, Simon Bjerregaard, Camilla Borglin and Janet Halliday

Nanomaterials 2021, 11(6), 1578; https://doi.org/10.3390/nano11061578 - 16 Jun 2021

Cited by 8 | Viewed by 4292

Abstract

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size [...] Read more.

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin^® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin^® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin^® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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16 pages, 32895 KiB

Open AccessArticle

Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells

by Vicente Candela-Noguera, Gema Vivo-Llorca, Borja Díaz de Greñu, María Alfonso, Elena Aznar, Mar Orzáez, María Dolores Marcos, Félix Sancenón and Ramón Martínez-Máñez

Nanomaterials 2021, 11(5), 1298; https://doi.org/10.3390/nano11051298 - 14 May 2021

Cited by 6 | Viewed by 2810

Abstract

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of [...] Read more.

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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15 pages, 5321 KiB

Open AccessArticle

Highly Sensitive Electrochemical Biosensor Using Folic Acid-Modified Reduced Graphene Oxide for the Detection of Cancer Biomarker

by Renu Geetha Bai, Kasturi Muthoosamy, Rando Tuvikene, Huang Nay Ming and Sivakumar Manickam

Nanomaterials 2021, 11(5), 1272; https://doi.org/10.3390/nano11051272 - 12 May 2021

Cited by 25 | Viewed by 3702

Abstract

The detection of cancer biomarkers in the early stages could prevent cancer-related deaths significantly. Nanomaterials combined with biomolecules are extensively used in drug delivery, imaging, and sensing applications by targeting the overexpressed cancer proteins such as folate receptors (FRs) to control the disease [...] Read more.

The detection of cancer biomarkers in the early stages could prevent cancer-related deaths significantly. Nanomaterials combined with biomolecules are extensively used in drug delivery, imaging, and sensing applications by targeting the overexpressed cancer proteins such as folate receptors (FRs) to control the disease by providing earlier treatments. In this investigation, biocompatible reduced graphene oxide (rGO) nanosheets combined with folic acid (FA)-a vitamin with high bioaffinity to FRs-is utilized to develop an electrochemical sensor for cancer detection. To mimic the cancer cell environment, FR-β protein is used to evaluate the response of the rGO-FA sensor. The formation of the rGO-FA nanocomposite was confirmed through various characterization techniques. A glassy carbon (GC) electrode was then modified with the obtained rGO-FA and analyzed via differential pulse voltammetry (DPV) for its specific detection towards FRs. Using the DPV technique, the rGO-FA-modified electrode exhibited a limit of detection (LOD) of 1.69 pM, determined in a linear concentration range from 6 to 100 pM. This excellent electrochemical performance towards FRs detection could provide a significant contribution towards future cancer diagnosis. Moreover, the rGO-FA sensing platform also showed excellent specificity and reliability when tested against similar interfering biomolecules. This rGO-FA sensor offers a great promise to the future medical industry through its highly sensitive detection towards FRs in a fast, reliable, and economical way. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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21 pages, 6351 KiB

Open AccessArticle

Specific Absorption Rate Dependency on the Co²⁺ Distribution and Magnetic Properties in Co_xMn_1-xFe₂O₄ Nanoparticles

by Venkatesha Narayanaswamy, Imaddin A. Al-Omari, Aleksandr S. Kamzin, Bashar Issa, Huseyin O. Tekin, Hafsa Khourshid, Hemant Kumar, Ambresh Mallya, Sangaraju Sambasivam and Ihab M. Obaidat

Nanomaterials 2021, 11(5), 1231; https://doi.org/10.3390/nano11051231 - 07 May 2021

Cited by 8 | Viewed by 2161

Abstract

Mixed ferrite nanoparticles with compositions Co_xMn_1-xFe₂O₄ (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) were synthesized by a simple chemical co-precipitation method. The structure and morphology of the nanoparticles were obtained by X-ray diffraction [...] Read more.

Mixed ferrite nanoparticles with compositions Co_xMn_1-xFe₂O₄ (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) were synthesized by a simple chemical co-precipitation method. The structure and morphology of the nanoparticles were obtained by X-ray diffraction (XRD), transmission electron microscope (TEM), Raman spectroscopy, and Mössbauer spectroscopy. The average crystallite sizes decreased with increasing x, starting with 34.9 ± 0.6 nm for MnFe₂O₄ (x = 0) and ending with 15.0 ± 0.3 nm for CoFe₂O₄ (x = 1.0). TEM images show an edge morphology with the majority of the particles having cubic geometry and wide size distributions. The mixed ferrite and CoFe₂O₄ nanoparticles have an inverse spinel structure indicated by the splitting of A_1g peak at around 620 cm⁻¹ in Raman spectra. The intensity ratios of the A_1g(1) and A_1g(2) peaks indicate significant redistribution of Co²⁺ and Fe³⁺ cations among tetrahedral and octahedral sites in the mixed ferrite nanoparticles. Magnetic hysterics loops show that all the particles possess significant remnant magnetization and coercivity at room temperature. The mass-normalized saturation magnetization is highest for the composition with x = 0.8 (67.63 emu/g), while CoFe₂O₄ has a value of 65.19 emu/g. The nanoparticles were PEG (poly ethylene glycol) coated and examined for the magneto thermic heating ability using alternating magnetic field. Heating profiles with frequencies of 333.45, 349.20, 390.15, 491.10, 634.45, and 765.95 kHz and 200, 250, 300, and 350 G field amplitudes were obtained. The composition with x = 0.2 (Co_0.2Mn_0.8Fe₂O₄) with saturation magnetization 57.41 emu/g shows the highest specific absorption rate (SAR) value of 190.61 W/g for 10 mg/mL water dispersions at a frequency of 765.95 kHz and 350 G field strength. The SAR values for the mixed ferrite and CoFe₂O₄ nanoparticles increase with increasing concentration of particle dispersions, whereas for MnFe₂O₄, nanoparticles decrease with increasing the concentration of particle dispersions. SARs obtained for Co_0.2Mn_0.8Fe₂O₄ and CoFe₂O₄ nanoparticles fixed in agar ferrogel dispersions at frequency of 765.95 kHz and 350 G field strength are 140.35 and 67.60 W/g, respectively. This study shows the importance of optimizing the occupancy of Co²⁺ among tetrahedral and octahedral sites of the spinel system, concentration of the magnetic nanoparticle dispersions, and viscosity of the surrounding medium on the magnetic properties and heating efficiencies. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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15 pages, 7649 KiB

Open AccessArticle

In Vitro Biocompatibility Assessment of Nano-Hydroxyapatite

by Rafaela-Maria Kavasi, Catarina C. Coelho, Varvara Platania, Paulo A. Quadros and Maria Chatzinikolaidou

Nanomaterials 2021, 11(5), 1152; https://doi.org/10.3390/nano11051152 - 28 Apr 2021

Cited by 45 | Viewed by 4342

Abstract

Hydroxyapatite (HA) is an important component of the bone mineral phase. It has been used in several applications, such as bone regenerative medicine, tooth implants, drug delivery and oral care cosmetics. In the present study, three different batches of a commercial nanohydroxyapatite (nHA) [...] Read more.

Hydroxyapatite (HA) is an important component of the bone mineral phase. It has been used in several applications, such as bone regenerative medicine, tooth implants, drug delivery and oral care cosmetics. In the present study, three different batches of a commercial nanohydroxyapatite (nHA) material were physicochemically-characterized and biologically-evaluated by means of cytotoxicity and genotoxicity using appropriate cell lines based on well-established guidelines (ISO10993-5 and OECD 487). The nHAs were characterized for their size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM) and were found to have a rod-like shape with an average length of approximately 20 to 40 nm. The nanoparticles were cytocompatible according to ISO 10993-5, and the in vitro micronucleus assay showed no genotoxicity to cells. Internalization by MC3T3-E1 cells was observed by TEM images, with nHA identified only in the cytoplasm and extracellular space. This result also validates the genotoxicity since nHA was not observed in the nucleus. The internalization of nHA by the cells did not seem to affect normal cell behavior, since the results showed good biocompatibility of these nHA nanoparticles. Therefore, this work is a relevant contribution for the safety assessment of this nHA material. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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17 pages, 4027 KiB

Open AccessArticle

Effects of Ipriflavone-Loaded Mesoporous Nanospheres on the Differentiation of Endothelial Progenitor Cells and Their Modulation by Macrophages

by Laura Casarrubios, Alberto Polo-Montalvo, María Concepción Serrano, María José Feito, María Vallet-Regí, Daniel Arcos and María Teresa Portolés

Nanomaterials 2021, 11(5), 1102; https://doi.org/10.3390/nano11051102 - 24 Apr 2021

Cited by 12 | Viewed by 2312

Abstract

Angiogenic biomaterials are designed to promote vascularization and tissue regeneration. Nanoparticles of bioactive materials loaded with drugs represent an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. In this work, porcine endothelial progenitor cells (EPCs), essential for blood vessel [...] Read more.

Angiogenic biomaterials are designed to promote vascularization and tissue regeneration. Nanoparticles of bioactive materials loaded with drugs represent an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. In this work, porcine endothelial progenitor cells (EPCs), essential for blood vessel formation, were isolated and characterized to evaluate the in vitro effects of unloaded (NanoMBGs) and ipriflavone-loaded nanospheres (NanoMBG-IPs), which were designed to prevent osteoporosis. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) was studied in EPCs under different culture conditions: (a) treatment with NanoMBGs or NanoMBG-IPs, (b) culture with media from basal, M1, and M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, (c) coculture with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and (d) coculture with M2d angiogenic macrophages. The endocytic mechanisms for nanosphere incorporation by EPCs were identified using six different endocytosis inhibitors. The results evidence the great potential of these nanomaterials to enhance VEGFR2 expression and angiogenesis, after intracellular incorporation by EPCs through clathrin-dependent endocytosis, phagocytosis, and caveolae-mediated uptake. The treatment of EPCs with basal, M1, and M2 macrophage culture media and EPC/macrophage coculture studies also confirmed the angiogenic effect of these nanospheres on EPCs, even in the presence of phagocytic cells. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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23 pages, 4527 KiB

Open AccessEditor’s ChoiceArticle

Synthesis of Polystyrene-Based Cationic Nanomaterials with Pro-Oxidant Cytotoxic Activity on Etoposide-Resistant Neuroblastoma Cells

by Silvana Alfei, Barbara Marengo, Giulia Elda Valenti and Cinzia Domenicotti

Nanomaterials 2021, 11(4), 977; https://doi.org/10.3390/nano11040977 - 10 Apr 2021

Cited by 17 | Viewed by 2017

Abstract

Drug resistance is a multifactorial phenomenon that limits the action of antibiotics and chemotherapeutics. Therefore, it is essential to develop new therapeutic strategies capable of inducing cytotoxic effects circumventing chemoresistance. In this regard, the employment of natural and synthetic cationic peptides and polymers [...] Read more.

Drug resistance is a multifactorial phenomenon that limits the action of antibiotics and chemotherapeutics. Therefore, it is essential to develop new therapeutic strategies capable of inducing cytotoxic effects circumventing chemoresistance. In this regard, the employment of natural and synthetic cationic peptides and polymers has given satisfactory results both in microbiology, as antibacterial agents, but also in the oncological field, resulting in effective treatment against several tumors, including neuroblastoma (NB). To this end, two polystyrene-based copolymers (P5, P7), containing primary ammonium groups, were herein synthetized and tested on etoposide-sensitive (HTLA-230) and etoposide-resistant (HTLA-ER) NB cells. Both copolymers were water-soluble and showed a positive surface charge due to nitrogen atoms, which resulted in protonation in the whole physiological pH range. Furthermore, P5 and P7 exhibited stability in solution, excellent buffer capacity, and nanosized particles, and they were able to reduce NB cell viability in a concentration-dependent way. Interestingly, a significant increase in reactive oxygen species (ROS) production was observed in both NB cell populations treated with P5 or P7, establishing for both copolymers an unequivocal correlation between cytotoxicity and ROS generation. Therefore, P5 and P7 could be promising template macromolecules for the development of new chemotherapeutic agents able to fight NB chemoresistance. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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21 pages, 7440 KiB

Open AccessArticle

Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells

by Karin Möller, Beth Macaulay and Thomas Bein

Nanomaterials 2021, 11(2), 489; https://doi.org/10.3390/nano11020489 - 15 Feb 2021

Cited by 17 | Viewed by 3342

Abstract

The efficiency of anti-cancer drugs is commonly determined by endpoint assays after extended incubation times, often after days. Here we demonstrate that curcumin encapsulated in crosslinked cyclodextrin nanoparticles (CD-NP) acts extremely rapidly on cell metabolism resulting in an immediate and complete inhibition of [...] Read more.

The efficiency of anti-cancer drugs is commonly determined by endpoint assays after extended incubation times, often after days. Here we demonstrate that curcumin encapsulated in crosslinked cyclodextrin nanoparticles (CD-NP) acts extremely rapidly on cell metabolism resulting in an immediate and complete inhibition of cell growth and in efficient cancer-cell killing only few hours after incubation. This early onset of anti-cancer action was discovered by live-cell high-throughput fluorescence microscopy using an environmental stage. To date, only very few examples of covalently crosslinked nanoscale CD-based (CD-NP) drug carriers exist. Crosslinking cyclodextrins enables the adsorption of unusually high payloads of hydrophobic curcumin (762 µg CC/mg CD-NP) reflecting a molar ratio of 2.3:1 curcumin to cyclodextrin. We have investigated the effect of CD-NP encapsulated curcumin (CD-CC-NP) in comparison to free, DMSO-derived curcumin nanoparticles (CC-NP) on 4 different cell lines. Very short incubations times as low as 1 h were applied and cell responses after medium change were subsequently followed over two days. We show that cell proliferation is inhibited nearly immediately in all cell lines and that a cell- and concentration dependent cancer-cell killing occurs. Anti-cancer effects were similar with free and encapsulated curcumin, however, encapsulation in CD-NP drastically extends the long-term photostability and anti-cancer activity of curcumin. Curcumin-sensitivity is highest in HeLa cells reaching up to 90% cell death under these conditions. Sensitivity decreased from HeLa to T24 to MDA MB-231 cells. Strikingly, the immortalized non-cancerous cell line MCF-10A was robust against curcumin concentrations that were highly toxic to the other cell lines. Our results underline the potential of curcumin as gentle and yet effective natural anti-cancer agent when delivered solvent-free in stabilizing and biocompatible drug carriers such as CD-NP that enable efficient cellular delivery. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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Review

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18 pages, 5819 KiB

Open AccessReview

Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

by Miguel Gisbert-Garzarán and María Vallet-Regí

Nanomaterials 2021, 11(9), 2222; https://doi.org/10.3390/nano11092222 - 28 Aug 2021

Cited by 21 | Viewed by 3360

Abstract

Mesoporous silica nanoparticles have been widely applied as carriers for cancer treatment. Among the different types of stimuli-responsive drug delivery systems, those sensitive to redox stimuli have attracted much attention. Their relevance arises from the high concentration of reductive species that are found [...] Read more.

Mesoporous silica nanoparticles have been widely applied as carriers for cancer treatment. Among the different types of stimuli-responsive drug delivery systems, those sensitive to redox stimuli have attracted much attention. Their relevance arises from the high concentration of reductive species that are found within the cells, compared to bloodstream, which leads to the drug release taking place only inside cells. This review is intended to provide a comprehensive overview of the most recent trends in the design of redox-responsive mesoporous silica nanoparticles. First, a general description of the biological rationale of this stimulus is presented. Then, the different types of gatekeepers that are able to open the pore entrances only upon application of reductive conditions will be introduced. In this sense, we will distinguish among those targeted and those non-targeted toward cancer cells. Finally, a new family of bridged silica nanoparticles able to degrade their structure upon application of this type of stimulus will be presented. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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20 pages, 1551 KiB

Open AccessReview

Nanoparticles for the Treatment of Inner Ear Infections

by Dan Cristian Gheorghe, Adelina-Gabriela Niculescu, Alexandra Cătălina Bîrcă and Alexandru Mihai Grumezescu

Nanomaterials 2021, 11(5), 1311; https://doi.org/10.3390/nano11051311 - 17 May 2021

Cited by 17 | Viewed by 5458

Abstract

The inner ear is sensitive to various infections of viral, bacterial, or fungal origin, which, if left untreated, may lead to hearing loss or progress through the temporal bone and cause intracranial infectious complications. Due to its isolated location, the inner ear is [...] Read more.

The inner ear is sensitive to various infections of viral, bacterial, or fungal origin, which, if left untreated, may lead to hearing loss or progress through the temporal bone and cause intracranial infectious complications. Due to its isolated location, the inner ear is difficult to treat, imposing an acute need for improving current therapeutic approaches. A solution for enhancing antimicrobial treatment performance is the use of nanoparticles. Different inorganic, lipidic, and polymeric-based such particles have been designed, tested, and proven successful in the controlled delivery of medication, improving drug internalization by the targeted cells while reducing the systemic side effects. This paper makes a general presentation of common inner ear infections and therapeutics administration routes, further focusing on newly developed nanoparticle-mediated treatments. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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26 pages, 2121 KiB

Open AccessReview

Inorganic and Polymeric Nanoparticles for Human Viral and Bacterial Infections Prevention and Treatment

by John Jairo Aguilera-Correa, Jaime Esteban and María Vallet-Regí

Nanomaterials 2021, 11(1), 137; https://doi.org/10.3390/nano11010137 - 08 Jan 2021

Cited by 27 | Viewed by 5442

Abstract

Infectious diseases hold third place in the top 10 causes of death worldwide and were responsible for more than 6.7 million deaths in 2016. Nanomedicine is a multidisciplinary field which is based on the application of nanotechnology for medical purposes and can be [...] Read more.

Infectious diseases hold third place in the top 10 causes of death worldwide and were responsible for more than 6.7 million deaths in 2016. Nanomedicine is a multidisciplinary field which is based on the application of nanotechnology for medical purposes and can be defined as the use of nanomaterials for diagnosis, monitoring, control, prevention, and treatment of diseases, including infectious diseases. One of the most used nanomaterials in nanomedicine are nanoparticles, particles with a nano-scale size that show highly tunable physical and optical properties, and the capacity to a wide library of compounds. This manuscript is intended to be a comprehensive review of the available recent literature on nanoparticles used for the prevention and treatment of human infectious diseases caused by different viruses, and bacteria from a clinical point of view by basing on original articles which talk about what has been made to date and excluding commercial products, but also by highlighting what has not been still made and some clinical concepts that must be considered for futures nanoparticles-based technologies applications. Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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Other

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28 pages, 4591 KiB

Open AccessSystematic Review

Electromagnetically Stimuli-Responsive Nanoparticles-Based Systems for Biomedical Applications: Recent Advances and Future Perspectives

by Raffaele Longo, Giuliana Gorrasi and Liberata Guadagno

Nanomaterials 2021, 11(4), 848; https://doi.org/10.3390/nano11040848 - 26 Mar 2021

Cited by 27 | Viewed by 2758

Abstract

Nanoparticles (NPs) in the biomedical field are known for many decades as carriers for drugs that are used to overcome biological barriers and reduce drug doses to be administrated. Some types of NPs can interact with external stimuli, such as electromagnetic radiations, promoting [...] Read more.

Nanoparticles (NPs) in the biomedical field are known for many decades as carriers for drugs that are used to overcome biological barriers and reduce drug doses to be administrated. Some types of NPs can interact with external stimuli, such as electromagnetic radiations, promoting interesting effects (e.g., hyperthermia) or even modifying the interactions between electromagnetic field and the biological system (e.g., electroporation). For these reasons, at present these nanomaterial applications are intensively studied, especially for drugs that manifest relevant side effects, for which it is necessary to find alternatives in order to reduce the effective dose. In this review, the main electromagnetic-induced effects are deeply analyzed, with a particular focus on the activation of hyperthermia and electroporation phenomena, showing the enhanced biological performance resulting from an engineered/tailored design of the nanoparticle characteristics. Moreover, the possibility of integrating these nanofillers in polymeric matrices (e.g., electrospun membranes) is described and discussed in light of promising applications resulting from new transdermal drug delivery systems with controllable morphology and release kinetics controlled by a suitable stimulation of the interacting systems (nanofiller and interacting cells). Full article

(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)

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