Special Issue "Nanotheranostics and Cancer: Where Are We Now?"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (15 November 2018).

Special Issue Editors

Prof. Dr. Alberto Pais
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Guest Editor
Coimbra Chemistry Centre, CQC, Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Rua Larga, 3004-535 Portugal
Interests: nanoparticles; nucleic acids; pharmaceutical technology; supramolecular chemistry; molecular simulation; chemometrics and data science
Special Issues and Collections in MDPI journals
Dr. Carla Vitorino
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Co-Guest Editor
Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
Coimbra Chemistry Center, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
Centre for Neurosciences and Cell Biology (CNC), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
Interests: nanotechnology; transdermal/topical systems; skin delivery; lipid nanoparticles; controlled release; brain drug delivery; cancer therapy; quality by design
Special Issues and Collections in MDPI journals
Dr. João Sousa
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Co-Guest Editor
Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
Coimbra Chemistry Center, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
Interests: oral sustained release formulations; skin delivery; nanotechnology; aseptic technology; regulatory affairs
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Nanotheranostics promise to provide innovative and more effective approaches for early diagnosis, imaging and therapy. Indeed, the design of nanoparticles to serve therapeutic and diagnostic purposes has dramatically increased, especially for the treatment of cancer. Note that an effective treatment requires improved diagnostic and therapeutic techniques with minimal side-effects. This dual approach enables to understand the location of tumor tissue, the biodistribution of nanoparticles, the progress and efficacy of the treatment, being highly useful for personalized medicine-based therapeutic interventions. In order to expand the theranostic approaches, different active strategies could be used to modulate the surface of nanotheranostic particles, including surface markers, proteins, drugs or genes, also taking advantage of the microenvironment characteristics using stimuli responsive triggers. The development of new nanotheranostic approaches represents an important step forward in the field of drug delivery systems.

This Special Issue has the aim of highlighting current progress in the use of the nanotheranostics in cancer treatment.

Dr. Alberto Canelas Pais
Dr. Carla Vitorino
Dr. João Sousa
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanotheranostics
  • Cancer
  • Functionalization
  • Active targeting
  • Nanomedicine
  • Nanoscience
  • Drug delivery
  • Gene delivery
  • Imaging

Published Papers (12 papers)

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Research

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Open AccessArticle
Magnetic Mixed Micelles Composed of a Non-Ionic Surfactant and Nitroxide Radicals Containing a d-Glucosamine Unit: Preparation, Stability, and Biomedical Application
Pharmaceutics 2019, 11(1), 42; https://doi.org/10.3390/pharmaceutics11010042 - 19 Jan 2019
Cited by 2
Abstract
Metal-free magnetic mixed micelles (mean diameter: < 20 nm) were prepared by mixing the biocompatible non-ionic surfactant Tween 80 and the non-toxic, hydrophobic pyrrolidine-N-oxyl radicals bearing a d-glucosamine unit in pH 7.4 phosphate-buffered saline (PBS). The time-course stability and in [...] Read more.
Metal-free magnetic mixed micelles (mean diameter: < 20 nm) were prepared by mixing the biocompatible non-ionic surfactant Tween 80 and the non-toxic, hydrophobic pyrrolidine-N-oxyl radicals bearing a d-glucosamine unit in pH 7.4 phosphate-buffered saline (PBS). The time-course stability and in vitro magnetic resonance imaging (MRI) contrast ability of the mixed micelles was found to depend on the length of the alkyl chain in the nitroxide radicals. It was also confirmed that the mixed micelles exhibited no toxicity in vivo and in vitro and high stability in the presence of a large excess of ascorbic acid. The in vivo MRI experiment revealed that one of these mixed micelles showed much higher contrast enhancement in the proton longitudinal relaxation time (T1) weighted images than other magnetic mixed micelles that we have reported previously. Thus, the magnetic mixed micelles presented here are expected to serve as a promising contrast agent for theranostic nanomedicines, such as MRI-visible targeted drug delivery carriers. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessArticle
HSA—Coated Magnetic Nanoparticles for MRI-Guided Photodynamic Cancer Therapy
Pharmaceutics 2018, 10(4), 284; https://doi.org/10.3390/pharmaceutics10040284 - 17 Dec 2018
Cited by 4
Abstract
Background: Photodynamic therapy (PDT) is a promising technique for cancer treatment; however, low tissue permeability for irradiating light and insufficient photosensitizer (PS) accumulation in tumors limit its clinical potential. Nanoparticles are engineered to improve selective drug delivery to tumor sites, but its accumulation [...] Read more.
Background: Photodynamic therapy (PDT) is a promising technique for cancer treatment; however, low tissue permeability for irradiating light and insufficient photosensitizer (PS) accumulation in tumors limit its clinical potential. Nanoparticles are engineered to improve selective drug delivery to tumor sites, but its accumulation is highly variable between tumors and patients. Identifying PS accumulation peak in a personalized manner is crucial for therapeutic outcome. Magnetic nanoparticles (MNPs) provide opportunity for tracking drug accumulation in dynamics using non-invasive magnetic resonance imaging (MRI). The purpose of the study was to evaluate MNP loaded with PS as a theranostic tool for treating cancer in mice xenograft colon cancer models. Methods: MNPs coated with human serum albumin (HSA) were loaded with bacteriochlorine a. MRI, atomic emission spectroscopy (AES) and fluorescent imaging were used to study MNP and drug accumulation rates and dynamics in CT26 tumors. Tumor growth curves were evaluated in animals that received PDT at different time points upon MNP systemic injection. Results: Peak MNP accumulation in tumors was detected by MRI 60 min post injection (pi) and the data were verified by AES and fluorescent imaging. Up to 17% of injected dose/g of tissue was delivered to malignant tissues 24 h after injection. Consistent with MRI predicted drug accumulation peak PDT performed 60 min after intravenous injection was more efficient in inhibiting tumor growth than treatment scheduled 30 min and 240 min pi. Conclusions: PS loading on HAS-coated MNPs is a perspective approach to increase drug delivery to tumor site. Tracking for MNP accumulation by MRI can be used to predict drug concentration peak in tumors and to adjust PDT time scheduling for improved antitumor response. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessCommunication
Anionic Long-Circulating Quantum Dots for Long-Term Intravital Vascular Imaging
Pharmaceutics 2018, 10(4), 244; https://doi.org/10.3390/pharmaceutics10040244 - 20 Nov 2018
Cited by 6
Abstract
A major impediment to the long-term in vivo vascular imaging is a lack of suitable probes and contrast agents. Our developed mercaptosuccinic acid (MSA) capped cadmium telluride/cadmium sulfide (CdTe/CdS) ultrasmall quantum dots (QDs) have high fluorescent quantum yield, long fluorescence lifetime and long [...] Read more.
A major impediment to the long-term in vivo vascular imaging is a lack of suitable probes and contrast agents. Our developed mercaptosuccinic acid (MSA) capped cadmium telluride/cadmium sulfide (CdTe/CdS) ultrasmall quantum dots (QDs) have high fluorescent quantum yield, long fluorescence lifetime and long half-life in blood, allowing high resolution long-term intravital vascular imaging. In this study, we showed that these QDs can be used to visualize the in vivo the vasculature in normal and cancerous livers in mice using multiphoton microscopy (MPM) coupled with fluorescence lifetime imaging (FLIM), with cellular resolution (~1 µm) up to 36 h after intravenous injection. Compared to highly regulated and controlled sinusoids in normal liver tissue, disordered, tortuous, and immature neovessels were observed in tumors. The utilized imaging methods have great potential as emerging tools in diagnosis and monitoring of treatment response in cancer. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessArticle
Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma
Pharmaceutics 2018, 10(4), 226; https://doi.org/10.3390/pharmaceutics10040226 - 10 Nov 2018
Cited by 5
Abstract
Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), [...] Read more.
Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessArticle
Preparation of Reduction-Responsive Camptothecin Nanocapsules by Combining Nanoprecipitation and In Situ Polymerization for Anticancer Therapy
Pharmaceutics 2018, 10(4), 173; https://doi.org/10.3390/pharmaceutics10040173 - 03 Oct 2018
Cited by 4
Abstract
Stimuli-responsive systems for controlled drug release have been extensively explored in recent years. In this work, we developed a reduction-responsive camptothecin (CPT) nanocapsule (CPT-NC) by combining nanoprecipitation and in situ polymerization using a polymerized surface ligand and a disulfide bond-containing crosslinker. Dissolution rate [...] Read more.
Stimuli-responsive systems for controlled drug release have been extensively explored in recent years. In this work, we developed a reduction-responsive camptothecin (CPT) nanocapsule (CPT-NC) by combining nanoprecipitation and in situ polymerization using a polymerized surface ligand and a disulfide bond-containing crosslinker. Dissolution rate studies proved that the CPT-NCs have robust drug-release profiles in the presence of glutathione (GSH) owing to the division of the disulfide bond crosslinker which triggers the collapse of the polymer layer. Furthermore, the in vitro investigations demonstrated that the CPT-NCs exhibited a high-cellular uptake efficiency and cytotoxicity for cancer cells of squamous cell carcinoma (SCC-15). Our approach thus presents an effective intracellular drug delivery strategy for anticancer therapy. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Review

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Open AccessReview
Computational Approaches in Theranostics: Mining and Predicting Cancer Data
Pharmaceutics 2019, 11(3), 119; https://doi.org/10.3390/pharmaceutics11030119 - 13 Mar 2019
Cited by 7
Abstract
The ability to understand the complexity of cancer-related data has been prompted by the applications of (1) computer and data sciences, including data mining, predictive analytics, machine learning, and artificial intelligence, and (2) advances in imaging technology and probe development. Computational modelling and [...] Read more.
The ability to understand the complexity of cancer-related data has been prompted by the applications of (1) computer and data sciences, including data mining, predictive analytics, machine learning, and artificial intelligence, and (2) advances in imaging technology and probe development. Computational modelling and simulation are systematic and cost-effective tools able to identify important temporal/spatial patterns (and relationships), characterize distinct molecular features of cancer states, and address other relevant aspects, including tumor detection and heterogeneity, progression and metastasis, and drug resistance. These approaches have provided invaluable insights for improving the experimental design of therapeutic delivery systems and for increasing the translational value of the results obtained from early and preclinical studies. The big question is: Could cancer theranostics be determined and controlled in silico? This review describes the recent progress in the development of computational models and methods used to facilitate research on the molecular basis of cancer and on the respective diagnosis and optimized treatment, with particular emphasis on the design and optimization of theranostic systems. The current role of computational approaches is providing innovative, incremental, and complementary data-driven solutions for the prediction, simplification, and characterization of cancer and intrinsic mechanisms, and to promote new data-intensive, accurate diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
A Review on (Hydro)Porphyrin-Loaded Polymer Micelles: Interesting and Valuable Platforms for Enhanced Cancer Nanotheranostics
Pharmaceutics 2019, 11(2), 81; https://doi.org/10.3390/pharmaceutics11020081 - 15 Feb 2019
Cited by 1
Abstract
Porphyrins are known therapeutic agents for photodynamic therapy of cancer and also imaging agents for NIR fluorescence imaging, MRI, or PET. A combination of interesting features makes tetrapyrrolic macrocycles suitable for use as theranostic agents whose full potential can be achieved using nanocarriers. [...] Read more.
Porphyrins are known therapeutic agents for photodynamic therapy of cancer and also imaging agents for NIR fluorescence imaging, MRI, or PET. A combination of interesting features makes tetrapyrrolic macrocycles suitable for use as theranostic agents whose full potential can be achieved using nanocarriers. This review provides an overview on nanotheranostic agents based on polymeric micelles and porphyrins developed so far. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems
Pharmaceutics 2019, 11(1), 22; https://doi.org/10.3390/pharmaceutics11010022 - 08 Jan 2019
Cited by 41
Abstract
Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related [...] Read more.
Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting. Particularly recognizing the increased complexity and multimodality in this area, multifunctional hybrid nanoparticles, comprising different nanomaterials and functionalized with targeting moieties and/or anticancer drugs, present the best characteristics for theranostics. Several examples, focusing on their design, composition, imaging and treatment modalities, and in vitro and in vivo characterization, are detailed herein. Briefly, all studies followed a common trend in the design of these theranostics modalities, such as the use of materials and/or drugs that share both inherent imaging (e.g., contrast agents) and therapeutic properties (e.g., heating or production reactive oxygen species). This rationale allows one to apparently overcome the heterogeneity, complexity, and harsh conditions of tumor microenvironments, leading to the development of successful targeted therapies. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics
Pharmaceutics 2018, 10(4), 282; https://doi.org/10.3390/pharmaceutics10040282 - 16 Dec 2018
Cited by 9
Abstract
Many graphene-based materials (GBNs) applied to therapy and diagnostics (theranostics) in cancer have been developed. Most of them are hybrid combinations of graphene with other components (e.g., drugs or other bioactives, polymers, and nanoparticles) aiming toward a synergic theranostic effect. However, the role [...] Read more.
Many graphene-based materials (GBNs) applied to therapy and diagnostics (theranostics) in cancer have been developed. Most of them are hybrid combinations of graphene with other components (e.g., drugs or other bioactives, polymers, and nanoparticles) aiming toward a synergic theranostic effect. However, the role of graphene in each of these hybrids is sometimes not clear enough and the synergic graphene effect is not proven. The objective of this review is to elaborate on the role of GBNs in the studies evaluated and to compare the nanoformulations in terms of some of their characteristics, such as therapeutic outcomes and toxicity, which are essential features for their potential use as bionanosystems. A systematic review was carried out using the following databases: PubMed, Scopus, and ISI Web of Science (2013–2018). Additional studies were identified manually by consulting the references list of relevant reviews. Only English papers presenting at least one strategy for cancer therapy and one strategy for cancer diagnostics, and that clearly show the role of graphene in theranostics, were included. Data extraction and quality assessment was made by reviewer pairings. Fifty-five studies met the inclusion criteria, but they were too heterogeneous to combine in statistical meta-analysis. Critical analysis and discussion of the selected papers are presented. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
Overview of DNA Self-Assembling: Progresses in Biomedical Applications
Pharmaceutics 2018, 10(4), 268; https://doi.org/10.3390/pharmaceutics10040268 - 11 Dec 2018
Cited by 6
Abstract
Molecular self-assembling is ubiquitous in nature providing structural and functional machinery for the cells. In recent decades, material science has been inspired by the nature’s assembly principles to create artificially higher-order structures customized with therapeutic and targeting molecules, organic and inorganic fluorescent probes [...] Read more.
Molecular self-assembling is ubiquitous in nature providing structural and functional machinery for the cells. In recent decades, material science has been inspired by the nature’s assembly principles to create artificially higher-order structures customized with therapeutic and targeting molecules, organic and inorganic fluorescent probes that have opened new perspectives for biomedical applications. Among these novel man-made materials, DNA nanostructures hold great promise for the modular assembly of biocompatible molecules at the nanoscale of multiple shapes and sizes, designed via molecular programming languages. Herein, we summarize the recent advances made in the designing of DNA nanostructures with special emphasis on their application in biomedical research as imaging and diagnostic platforms, drug, gene, and protein vehicles, as well as theranostic agents that are meant to operate in-cell and in-vivo. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
Targeted Theranostic Nanoparticles for Brain Tumor Treatment
Pharmaceutics 2018, 10(4), 181; https://doi.org/10.3390/pharmaceutics10040181 - 09 Oct 2018
Cited by 35
Abstract
The poor prognosis and rapid recurrence of glioblastoma (GB) are associated to its fast-growing process and invasive nature, which make difficult the complete removal of the cancer infiltrated tissues. Additionally, GB heterogeneity within and between patients demands a patient-focused method of treatment. Thus, [...] Read more.
The poor prognosis and rapid recurrence of glioblastoma (GB) are associated to its fast-growing process and invasive nature, which make difficult the complete removal of the cancer infiltrated tissues. Additionally, GB heterogeneity within and between patients demands a patient-focused method of treatment. Thus, the implementation of nanotechnology is an attractive approach considering all anatomic issues of GB, since it will potentially improve brain drug distribution, due to the interaction between the blood–brain barrier and nanoparticles (NPs). In recent years, theranostic techniques have also been proposed and regarded as promising. NPs are advantageous for this application, due to their respective size, easy surface modification and versatility to integrate multiple functional components in one system. The design of nanoparticles focused on therapeutic and diagnostic applications has increased exponentially for the treatment of cancer. This dual approach helps to understand the location of the tumor tissue, the biodistribution of nanoparticles, the progress and efficacy of the treatment, and is highly useful for personalized medicine-based therapeutic interventions. To improve theranostic approaches, different active strategies can be used to modulate the surface of the nanotheranostic particle, including surface markers, proteins, drugs or genes, and take advantage of the characteristics of the microenvironment using stimuli responsive triggers. This review focuses on the different strategies to improve the GB treatment, describing some cell surface markers and their ligands, and reports some strategies, and their efficacy, used in the current research. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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Open AccessReview
Magnetogels: Prospects and Main Challenges in Biomedical Applications
Pharmaceutics 2018, 10(3), 145; https://doi.org/10.3390/pharmaceutics10030145 - 04 Sep 2018
Cited by 9
Abstract
Drug delivery nanosystems have been thriving in recent years as a promising application in therapeutics, seeking to solve the lack of specificity of conventional chemotherapy targeting and add further features such as enhanced magnetic resonance imaging, biosensing and hyperthermia. The combination of magnetic [...] Read more.
Drug delivery nanosystems have been thriving in recent years as a promising application in therapeutics, seeking to solve the lack of specificity of conventional chemotherapy targeting and add further features such as enhanced magnetic resonance imaging, biosensing and hyperthermia. The combination of magnetic nanoparticles and hydrogels introduces a new generation of nanosystems, the magnetogels, which combine the advantages of both nanomaterials, apart from showing interesting properties unobtainable when both systems are separated. The presence of magnetic nanoparticles allows the control and targeting of the nanosystem to a specific location by an externally applied magnetic field gradient. Moreover, the application of an alternating magnetic field (AMF) not only allows therapy through hyperthermia, but also enhances drug delivery and chemotherapeutic desired effects, which combined with the hydrogel specificity, confer a high therapeutic efficiency. Therefore, the present review summarizes the magnetogels properties and critically discusses their current and recent biomedical applications, apart from an outlook on future goals and perspectives. Full article
(This article belongs to the Special Issue Nanotheranostics and Cancer: Where Are We Now?)
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