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9 pages, 6136 KiB

Open AccessArticle

Magnetic Mixed Micelles Composed of a Non-Ionic Surfactant and Nitroxide Radicals Containing a d-Glucosamine Unit: Preparation, Stability, and Biomedical Application

by Kota Nagura, Yusa Takemoto, Fumi Yoshino, Alexey Bogdanov, Natalia Chumakova, Andrey Kh. Vorobiev, Hirohiko Imai, Tetsuya Matsuda, Satoshi Shimono, Tatsuhisa Kato, Naoki Komatsu and Rui Tamura

Pharmaceutics 2019, 11(1), 42; https://doi.org/10.3390/pharmaceutics11010042 - 19 Jan 2019

Cited by 6 | Viewed by 3693

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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11 pages, 2131 KiB

Open AccessArticle

HSA—Coated Magnetic Nanoparticles for MRI-Guided Photodynamic Cancer Therapy

by Petr Ostroverkhov, Alevtina Semkina, Victor Naumenko, Ekaterina Plotnikova, Raisa Yakubovskaya, Stepan Vodopyanov, Artem Abakumov, Alexander Majouga, Michael Grin, Vladimir Chekhonin and Maxim Abakumov

Pharmaceutics 2018, 10(4), 284; https://doi.org/10.3390/pharmaceutics10040284 - 17 Dec 2018

Cited by 14 | Viewed by 5422

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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8 pages, 2085 KiB

Open AccessCommunication

Anionic Long-Circulating Quantum Dots for Long-Term Intravital Vascular Imaging

by Haolu Wang, Haotian Yang, Zhi Ping Xu, Xin Liu, Michael S. Roberts and Xiaowen Liang

Pharmaceutics 2018, 10(4), 244; https://doi.org/10.3390/pharmaceutics10040244 - 20 Nov 2018

Cited by 12 | Viewed by 2918

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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18 pages, 3186 KiB

Open AccessArticle

Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma

by Janel Kydd, Rahul Jadia and Prakash Rai

Pharmaceutics 2018, 10(4), 226; https://doi.org/10.3390/pharmaceutics10040226 - 10 Nov 2018

Cited by 12 | Viewed by 4276

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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12 pages, 3769 KiB

Open AccessArticle

Preparation of Reduction-Responsive Camptothecin Nanocapsules by Combining Nanoprecipitation and In Situ Polymerization for Anticancer Therapy

by Xiao-Qing Song, Cheng Tao, Wei Li, Jie-Xin Wang, Yuan Le and Jian-Jun Zhang

Pharmaceutics 2018, 10(4), 173; https://doi.org/10.3390/pharmaceutics10040173 - 03 Oct 2018

Cited by 10 | Viewed by 3675

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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28 pages, 7428 KiB

Open AccessReview

Computational Approaches in Theranostics: Mining and Predicting Cancer Data

by Tânia F. G. G. Cova, Daniel J. Bento and Sandra C. C. Nunes

Pharmaceutics 2019, 11(3), 119; https://doi.org/10.3390/pharmaceutics11030119 - 13 Mar 2019

Cited by 16 | Viewed by 4758

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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23 pages, 7625 KiB

Open AccessReview

A Review on (Hydro)Porphyrin-Loaded Polymer Micelles: Interesting and Valuable Platforms for Enhanced Cancer Nanotheranostics

by Bruno F. O. Nascimento, Nelson A. M. Pereira, Artur J. M. Valente, Teresa M. V. D. Pinho e Melo and Marta Pineiro

Pharmaceutics 2019, 11(2), 81; https://doi.org/10.3390/pharmaceutics11020081 - 15 Feb 2019

Cited by 10 | Viewed by 4484

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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40 pages, 2237 KiB

Open AccessReview

Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems

by Catarina Oliveira Silva, Jacinta Oliveira Pinho, Joana Margarida Lopes, António J. Almeida, Maria Manuela Gaspar and Catarina Reis

Pharmaceutics 2019, 11(1), 22; https://doi.org/10.3390/pharmaceutics11010022 - 08 Jan 2019

Cited by 144 | Viewed by 12075

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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45 pages, 2003 KiB

Open AccessReview

A Systematic Review and Critical Analysis of the Role of Graphene-Based Nanomaterials in Cancer Theranostics

by Teresa Viseu, Carla M. Lopes, Eduarda Fernandes, Maria Elisabete C.D. Real Oliveira and Marlene Lúcio

Pharmaceutics 2018, 10(4), 282; https://doi.org/10.3390/pharmaceutics10040282 - 16 Dec 2018

Cited by 28 | Viewed by 4937

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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41 pages, 4834 KiB

Open AccessReview

Overview of DNA Self-Assembling: Progresses in Biomedical Applications

by Andreia F. Jorge and Ramon Eritja

Pharmaceutics 2018, 10(4), 268; https://doi.org/10.3390/pharmaceutics10040268 - 11 Dec 2018

Cited by 20 | Viewed by 5219

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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47 pages, 6106 KiB

Open AccessReview

Targeted Theranostic Nanoparticles for Brain Tumor Treatment

by Maria Mendes, João José Sousa, Alberto Pais and Carla Vitorino

Pharmaceutics 2018, 10(4), 181; https://doi.org/10.3390/pharmaceutics10040181 - 09 Oct 2018

Cited by 83 | Viewed by 9154

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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23 pages, 2911 KiB

Open AccessReview

Magnetogels: Prospects and Main Challenges in Biomedical Applications

by Sérgio R. S. Veloso, Paula M. T. Ferreira, J. A. Martins, Paulo J. G. Coutinho and Elisabete M. S. Castanheira

Pharmaceutics 2018, 10(3), 145; https://doi.org/10.3390/pharmaceutics10030145 - 04 Sep 2018

Cited by 28 | Viewed by 5726

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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