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3 pages, 190 KiB

Open AccessEditorial

Special Issue “Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions”

by Okhil K. Nag and James B. Delehanty

Pharmaceuticals 2023, 16(10), 1344; https://doi.org/10.3390/ph16101344 - 22 Sep 2023

Viewed by 950

Abstract

Over the past several decades, nanoparticles (NPs) have shown promising capabilities in the field of medicine for their applications as vehicles for targeted drug delivery [...] Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

Research

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14 pages, 2139 KiB

Open AccessArticle

Liquid Crystal Nanoparticle Conjugates for Scavenging Reactive Oxygen Species in Live Cells

by Okhil K. Nag, Jawad Naciri, Kwahun Lee, Eunkeu Oh, Bethany Almeida and James B. Delehanty

Pharmaceuticals 2022, 15(5), 604; https://doi.org/10.3390/ph15050604 - 14 May 2022

Cited by 5 | Viewed by 2286

Abstract

The elevated intracellular production of or extracellular exposure to reactive oxygen species (ROS) causes oxidative stress to cells, resulting in deleterious irreversible biomolecular reactions (e.g., lipid peroxidation) and disease progression. The use of low-molecular weight antioxidants, such as 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), as ROS scavengers [...] Read more.

The elevated intracellular production of or extracellular exposure to reactive oxygen species (ROS) causes oxidative stress to cells, resulting in deleterious irreversible biomolecular reactions (e.g., lipid peroxidation) and disease progression. The use of low-molecular weight antioxidants, such as 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), as ROS scavengers fails to achieve the desired efficacy because of their poor or uncontrolled cellular uptake and off-target effects, such as dysfunction of essential redox homeostasis. In this study, we fabricated a liquid crystal nanoparticle (LCNP) conjugate system with the fluorescent dye perylene (PY) loaded in the interior and poly (ethylene glycol) (PEG) decorated on the surface along with multiple molecules of TEMPO (PY-LCNP-PEG/TEMPO). PY-LCNP-PEG/TEMPO exhibit enhanced cellular uptake, and efficient ROS-scavenging activity in live cells. On average, the 120 nm diameter PY-LCNPs were conjugated with >1800 molecules of TEMPO moieties on their surface. PY-LCNP-PEG/TEMPO showed significantly greater reduction in ROS activity and lipid peroxidation compared to free TEMPO when the cells were challenged with ROS generating agents, such as hydrogen peroxide (H₂O₂). We suggest that this is due to the increased local concentration of TEMPO molecules on the surface of the PY-LCNP-PEG/TEMPO NPs, which efficiently bind to the plasma membrane and enter cells. Overall, these results demonstrate the enhanced capability of TEMPO-conjugated LCNPs to protect live cells from oxidative stress by effectively scavenging ROS and reducing lipid peroxidation. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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19 pages, 5175 KiB

Open AccessArticle

CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles

by Enrica Chiesa, Antonietta Greco, Federica Riva, Rossella Dorati, Bice Conti, Tiziana Modena and Ida Genta

Pharmaceuticals 2022, 15(1), 103; https://doi.org/10.3390/ph15010103 - 17 Jan 2022

Cited by 27 | Viewed by 8221

Abstract

Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is [...] Read more.

Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs’ internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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18 pages, 3382 KiB

Open AccessArticle

Preparation of Multifunctional N-Doped Carbon Quantum Dots from Citrus clementina Peel: Investigating Targeted Pharmacological Activities and the Potential Application for Fe³⁺ Sensing

by Silvija Šafranko, Anamarija Stanković, Sugato Hajra, Hoe-Joon Kim, Ivica Strelec, Maja Dutour-Sikirić, Igor Weber, Maja Herak Bosnar, Petra Grbčić, Sandra Kraljević Pavelić, Aleksandar Széchenyi, Yogendra Kumar Mishra, Igor Jerković and Stela Jokić

Pharmaceuticals 2021, 14(9), 857; https://doi.org/10.3390/ph14090857 - 27 Aug 2021

Cited by 40 | Viewed by 5091

Abstract

Carbon quantum dots (CQDs) have recently emerged as innovative theranostic nanomaterials, enabling fast and effective diagnosis and treatment. In this study, a facile hydrothermal approach for N-doped biomass-derived CQDs preparation from Citrus clementina peel and amino acids glycine (Gly) and arginine (Arg) has [...] Read more.

Carbon quantum dots (CQDs) have recently emerged as innovative theranostic nanomaterials, enabling fast and effective diagnosis and treatment. In this study, a facile hydrothermal approach for N-doped biomass-derived CQDs preparation from Citrus clementina peel and amino acids glycine (Gly) and arginine (Arg) has been presented. The gradual increase in the N-dopant (amino acids) nitrogen content increased the quantum yield of synthesized CQDs. The prepared CQDs exhibited good biocompatibility, stability in aqueous, and high ionic strength media, similar optical properties, while differences were observed regarding the structural and chemical diversity, and biological and antioxidant activity. The antiproliferative effect of CQD@Gly against pancreatic cancer cell lines (CFPAC-1) was observed. At the same time, CQD@Arg has demonstrated the highest quantum yield and antioxidant activity by DPPH scavenging radical method of 81.39 ± 0.39% and has been further used for the ion sensing and cellular imaging of cancer cells. The obtained results have demonstrated selective response toward Fe³⁺ detection, with linear response ranging from 7.0 µmol dm⁻³ to 50.0 µmol dm⁻³ with R² = 0.9931 and limit of detection (LOD) of 4.57 ± 0.27 µmol dm⁻³. This research could be a good example of sustainable biomass waste utilization with potential for biomedical analysis and ion sensing applications. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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19 pages, 4606 KiB

Open AccessArticle

Tumor-Targeted Fluorescent Proteinoid Nanocapsules Encapsulating Synergistic Drugs for Personalized Cancer Therapy

by Ella Itzhaki, Elad Hadad, Neta Moskovits, Salomon M. Stemmer and Shlomo Margel

Pharmaceuticals 2021, 14(7), 648; https://doi.org/10.3390/ph14070648 - 6 Jul 2021

Cited by 6 | Viewed by 3129

Abstract

Personalized cancer treatment based on specific mutations offers targeted therapy and is preferred over “standard” chemotherapy. Proteinoid polymers produced by thermal step-growth polymerization of amino acids may form nanocapsules (NCs) that encapsulate drugs overcoming miscibility problems and allowing passive targeted delivery with reduced [...] Read more.

Personalized cancer treatment based on specific mutations offers targeted therapy and is preferred over “standard” chemotherapy. Proteinoid polymers produced by thermal step-growth polymerization of amino acids may form nanocapsules (NCs) that encapsulate drugs overcoming miscibility problems and allowing passive targeted delivery with reduced side effects. The arginine-glycine-glutamic acid (RGD) sequence is known for its preferential attraction to αvβ3 integrin, which is highly expressed on neovascular endothelial cells that support tumor growth. Here, tumor-targeted RGD-based proteinoid NCs entrapping a synergistic combination of Palbociclib (Pal) and Alpelisib (Alp) were synthesized by self-assembly to induce the reduction of tumor cell growth in different types of cancers. The diameters of the hollow and drug encapsulating poly(RGD) NCs were 34 ± 5 and 22 ± 3 nm, respectively; thereby, their drug targeted efficiency is due to both passive and active targeting. The encapsulation yield of Pal and Alp was 70 and 90%, respectively. In vitro experiments with A549, MCF7 and HCT116 human cancer cells demonstrate a synergistic effect of Pal and Alp, controlled release and dose dependence. Preliminary results in a 3D tumor spheroid model with cells derived from patient-derived xenografts of colon cancer illustrate disassembly of spheroids, indicating that the NCs have therapeutic potential. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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17 pages, 4793 KiB

Open AccessArticle

Bare Iron Oxide Nanoparticles as Drug Delivery Carrier for the Short Cationic Peptide Lasioglossin

by Chiara Turrina, Sonja Berensmeier and Sebastian P. Schwaminger

Pharmaceuticals 2021, 14(5), 405; https://doi.org/10.3390/ph14050405 - 24 Apr 2021

Cited by 34 | Viewed by 4873

Abstract

New drug delivery systems are a potential solution for administering drugs to reduce common side effects of traditional methods, such as in cancer therapy. Iron oxide nanoparticles (IONs) can increase the drugs’ biological activity through high binding efficiency and magnetically targeted drug delivery. [...] Read more.

New drug delivery systems are a potential solution for administering drugs to reduce common side effects of traditional methods, such as in cancer therapy. Iron oxide nanoparticles (IONs) can increase the drugs’ biological activity through high binding efficiency and magnetically targeted drug delivery. Understanding the adsorption and release process of a drug to the carrier material plays a significant role in research to generate an applicable and controlled drug delivery system. This contribution focuses on the binding patterns of the peptide lasioglossin III from bee venom on bare IONs. Lasioglossin has a high antimicrobial behavior and due to its cationic properties, it has high binding potential. Considering the influence of pH, the buffer type, the particle concentration, and time, the highest drug loading of 22.7% is achieved in phosphate-buffered saline. Analysis of the desorption conditions revealed temperature and salt concentration sensitivity. The nanoparticles and peptide-ION complexes are analyzed with dynamic light scattering, zeta potential, and infrared spectroscopy. Additionally, cytotoxicity experiments performed on Escherichia coli show higher antimicrobial activity of bound lasioglossin than of the free peptide. Therefore, bare IONs are an interesting platform material for the development of drug-delivery carriers for cationic peptides. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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13 pages, 3300 KiB

Open AccessArticle

Highly Efficient T2 Cobalt Ferrite Nanoparticles Vectorized for Internalization in Cancer Cells

by Eva Mazarío, Magdalena Cañete, Fernando Herranz, Jorge Sánchez-Marcos, Jesús M. de la Fuente, Pilar Herrasti and Nieves Menéndez

Pharmaceuticals 2021, 14(2), 124; https://doi.org/10.3390/ph14020124 - 5 Feb 2021

Cited by 9 | Viewed by 2574

Abstract

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the [...] Read more.

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM⁻¹s⁻¹ of transverse relaxivity (r₂) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI). Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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20 pages, 2111 KiB

Open AccessArticle

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice

by Mohamed A. Safwat, Bothaina A. Kandil, Mohamed A. Elblbesy, Ghareb M. Soliman and Nermin E. Eleraky

Pharmaceuticals 2020, 13(9), 254; https://doi.org/10.3390/ph13090254 - 18 Sep 2020

Cited by 30 | Viewed by 3706

Abstract

Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood [...] Read more.

Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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Review

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31 pages, 5217 KiB

Open AccessEditor’s ChoiceReview

Theranostic Nanomedicines for the Treatment of Cardiovascular and Related Diseases: Current Strategies and Future Perspectives

by Natasha Manners, Vishnu Priya, Abhishesh Kumar Mehata, Manoj Rawat, Syam Mohan, Hafiz A. Makeen, Mohammed Albratty, Ali Albarrati, Abdulkarim M. Meraya and Madaswamy S. Muthu

Pharmaceuticals 2022, 15(4), 441; https://doi.org/10.3390/ph15040441 - 1 Apr 2022

Cited by 18 | Viewed by 4622

Abstract

Cardiovascular and related diseases (CVRDs) are among the most prevalent chronic diseases in the 21st century, with a high mortality rate. This review summarizes the various nanomedicines for diagnostic and therapeutic applications in CVRDs, including nanomedicine for angina pectoris, myocarditis, myocardial infarction, pericardial [...] Read more.

Cardiovascular and related diseases (CVRDs) are among the most prevalent chronic diseases in the 21st century, with a high mortality rate. This review summarizes the various nanomedicines for diagnostic and therapeutic applications in CVRDs, including nanomedicine for angina pectoris, myocarditis, myocardial infarction, pericardial disorder, thrombosis, atherosclerosis, hyperlipidemia, hypertension, pulmonary arterial hypertension and stroke. Theranostic nanomedicines can prolong systemic circulation, escape from the host defense system, and deliver theranostic agents to the targeted site for imaging and therapy at a cellular and molecular level. Presently, discrete non-invasive and non-surgical theranostic methodologies are such an advancement modality capable of targeted diagnosis and therapy and have better efficacy with fewer side effects than conventional medicine. Additionally, we have presented the recent updates on nanomedicine in clinical trials, targeted nanomedicine and its translational challenges for CVRDs. Theranostic nanomedicine acts as a bridge towards CVRDs amelioration and its management. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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29 pages, 535 KiB

Open AccessReview

Nanoparticles in Dentistry: A Comprehensive Review

by Gustavo Moraes, Carolina Zambom and Walter L. Siqueira

Pharmaceuticals 2021, 14(8), 752; https://doi.org/10.3390/ph14080752 - 30 Jul 2021

Cited by 34 | Viewed by 6826

Abstract

In recent years, nanoparticles (NPs) have been receiving more attention in dentistry. Their advantageous physicochemical and biological properties can improve the diagnosis, prevention, and treatment of numerous oral diseases, including dental caries, periodontal diseases, pulp and periapical lesions, oral candidiasis, denture stomatitis, hyposalivation, [...] Read more.

In recent years, nanoparticles (NPs) have been receiving more attention in dentistry. Their advantageous physicochemical and biological properties can improve the diagnosis, prevention, and treatment of numerous oral diseases, including dental caries, periodontal diseases, pulp and periapical lesions, oral candidiasis, denture stomatitis, hyposalivation, and head, neck, and oral cancer. NPs can also enhance the mechanical and microbiological properties of dental prostheses and implants and can be used to improve drug delivery through the oral mucosa. This paper reviewed studies from 2015 to 2020 and summarized the potential applications of different types of NPs in the many fields of dentistry. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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18 pages, 3802 KiB

Open AccessReview

Transgene Delivery to Human Induced Pluripotent Stem Cells Using Nanoparticles

by Megan A. Yamoah, Phung N. Thai and Xiao-Dong Zhang

Pharmaceuticals 2021, 14(4), 334; https://doi.org/10.3390/ph14040334 - 6 Apr 2021

Cited by 4 | Viewed by 6961

Abstract

Human induced pluripotent stem cells (hiPSCs) and hiPSCs-derived cells have the potential to revolutionize regenerative and precision medicine. Genetically reprograming somatic cells to generate hiPSCs and genetic modification of hiPSCs are considered the key procedures for the study and application of hiPSCs. However, [...] Read more.

Human induced pluripotent stem cells (hiPSCs) and hiPSCs-derived cells have the potential to revolutionize regenerative and precision medicine. Genetically reprograming somatic cells to generate hiPSCs and genetic modification of hiPSCs are considered the key procedures for the study and application of hiPSCs. However, there are significant technical challenges for transgene delivery into somatic cells and hiPSCs since these cells are known to be difficult to transfect. The existing methods, such as viral transduction and chemical transfection, may introduce significant alternations to hiPSC culture which affect the potency, purity, consistency, safety, and functional capacity of hiPSCs. Therefore, generation and genetic modification of hiPSCs through non-viral approaches are necessary and desirable. Nanotechnology has revolutionized fields from astrophysics to biology over the past two decades. Increasingly, nanoparticles have been used in biomedicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics. The most successful example is the recent development of SARS-CoV-2 vaccines at warp speed to combat the 2019 coronavirus disease (COVID-19), which brought nanoparticles to the center stage of biomedicine and demonstrated the efficient nanoparticle-mediated transgene delivery into human body. Nanoparticles have the potential to facilitate the transgene delivery into the hiPSCs and offer a simple and robust approach. Nanoparticle-mediated transgene delivery has significant advantages over other methods, such as high efficiency, low cytotoxicity, biodegradability, low cost, directional and distal controllability, efficient in vivo applications, and lack of immune responses. Our recent study using magnetic nanoparticles for transfection of hiPSCs provided an example of the successful applications, supporting the potential roles of nanoparticles in hiPSC biology. This review discusses the principle, applications, and significance of nanoparticles in the transgene delivery to hiPSCs and their successful application in the development of COVID-19 vaccines. Full article

(This article belongs to the Special Issue Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions)

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