Prussian Blue Nanoparticles and Their Analogues for Application to Cancer Theranostics
2016; Future Medicine; Volume: 11; Issue: 6 Linguagem: Inglês
10.2217/nnm.16.16
ISSN1748-6963
Autores Tópico(s)Nanocluster Synthesis and Applications
ResumoNanomedicineVol. 11, No. 6 EditorialFree AccessPrussian blue nanoparticles and their analogues for application to cancer theranosticsChitta Ranjan PatraChitta Ranjan Patra*Author for correspondence: E-mail Address: crpatra@iict.res.in Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana, India Academy of Scientific & Innovative Research (AcSIR), Taramani, Chennai- 600113, IndiaPublished Online:25 Feb 2016https://doi.org/10.2217/nnm.16.16AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: biocompatiblecancer theranosticsdrug deliverynanomedicinePrussian blue nanoparticlesUS FDA-approved drugFirst draft submitted: 15 December 2015; Accepted for publication: 22 January 2016; Published online: 25 February 2016Prussian blue nanoparticles: background & applicationsPrussian blue (PB), a mixed valance hexacyanomatelate salt, was historically known as ancient dark blue pigment. The discovery and 290 years of history of PB has been well documented by Kraft and Berlin [1]. PB (ferric hexacyanoferrate) and its analogues are well known inorganic salts of co-ordination complexes that show interesting electro, photochemical, biochemical and magnetic properties [2]. The porous nature and special unique properties of PB make them suitable candidates for several biological, medicinal and other applications including photonics, magneto-optical devices, catalysis, energy storage, staining agent for histology study, chelating agent for the removal of heavy metals and radioactive elements [3–5]. Among all applications, Prussian blue nanoparticles (PBNPs) have been extensively used for several biomedical applications including drug delivery due to several advantages like their biocompatible nature, biodegradability, ease to synthesize, controllable shape and morphology, and low production cost. Additionally, Prussian blue capsule, also known as Radiogardase (an active pharmaceutical ingredient), has been approved by the US FDA in 2003 as a safe oral antidote and effective for the treatment of internal contamination with radioactive and nonradioactive metals (thallium, cesium). It works by the combination of thallium and cesium in the intestine and the combined complex is removed from the body through stool.Theranostic applications of Prussian blue nanoparticles & their analoguesOver the past 10 years, nanomedicine has become an emerging field of nanotechnology applications to health. Recently, several groups including ours have investigated the development of metal nanoparticle-based theranostic approaches for the treatment of several diseases including cancer, antibacterial activity and cardiovascular related diseases [5–11]. Hence, design, development, fabrication metal nanoparticles or inorganic complex nanoparticles, especially PBNPs, through a simple, efficient and economically cheap method is a very important area for nanobiotechnology research because of its medicinal applications [9,12–14]. In this context, we demonstrated a simple, efficient, fast, template free, cost-effective and eco-friendly method for the synthesis of copper analogues of Prussian blue (Cu-PBNPs) nanoparticles that are stable and biocompatible, observed by several analytical techniques and in vitro assays. The Cu-PBNPs was synthesized by the interaction of CuSO4 solution and K3Fe(CN)6 at room temperature with different volume ratio. The PBNPs with 1:1 molar ratio of CuSO4 and K3Fe(CN)6 is considered as optimized PBNPs based on the stability, biocompatibility and release kinetics of the drug release. These nanoparticles successfully deliver the doxorubicin drug to cancer cells. Additionally, these nanoparticles exhibit the selective quenching of fluorescence of doxorubicin compared with PB analogues with other metals ions. Considering its multifunctional biological activities including sustained and slow release of anticancer drug (doxorubicin: DOX), delivery of DOX to the cancer cells, nuclear targeting property and selective fluorescence quenching property to metal ions, these nanoparticles could be useful for potential theranostics applications in biomedical sciences [5].Since pediatric brain tumor (PBT) is a primary cause of death in children, the development of molecularly-specific imaging agents is urgently needed to monitor disease progression and therapeutic treatment. Dumont et al., demonstrated the manganese-containing Prussian blue nanoparticles (Mn-PBNPs) (where Mn2+ ions are used for paramagnetic property) as molecular MRI and fluorescence-based imaging agent for the diagnostic treatment of PBT [15]. The functionalization of manganese-containing nanoparticles consists of fluorescent avidin that works for dual action (enabling fluorescence imaging help in the attachment for biotinylated ligands that target PBT) based on the orthotopic mouse model of PBTs. Jing et al. demonstrated the photoabsorbing agent of core/shell nanoparticles of gold and Prussian blue (Au@PBNPs) for photothermal therapy and photoacoustic (PA) imaging because of high molar extinction coefficient in near- infrared (NIR) region and high photostability [16]. These nanoparticles could be used as an effective cancer diagnostic with noninvasive therapy for cancer therapy in future. Wang et al. demonstrated that PBNPs could be useful for the delivery of DNA drugs towards cancer cells after surface functionalization with 11–mercaptoundecanoic acid (MUA) and conjugation of drug, decoy oligodeoxynucleotide (dODN) [17]. The drug delivery system (dODN@MUA-PBNPs) was internalized inside the cytoplasmic compartment of the cells after endocytosis and able to kill cancer cells. Noroozifar et al. reported the synthesis of silver hexacyanoferrate nanoparticles that could be useful for the simultaneous determination of ascorbic acid, dopamine and uric acid present in biological fluid (urine and human blood serum) samples with good sensitivity and selectivity [18]. Dumont et al. reported the synthesis, characterization, stability, cytotoxicity, fluorescence and MR imaging capabilities of the biofunctionalized Prussian blue NPs that could be used as multimodal molecular imaging agents in near future [19]. Another study reported by Fu et al. demonstrated the fabrication of a new core shell theranostic agent (Fe3O4@PB NPs) by the combination of two FDA approved materials (PBNPs and superparamagnetic Fe3O4 NP). Here PBNPs are used as NIR-driven photothermal agent for photothermal therapy treatment of cancer due to its strong optical absorbance in NIR region and high photothermal conversion efficiency and has been used as the contrast enhancement agent for MRI. The newly designed nanoshell will have great potential as a new theranostic nanomedicine for clinical applications [13]. Fiorito et al. demonstrated the synthesis of PBNPs using FeCl3 and K3Fe(CN)6 and showed the immobilized NPs in multilayer structure for the development of potential amperometric transducer for oxidase-enzyme-based biosensors. The technique could be useful as a potential tool for a biosensing device [12]. Lian et al. designed single crystalline highly biocompatible coordination polymer PBNPs and successfully delivered the cis-plation to the bladder cancer cells (T24 cells). The PBNPs are nontoxic because cyanide groups are tightly bound to the Fe atom. The authors claim hollow PBNPs could be useful as an efficient drug delivery in cancer therapy [14]. Biocompatible Prussian blue nanoparticles that can penetrate the cell membrane have also been investigated for dual action including as an MRI agent as well as for a therapeutic purpose due to the presence of super paramagnetic iron oxides (imaging as well as drug delivery vehicle) [7]. Stable and narrow-sized (around 4 nm) PBNPs protected by polyvinylpyrrolidone have been utilized as a sensitive label-free immunodetection (detection limit from 200 μg ml-1 to 34 pg human IgG ml-1) for a cancer (parathyroid hormone-related protein, PTHrP), observed by in vitro experiments [6]. Jing et al. demonstrated the fabrication of a multifunctional nanoagent system after modification of hollow Prussian blue nanoparticles (HPBNPs: as photothermal agent and drug carrier), using hyaluronic acid grafting polyethylene glycol (HA-g-PEG: capping agent to increase the colloidal stability, prolonged blood circulation time, targeting ability because of cancer targeting HA to the surface of HeLa cells over-expressing the CD44 receptor) and 10-hydroxycamptothecin (as chemotherapeutic agent) for tumor-targeted thermochemotherapy. The synergetic effect (combination of both photothermal therapy and chemotherapy) of multifunctional HPBNPs in both in vitro and in vivo systems shows enhanced therapeutic efficacy compared with either photothermal therapy or chemotherapy alone. Therefore, the multifunctional HPBNPs could be useful as promising theranostic nanomedicine (noninvasive imaging and remote-controlled therapy) in the near future [9]. Li et al. reported the development of a strategy for sensitive electrochemical immunoassay of human tissue polypeptide antigen, cancer marker using Prussian blue nanoparticles-doped nanogold microsphere (AuPB) as promoter [20]. The electrochemical immunoassay shows nice electrochemical responses for the detection of tissue polypeptide antigen at low concentration range (5 pg ml-1). The authors validated the data for the analysis of eight clinic human serum specimens and eight spiked serum samples and the results corroborate with the referenced enzyme-linked immunosorbent assay (ELISA) method.Potential long-term toxicity issues & future perspectiveExtensive safety assessment of any nanoparticles for investigating toxicity must be evaluated in a preclinical model to satisfy regulators as well as patients before administration in the human body or clinical trial. Hence, efficacy, biosafety, metabolic long-term fate (in vitro and in vivo), pharmacokinetics profiles, potential long-term toxicity study of PBNPs in a mouse model should be systematically evaluated before using these novel materials in a clinical trial [11]. Several reports support the biocompatible nature and nontoxicity of PBNPs, both in in vitro and in vivo systems, may be due to cyano groups being tightly bound to the iron metal in PBNPs. It was reported that the citrate-coated PBNPs exhibited no significant cytotoxicity [7]. The nontoxic Prussian blue has been extensively used as a pigment in industry and for artists since 1704. Nowadays, PB is used in several applications including catalysis, energy storage, chelating agent and medicinal and biological applications. Recently, Prussian blue capsule (Radiogardase) has been approved by FDA as an oral antidote for the elimination of radioactive and nonradioactive cesium and thallium poisoning metal ions from human body. Since PBNP is a nontoxic and FDA-approved compound and already used clinically as an antidote for the elimination of radioactive and nonradioactive thallium and cesium poisoning metal ions from the human body, therefore we strongly believe that Prussian blue nanoparticles and their analogues could be useful for potential cancer theranostics in the near future.Financial & competing interests disclosureThis research was supported by the 'Ramanujan Fellowship grant' (SR/S2/RJN–04/2010; GAP0305), DST-New Delhi and 'CSIR 12th Five Year Plan (FYP) project (ADD: CSC0302) to CR Patra. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.References1 Kraft A, Berlin GG. On the discovery and history of prussian blue. Bull. Hist. 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LtdKeywordsbiocompatiblecancer theranosticsdrug deliverynanomedicinePrussian blue nanoparticlesUS FDA-approved drugFinancial & competing interests disclosureThis research was supported by the 'Ramanujan Fellowship grant' (SR/S2/RJN–04/2010; GAP0305), DST-New Delhi and 'CSIR 12th Five Year Plan (FYP) project (ADD: CSC0302) to CR Patra. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download
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