Editorial

3 pages, 183 KiB

Open AccessEditorial

Nanomaterials for Drug Delivery and Cancer Therapy

by Fiore Pasquale Nicoletta and Francesca Iemma

Nanomaterials 2023, 13(1), 207; https://doi.org/10.3390/nano13010207 - 03 Jan 2023

Cited by 2 | Viewed by 1826

In recent decades, the interest in nanomaterials has grown rapidly for their applications in many research fields, including drug delivery and cancer therapy [...] Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

Research

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22 pages, 2953 KiB

Open AccessEditor’s ChoiceArticle

Anti-Fn14-Conjugated Prussian Blue Nanoparticles as a Targeted Photothermal Therapy Agent for Glioblastoma

by Nicole F. Bonan, Debbie K. Ledezma, Matthew A. Tovar, Preethi B. Balakrishnan and Rohan Fernandes

Nanomaterials 2022, 12(15), 2645; https://doi.org/10.3390/nano12152645 - 01 Aug 2022

Cited by 9 | Viewed by 2304

Abstract

Prussian blue nanoparticles (PBNPs) are effective photothermal therapy (PTT) agents: they absorb near-infrared radiation and reemit it as heat via phonon-phonon relaxations that, in the presence of tumors, can induce thermal and immunogenic cell death. However, in the context of central nervous system [...] Read more.

Prussian blue nanoparticles (PBNPs) are effective photothermal therapy (PTT) agents: they absorb near-infrared radiation and reemit it as heat via phonon-phonon relaxations that, in the presence of tumors, can induce thermal and immunogenic cell death. However, in the context of central nervous system (CNS) tumors, the off-target effects of PTT have the potential to result in injury to healthy CNS tissue. Motivated by this need for targeted PTT agents for CNS tumors, we present a PBNP formulation that targets fibroblast growth factor-inducible 14 (Fn14)-expressing glioblastoma cell lines. We conjugated an antibody targeting Fn14, a receptor abundantly expressed on many glioblastomas but near absent on healthy CNS tissue, to PBNPs (aFn14-PBNPs). We measured the attachment efficiency of aFn14 onto PBNPs, the size and stability of aFn14-PBNPs, and the ability of aFn14-PBNPs to induce thermal and immunogenic cell death and target and treat glioblastoma tumor cells in vitro. aFn14 remained stably conjugated to the PBNPs for at least 21 days. Further, PTT with aFn14-PBNPs induced thermal and immunogenic cell death in glioblastoma tumor cells. However, in a targeted treatment assay, PTT was only effective in killing glioblastoma tumor cells when using aFn14-PBNPs, not when using PBNPs alone. Our methodology is novel in its targeting moiety, tumor application, and combination with PTT. To the best of our knowledge, PBNPs have not been investigated as a targeted PTT agent in glioblastoma via conjugation to aFn14. Our results demonstrate a novel and effective method for delivering targeted PTT to aFn14-expressing tumor cells via aFn14 conjugation to PBNPs. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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8 pages, 12408 KiB

Open AccessArticle

Analysis of Fluorescence Decay Kinetics of Indocyanine Green Monomers and Aggregates in Brain Tumor Model In Vivo

by Dina Farrakhova, Igor Romanishkin, Yuliya Maklygina, Lina Bezdetnaya and Victor Loschenov

Nanomaterials 2021, 11(12), 3185; https://doi.org/10.3390/nano11123185 - 24 Nov 2021

Cited by 7 | Viewed by 1580

Abstract

Spectroscopic approach with fluorescence time resolution allows one to determine the state of a brain tumor and its microenvironment via changes in the fluorescent dye’s fluorescence lifetime. Indocyanine green (ICG) is an acknowledged infra-red fluorescent dye that self-assembles into stable aggregate forms (ICG [...] Read more.

Spectroscopic approach with fluorescence time resolution allows one to determine the state of a brain tumor and its microenvironment via changes in the fluorescent dye’s fluorescence lifetime. Indocyanine green (ICG) is an acknowledged infra-red fluorescent dye that self-assembles into stable aggregate forms (ICG NPs). ICG NPs aggregates have a tendency to accumulate in the tumor with a maximum accumulation at 24 h after systemic administration, enabling extended intraoperative diagnostic. Fluorescence lifetime analysis of ICG and ICG NPs demonstrates different values for ICG monomers and H-aggregates, indicating promising suitability for fluorescent diagnostics of brain tumors due to their affinity to tumor cells and stability in biological tissue. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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14 pages, 2123 KiB

Open AccessEditor’s ChoiceArticle

Combining Augmented Radiotherapy and Immunotherapy through a Nano-Gold and Bacterial Outer-Membrane Vesicle Complex for the Treatment of Glioblastoma

by Mei-Hsiu Chen, Tse-Ying Liu, Yu-Chiao Chen and Ming-Hong Chen

Nanomaterials 2021, 11(7), 1661; https://doi.org/10.3390/nano11071661 - 24 Jun 2021

Cited by 31 | Viewed by 3499

Abstract

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing [...] Read more.

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-

α

production. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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16 pages, 14648 KiB

Open AccessEditor’s ChoiceArticle

Modulation of Macrophage Polarization by Carbon Nanodots and Elucidation of Carbon Nanodot Uptake Routes in Macrophages

by Andrew Dunphy, Kamal Patel, Sarah Belperain, Aubrey Pennington, Norman H. L. Chiu, Ziyu Yin, Xuewei Zhu, Brandon Priebe, Shaomin Tian, Jianjun Wei, Xianwen Yi and Zhenquan Jia

Nanomaterials 2021, 11(5), 1116; https://doi.org/10.3390/nano11051116 - 26 Apr 2021

Cited by 7 | Viewed by 2526

Abstract

Atherosclerosis represents an ever-present global concern, as it is a leading cause of cardiovascular disease and an immense public welfare issue. Macrophages play a key role in the onset of the disease state and are popular targets in vascular research and therapeutic treatment. [...] Read more.

Atherosclerosis represents an ever-present global concern, as it is a leading cause of cardiovascular disease and an immense public welfare issue. Macrophages play a key role in the onset of the disease state and are popular targets in vascular research and therapeutic treatment. Carbon nanodots (CNDs) represent a type of carbon-based nanomaterial and have garnered attention in recent years for potential in biomedical applications. This investigation serves as a foremost attempt at characterizing the interplay between macrophages and CNDs. We have employed THP-1 monocyte-derived macrophages as our target cell line representing primary macrophages in the human body. Our results showcase that CNDs are non-toxic at a variety of doses. THP-1 monocytes were differentiated into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and co-treatment with 0.1 mg/mL CNDs. This co-treatment significantly increased the expression of CD 206 and CD 68 (key receptors involved in phagocytosis) and increased the expression of CCL2 (a monocyte chemoattractant and pro-inflammatory cytokine). The phagocytic activity of THP-1 monocyte-derived macrophages co-treated with 0.1 mg/mL CNDs also showed a significant increase. Furthermore, this study also examined potential entrance routes of CNDs into macrophages. We have demonstrated an inhibition in the uptake of CNDs in macrophages treated with nocodazole (microtubule disruptor), N-phenylanthranilic acid (chloride channel blocker), and mercury chloride (aquaporin channel inhibitor). Collectively, this research provides evidence that CNDs cause functional changes in macrophages and indicates a variety of potential entrance routes. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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16 pages, 4059 KiB

Open AccessArticle

Combining Dextran Conjugates with Stimuli-Responsive and Folate-Targeting Activity: A New Class of Multifunctional Nanoparticles for Cancer Therapy

by Manuela Curcio, Alessandro Paolì, Giuseppe Cirillo, Sebastiano Di Pietro, Martina Forestiero, Francesca Giordano, Loredana Mauro, Diana Amantea, Valeria Di Bussolo, Fiore Pasquale Nicoletta and Francesca Iemma

Nanomaterials 2021, 11(5), 1108; https://doi.org/10.3390/nano11051108 - 25 Apr 2021

Cited by 12 | Viewed by 2213

Abstract

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for [...] Read more.

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for folate receptors were prepared by the combination of two amphiphilic dextran (DEX) derivatives. DEXFA conjugate was obtained by covalent coupling of the polysaccharide with folic acid (FA), whereas DEXssPEGCOOH derived from a reductive amination step of DEX was followed by condensation with polyethylene glycol 600. After self-assembling, nanoparticles with a mean size of 50 nm, able to be destabilized in acidic pH and reducing media, were obtained. Doxorubicin was loaded during the self-assembling process, and the release experiments showed the ability of the proposed system to modulate the drug release in response to different pH and redox conditions. Finally, the viability and uptake experiments on healthy (MCF-10A) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a new drug vector in cancer therapy. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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16 pages, 4667 KiB

Open AccessArticle

Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin Receptor Overexpressed Cancer Cells

by Guan Zhen He and Wen Jen Lin

Nanomaterials 2021, 11(3), 772; https://doi.org/10.3390/nano11030772 - 18 Mar 2021

Cited by 19 | Viewed by 2485

Abstract

Seliciclib, a broad cyclin-dependent kinases (CDKs) inhibitor, exerts its potential role in cancer therapy. For taking advantage of overexpressive transferrin receptor (TfR) on most cancer cells, T7 peptide, a TfR targeting ligand, was selected as a targeting ligand to facilitate nanoparticles (NPs) internalization [...] Read more.

Seliciclib, a broad cyclin-dependent kinases (CDKs) inhibitor, exerts its potential role in cancer therapy. For taking advantage of overexpressive transferrin receptor (TfR) on most cancer cells, T7 peptide, a TfR targeting ligand, was selected as a targeting ligand to facilitate nanoparticles (NPs) internalization in cancer cells. In this study, poly(d,l-lactide-co-glycolide) (PLGA) was conjugated with maleimide poly(ethylene glycol) amine (Mal-PEG-NH₂) to form PLGA-PEG-maleimide copolymer. The synthesized copolymer was used to prepare NPs for encapsulation of seliciclib which was further decorated by T7 peptide. The result shows that the better cellular uptake was achieved by T7 peptide-modified NPs particularly in TfR-high expressed cancer cells in order of MDA-MB-231 breast cancer cells > SKOV-3 ovarian cancer cells > U87-MG glioma cells. Both SKOV-3 and U87-MG cells are more sensitive to encapsulated seliciclib in T7-decorated NPs than to free seliciclib, and that IC₅₀ values were lowered for encapsulated seliciclib. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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17 pages, 2461 KiB

Open AccessArticle

Hadron Therapy, Magnetic Nanoparticles and Hyperthermia: A Promising Combined Tool for Pancreatic Cancer Treatment

by Francesca Brero, Martin Albino, Antonio Antoccia, Paolo Arosio, Matteo Avolio, Francesco Berardinelli, Daniela Bettega, Paola Calzolari, Mario Ciocca, Maurizio Corti, Angelica Facoetti, Salvatore Gallo, Flavia Groppi, Andrea Guerrini, Claudia Innocenti, Cristina Lenardi, Silvia Locarno, Simone Manenti, Renato Marchesini, Manuel Mariani, Francesco Orsini, Emanuele Pignoli, Claudio Sangregorio, Ivan Veronese and Alessandro Lascialfari Show full author list Hide full author list

Nanomaterials 2020, 10(10), 1919; https://doi.org/10.3390/nano10101919 - 25 Sep 2020

Cited by 55 | Viewed by 5620

Abstract

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0–2 Gy for carbon ions and 0–7 Gy for 6 MV photons. Hyperthermia is [...] Read more.

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0–2 Gy for carbon ions and 0–7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/g_Fe3o₄ coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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Review

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38 pages, 2412 KiB

Open AccessReview

Hyaluronic Acid within Self-Assembling Nanoparticles: Endless Possibilities for Targeted Cancer Therapy

by Manuela Curcio, Orazio Vittorio, Jessica Lilian Bell, Francesca Iemma, Fiore Pasquale Nicoletta and Giuseppe Cirillo

Nanomaterials 2022, 12(16), 2851; https://doi.org/10.3390/nano12162851 - 18 Aug 2022

Cited by 8 | Viewed by 2832

Abstract

Self-assembling nanoparticles (SANPs) based on hyaluronic acid (HA) represent unique tools in cancer therapy because they combine the HA targeting activity towards cancer cells with the advantageous features of the self-assembling nanosystems, i.e., chemical versatility and ease of preparation and scalability. This review [...] Read more.

Self-assembling nanoparticles (SANPs) based on hyaluronic acid (HA) represent unique tools in cancer therapy because they combine the HA targeting activity towards cancer cells with the advantageous features of the self-assembling nanosystems, i.e., chemical versatility and ease of preparation and scalability. This review describes the key outcomes arising from the combination of HA and SANPs, focusing on nanomaterials where HA and/or HA-derivatives are inserted within the self-assembling nanostructure. We elucidate the different HA derivatization strategies proposed for this scope, as well as the preparation methods used for the fabrication of the delivery device. After showing the biological results in the employed in vivo and in vitro models, we discussed the pros and cons of each nanosystem, opening a discussion on which approach represents the most promising strategy for further investigation and effective therapeutic protocol development. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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28 pages, 1214 KiB

Open AccessReview

Nanotechnologies in Delivery of DNA and mRNA Vaccines to the Nasal and Pulmonary Mucosa

by Jie Tang, Larry Cai, Chuanfei Xu, Si Sun, Yuheng Liu, Joseph Rosenecker and Shan Guan

Nanomaterials 2022, 12(2), 226; https://doi.org/10.3390/nano12020226 - 11 Jan 2022

Cited by 22 | Viewed by 5663

Abstract

Recent advancements in the field of in vitro transcribed mRNA (IVT-mRNA) vaccination have attracted considerable attention to such vaccination as a cutting-edge technique against infectious diseases including COVID-19 caused by SARS-CoV-2. While numerous pathogens infect the host through the respiratory mucosa, conventional parenterally [...] Read more.

Recent advancements in the field of in vitro transcribed mRNA (IVT-mRNA) vaccination have attracted considerable attention to such vaccination as a cutting-edge technique against infectious diseases including COVID-19 caused by SARS-CoV-2. While numerous pathogens infect the host through the respiratory mucosa, conventional parenterally administered vaccines are unable to induce protective immunity at mucosal surfaces. Mucosal immunization enables the induction of both mucosal and systemic immunity, efficiently removing pathogens from the mucosa before an infection occurs. Although respiratory mucosal vaccination is highly appealing, successful nasal or pulmonary delivery of nucleic acid-based vaccines is challenging because of several physical and biological barriers at the airway mucosal site, such as a variety of protective enzymes and mucociliary clearance, which remove exogenously inhaled substances. Hence, advanced nanotechnologies enabling delivery of DNA and IVT-mRNA to the nasal and pulmonary mucosa are urgently needed. Ideal nanocarriers for nucleic acid vaccines should be able to efficiently load and protect genetic payloads, overcome physical and biological barriers at the airway mucosal site, facilitate transfection in targeted epithelial or antigen-presenting cells, and incorporate adjuvants. In this review, we discuss recent developments in nucleic acid delivery systems that target airway mucosa for vaccination purposes. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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25 pages, 3074 KiB

Open AccessReview

Novel Perspectives towards RNA-Based Nano-Theranostic Approaches for Cancer Management

by Rabia Arshad, Iqra Fatima, Saman Sargazi, Abbas Rahdar, Milad Karamzadeh-Jahromi, Sadanand Pandey, Ana M. Díez-Pascual and Muhammad Bilal

Nanomaterials 2021, 11(12), 3330; https://doi.org/10.3390/nano11123330 - 08 Dec 2021

Cited by 31 | Viewed by 3847

Abstract

In the fight against cancer, early diagnosis is critical for effective treatment. Traditional cancer diagnostic technologies, on the other hand, have limitations that make early detection difficult. Therefore, multi-functionalized nanoparticles (NPs) and nano-biosensors have revolutionized the era of cancer diagnosis and treatment for [...] Read more.

In the fight against cancer, early diagnosis is critical for effective treatment. Traditional cancer diagnostic technologies, on the other hand, have limitations that make early detection difficult. Therefore, multi-functionalized nanoparticles (NPs) and nano-biosensors have revolutionized the era of cancer diagnosis and treatment for targeted action via attaching specified and biocompatible ligands to target the tissues, which are highly over-expressed in certain types of cancers. Advancements in multi-functionalized NPs can be achieved via modifying molecular genetics to develop personalized and targeted treatments based on RNA interference. Modification in RNA therapies utilized small RNA subunits in the form of small interfering RNAs (siRNA) for overexpressing the specific genes of, most commonly, breast, colon, gastric, cervical, and hepatocellular cancer. RNA-conjugated nanomaterials appear to be the gold standard for preventing various malignant tumors through focused diagnosis and delivering to a specific tissue, resulting in cancer cells going into programmed death. The latest advances in RNA nanotechnology applications for cancer diagnosis and treatment are summarized in this review. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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20 pages, 1683 KiB

Open AccessReview

Advances in Nanomaterials Used in Co-Delivery of siRNA and Small Molecule Drugs for Cancer Treatment

by Shei Li Chung, Maxine Swee-Li Yee, Ling-Wei Hii, Wei-Meng Lim, Mui Yen Ho, Poi Sim Khiew and Chee-Onn Leong

Nanomaterials 2021, 11(10), 2467; https://doi.org/10.3390/nano11102467 - 22 Sep 2021

Cited by 12 | Viewed by 3067

Abstract

Recent advancements in nanotechnology have improved our understanding of cancer treatment and allowed the opportunity to develop novel delivery systems for cancer therapy. The biological complexities of cancer and tumour micro-environments have been shown to be highly challenging when treated with a single [...] Read more.

Recent advancements in nanotechnology have improved our understanding of cancer treatment and allowed the opportunity to develop novel delivery systems for cancer therapy. The biological complexities of cancer and tumour micro-environments have been shown to be highly challenging when treated with a single therapeutic approach. Current co-delivery systems which involve delivering small molecule drugs and short-interfering RNA (siRNA) have demonstrated the potential of effective suppression of tumour growth. It is worth noting that a considerable number of studies have demonstrated the synergistic effect of co-delivery systems combining siRNA and small molecule drugs, with promising results when compared to single-drug approaches. This review focuses on the recent advances in co-delivery of siRNA and small molecule drugs. The co-delivery systems are categorized based on the material classes of drug carriers. We discuss the critical properties of materials that enable co-delivery of two distinct anti-tumour agents with different properties. Key examples of co-delivery of drug/siRNA from the recent literature are highlighted and discussed. We summarize the current and emerging issues in this rapidly changing field of research in biomaterials for cancer treatments. Full article

(This article belongs to the Special Issue Nanomaterials for Drug Delivery and Cancer Therapy)

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