Special Issue "Nanoparticles in Theranostics"

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (31 August 2015)

Special Issue Editors

Guest Editor
Dr. Subramanian Tamil Selvan

Institute of Materials Research and Engineering (IMRE), 3 Research Link, 117602, Singapore
Website | E-Mail
Fax: +65 6774 4657
Interests: nanoparticles; quantum dots; synthesis; surface functionalization; optical and magnetic properties; multifunctional nanoparticles; bioimaging; drug delivery; nanomedicine; biomaterials; Tissue Engineering; Personal Care; polymer composites; solar cells
Guest Editor
Prof. Dr. Wolfgang J. Parak

Fachbereich Physik, Philipps Universität Marburg, Renthof 7, 35037 Marburg, Germany
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Fax: +49 6421 2827 034
Interests: nanoparticles; colloids and surfaces; surface functionalisation; synthesis methods; spectroscopy; cellular uptake; imaging; sensing; drug delivery; nanomedicine
Guest Editor
Dr. Pablo del Pino

Laboratory of Biofunctional Nanomaterials, CIC biomaGUNE, Paseo Miramon 182, 20009 Donostia-San Sebastian, Spain
Website | E-Mail
Fax: +34 943 00 53 01

Special Issue Information

Dear Colleagues,

Theranostics is a new term which combines therapy and diagnostics. Theranostic nanomedicine is an emerging paradigm, involving the use of nanoparticles or other nanomaterials for diagnostics, imaging, and therapeutic applications. In recent years, much research efforts have been devoted toward the goal of developing different nanoplatforms for theranostic nanomedicine applications. Both polymeric and inorganic nanoparticles have been thoroughly enjoying their uses in the area of biological imaging and therapy.

This Special Issue focuses on the use of emerging polymeric nanoparticles and inorganic nanoparticles (quantum dots, magnetic, upconversion and other graphene nanoparticles) in theranostics applications.

Prof. Dr. Subramanian Tamil Selvan
Prof. Dr. Wolfgang J. Parak
Dr. Pablo del Pino
Guest Editors

Manuscript Submission Information

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Keywords

  • nanoparticles
  • quantum dots
  • upconversion nanoparticles
  • magnetic nanoparticles
  • polymeric nanoparticles
  • imaging
  • therapy
  • theranostics

Published Papers (12 papers)

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Research

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Open AccessArticle Mesoporous Silica Nanoparticles Loaded with Cisplatin and Phthalocyanine for Combination Chemotherapy and Photodynamic Therapy in vitro
Nanomaterials 2015, 5(4), 2302-2316; doi:10.3390/nano5042302
Received: 7 October 2015 / Revised: 3 December 2015 / Accepted: 10 December 2015 / Published: 16 December 2015
Cited by 12 | PDF Full-text (1862 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and
[...] Read more.
Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and cytotoxicity were evaluated in human cervical cancer (HeLa) cells by confocal laser scanning microscopy (CLSM) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. The CLSM experiments showed that the MSN materials can be readily internalized in HeLa cells. The cytotoxic experiments demonstrated that, after light exposure, the combination of both AlClPc and cisplatin compounds in the same MSN platform potentiate the toxic effect against HeLa cells in comparison to the control AlClPc-MSN and cisplatin-MSN materials. These results show the potential of using MSN platforms as nanocarriers for combination photodynamic and chemotherapies to treat cancer. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Iron Oxide Nanoparticles Coated with a Phosphorothioate Oligonucleotide and a Cationic Peptide: Exploring Four Different Ways of Surface Functionalization
Nanomaterials 2015, 5(4), 1588-1609; doi:10.3390/nano5041588
Received: 18 August 2015 / Revised: 22 September 2015 / Accepted: 23 September 2015 / Published: 29 September 2015
Cited by 3 | PDF Full-text (996 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The superparamagnetic iron oxide nanoparticles (SPIONs) have great potential in therapeutic and diagnostic applications. Due to their superparamagnetic behavior, they are used clinically as a Magnetic Resonance Imaging (MRI) contrast agent. Iron oxide nanoparticles are also recognized todays as smart drug-delivery systems. However,
[...] Read more.
The superparamagnetic iron oxide nanoparticles (SPIONs) have great potential in therapeutic and diagnostic applications. Due to their superparamagnetic behavior, they are used clinically as a Magnetic Resonance Imaging (MRI) contrast agent. Iron oxide nanoparticles are also recognized todays as smart drug-delivery systems. However, to increase their specificity, it is essential to functionalize them with a molecule that effectively targets a specific area of the body. Among the molecules that can fulfill this role, peptides are excellent candidates. Oligonucleotides are recognized as potential drugs for various diseases but suffer from poor uptake and intracellular degradation. In this work, we explore four different strategies, based on the electrostatic interactions between the different partners, to functionalize the surface of SPIONs with a phosphorothioate oligonucleotide (ODN) and a cationic peptide labeled with a fluorophore. The internalization of the nanoparticles has been evaluated in vitro on RAW 264.7 cells. Among these strategies, the “«one-step assembly»”, i.e., the direct complexation of oligonucleotides and peptides on iron oxide nanoparticles, provides the best way of coating for the internalization of the nanocomplexes. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Surface Wettability Modification of Cyclic Olefin Polymer by Direct Femtosecond Laser Irradiation
Nanomaterials 2015, 5(3), 1442-1453; doi:10.3390/nano5031442
Received: 16 July 2015 / Revised: 21 August 2015 / Accepted: 24 August 2015 / Published: 28 August 2015
Cited by 7 | PDF Full-text (1819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The effect of laser irradiation on surface wettability of cyclic olefin polymer (COP) was investigated. Under different laser parameters, a superhydrophilic or a superhydrophobic COP surface with a water contact angle (WCA) of almost 0° or 163°, respectively, could be achieved by direct
[...] Read more.
The effect of laser irradiation on surface wettability of cyclic olefin polymer (COP) was investigated. Under different laser parameters, a superhydrophilic or a superhydrophobic COP surface with a water contact angle (WCA) of almost 0° or 163°, respectively, could be achieved by direct femtosecond laser irradiation. The laser power deposition rate (PDR) was found to be a key factor on the wettability of the laser-treated COP surface. The surface roughness and surface chemistry of the laser-irradiated samples were characterized by surface profilometer and X-ray photoelectron spectroscopy, respectively; they were found to be responsible for the changes of the laser-induced surface wettability. The mechanisms involved in the laser surface wettability modification process were discussed. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Comparison of the in Vitro Uptake and Toxicity of Collagen- and Synthetic Polymer-Coated Gold Nanoparticles
Nanomaterials 2015, 5(3), 1418-1430; doi:10.3390/nano5031418
Received: 3 August 2015 / Revised: 19 August 2015 / Accepted: 20 August 2015 / Published: 27 August 2015
Cited by 8 | PDF Full-text (982 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We studied the physico-chemical properties (size, shape, zeta-potential), cellular internalization and toxicity of gold nanoparticles (NPs) stabilized with the most abundant mammalian protein, collagen. The properties of these gold NPs were compared to the same sized gold NPs coated with synthetic poly(isobutylene-alt-maleic anhydride)
[...] Read more.
We studied the physico-chemical properties (size, shape, zeta-potential), cellular internalization and toxicity of gold nanoparticles (NPs) stabilized with the most abundant mammalian protein, collagen. The properties of these gold NPs were compared to the same sized gold NPs coated with synthetic poly(isobutylene-alt-maleic anhydride) (PMA). Intracellular uptake and cytotoxicity were assessed in two cell lines (cervical carcinoma and lung adenocarcinoma cells) by employing inductively-coupled plasma-mass spectrometry (ICP-MS) analysis and a cell viability assay based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. We found that the collagen-coated gold NPs exhibit lower cytotoxicity, but higher uptake levels than PMA-coated gold NPs. These results demonstrate that the surface coating of Au NPs plays a decisive role in their biocompatibility. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Hyaluronic Acid-Chitosan Nanoparticles to Deliver Gd-DTPA for MR Cancer Imaging
Nanomaterials 2015, 5(3), 1379-1396; doi:10.3390/nano5031379
Received: 1 June 2015 / Revised: 28 July 2015 / Accepted: 13 August 2015 / Published: 20 August 2015
Cited by 6 | PDF Full-text (3184 KB) | HTML Full-text | XML Full-text
Abstract
Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially at the early stage of tumors. Recently, polyionic nanocomplexes (PICs), which are composed of polyanions and opposite polycations, have been demonstrated to be a promising strategy for biomedical applications.
[...] Read more.
Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially at the early stage of tumors. Recently, polyionic nanocomplexes (PICs), which are composed of polyanions and opposite polycations, have been demonstrated to be a promising strategy for biomedical applications. In this work, chitosan-hyaluronic acid nanoparticles (GCHN) were developed to deliver Gd-DTPA as MRI contrast agents for tumor diagnosis. The Gd-labeled conjugates (CS-DTPA-Gd) were successfully synthesized by carbodiimide reaction, and then GCHN were prepared by ionic gelation using the obtained CS-DTPA-Gd and hyaluronic acid. The morphology of GCHN was spherical or ellipsoidal, which is observed by transmission electronic microscopy (TEM). The mean particle size and zeta potential of GCHN were 213.8 ± 2.6 nm and 19.92 ± 1.69 mV, respectively. The significant enhancement of signal intensity induced by GCHN was observed both in vitro and in vivo. Also, compared with Magnevist, GCHN was witnessed for a prolonged imaging time in the B16 tumor-bearing mice model. Furthermore, GCHN were verified as below toxic both in vitro and in vivo. These results indicated that GCHN could potentially be an alternative to current MRI contrast agents for tumor diagnosis. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Conjugation of Polymer-Coated Gold Nanoparticles with Antibodies—Synthesis and Characterization
Nanomaterials 2015, 5(3), 1297-1316; doi:10.3390/nano5031297
Received: 28 June 2015 / Revised: 27 July 2015 / Accepted: 30 July 2015 / Published: 7 August 2015
Cited by 6 | PDF Full-text (3036 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of polymer-coated gold nanoparticles with high colloidal stability is described, together with appropriate characterization techniques concerning the colloidal properties of the nanoparticles. Antibodies against vascular endothelial growth factor (VEGF) are conjugated to the surface of the nanoparticles. Antibody attachment is probed
[...] Read more.
The synthesis of polymer-coated gold nanoparticles with high colloidal stability is described, together with appropriate characterization techniques concerning the colloidal properties of the nanoparticles. Antibodies against vascular endothelial growth factor (VEGF) are conjugated to the surface of the nanoparticles. Antibody attachment is probed by different techniques, giving a guideline about the characterization of such conjugates. The effect of the nanoparticles on human adenocarcinoma alveolar basal epithelial cells (A549) and human umbilical vein endothelial cells (HUVECs) is probed in terms of internalization and viability assays. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption
Nanomaterials 2015, 5(3), 1284-1296; doi:10.3390/nano5031284
Received: 25 June 2015 / Revised: 23 July 2015 / Accepted: 24 July 2015 / Published: 31 July 2015
Cited by 2 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak
[...] Read more.
Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessCommunication Targeting of Apoptotic Cells Using Functionalized Fe2O3 Nanoparticles
Nanomaterials 2015, 5(2), 874-884; doi:10.3390/nano5020874
Received: 29 March 2015 / Accepted: 20 May 2015 / Published: 26 May 2015
Cited by 1 | PDF Full-text (2891 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fe2O3 nanoparticles (NPs) have been synthesized and functionalized with SiO2 and -NH2 group, respectively. Conjugation to fluorescently-labeled poly-caspase inhibitor (SR-FLIVO) has been carried out for better cellular uptake studies of apoptosis arising from brain focal cerebral ischemia. Highest
[...] Read more.
Fe2O3 nanoparticles (NPs) have been synthesized and functionalized with SiO2 and -NH2 group, respectively. Conjugation to fluorescently-labeled poly-caspase inhibitor (SR-FLIVO) has been carried out for better cellular uptake studies of apoptosis arising from brain focal cerebral ischemia. Highest conjugation affinity to SR-FLIVO was found to be ca. 80% for Fe2O3-SiO-NH2 functionalized nanoparticles (FNPs). Tracking of SR-FLIVO conjugated functionalized nanoparticles (SR-FLIVO-FNPs) in vivo and in vitro has been carried out and detected using microscopic techniques after histochemical staining methods. Experimental results revealed that SR-FLIVO-FNPs probe could passively cross the blood brain barrier (BBB) and accumulated within the apoptotic cell. Optimization of SR-FLIVO-FNPs probe can effectively promise to open a new era for intracellular drug delivery and brain diagnosis. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessArticle Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment
Nanomaterials 2015, 5(1), 298-320; doi:10.3390/nano5010298
Received: 9 January 2015 / Revised: 9 February 2015 / Accepted: 27 February 2015 / Published: 5 March 2015
Cited by 3 | PDF Full-text (5150 KB) | HTML Full-text | XML Full-text
Abstract
Chemokines (CKs) secreted by the host cells into surrounding tissue establish concentration gradients directing the migration of leukocytes. We propose an in vivo CK gradient remodeling approach based on sustained release of CKs by the crosslinked poly(N-isopropylacrylamide) hydrogel open meshwork nano-particles (NPs) containing
[...] Read more.
Chemokines (CKs) secreted by the host cells into surrounding tissue establish concentration gradients directing the migration of leukocytes. We propose an in vivo CK gradient remodeling approach based on sustained release of CKs by the crosslinked poly(N-isopropylacrylamide) hydrogel open meshwork nano-particles (NPs) containing internal crosslinked dye affinity baits for a reversible CK binding and release. The sustained release is based on a new principle of affinity off-rate tuning. The NPs with Cibacron Blue F3G-A and Reactive Blue-4 baits demonstrated a low-micromolar affinity binding to IL-8, MIP-2, and MCP-1 with a half-life of several hours at 37 °C. The capacity of NPs loaded with IL-8 and MIP-1α to increase neutrophil recruitment to lymph nodes (LNs) was tested in mice after footpad injection. Fluorescently-labeled NPs used as tracers indicated the delivery into the sub-capsular compartment of draining LNs. The animals administered the CK-loaded NPs demonstrated a widening of the sub-capsular space and a strong LN influx of leukocytes, while mice injected with control NPs without CKs or bolus doses of soluble CKs alone showed only a marginal neutrophil response. This technology provides a new means to therapeutically direct or restore immune cell traffic, and can also be employed for simultaneous therapy delivery. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Review

Jump to: Research

Open AccessReview Receptor-Mediated Drug Delivery Systems Targeting to Glioma
Nanomaterials 2016, 6(1), 3; doi:10.3390/nano6010003
Received: 25 September 2015 / Revised: 8 November 2015 / Accepted: 24 November 2015 / Published: 28 December 2015
Cited by 4 | PDF Full-text (889 KB) | HTML Full-text | XML Full-text
Abstract
Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment
[...] Read more.
Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessReview Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge
Nanomaterials 2015, 5(4), 2231-2248; doi:10.3390/nano5042231
Received: 29 October 2015 / Revised: 25 November 2015 / Accepted: 8 December 2015 / Published: 11 December 2015
Cited by 6 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the
[...] Read more.
The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the different approaches employed to overcome this barrier, the use of nanoparticles as a tool to enhance delivery of therapeutic molecules to the brain is particularly promising. There is special interest in the use of magnetic nanoparticles, as their physical characteristics endow them with additional potentially useful properties. Following systemic administration, a magnetic field applied externally can mediate the capacity of magnetic nanoparticles to permeate the blood-brain barrier. Meanwhile, thermal energy released by magnetic nanoparticles under the influence of radiofrequency radiation can modulate blood-brain barrier integrity, increasing its permeability. In this review, we present the strategies that use magnetic nanoparticles, specifically iron oxide nanoparticles, to enhance drug delivery to the brain. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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Open AccessReview Gold Nanotheranostics: Proof-of-Concept or Clinical Tool?
Nanomaterials 2015, 5(4), 1853-1879; doi:10.3390/nano5041853
Received: 22 August 2015 / Revised: 4 October 2015 / Accepted: 27 October 2015 / Published: 3 November 2015
Cited by 18 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text
Abstract
Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial—nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting,
[...] Read more.
Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial—nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact. Full article
(This article belongs to the Special Issue Nanoparticles in Theranostics)
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