Extracellular Vesicles, Nanoparticles and Development of Anti-cancer Therapeutics

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 8270

Special Issue Editors


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Guest Editor
Department of Anatomy and Cell Biology, College of Medicine, Gachon University, Incheon, Republic of Korea
Interests: cancer; regenerative medicine; mesenchymal stem cells; extracellular vesicles; angiogenesis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Anatomy and Cell Biology, College of Medicine, Gachon University, Incheon, Korea
Interests: nanomedicine; mesenchymal stem cells; nanoparticles; extracellular vesicles; therapeutics

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs), including exosomes and microvesicles, are membrane-enclosed particles that contain molecular content that is excreted from cells in both normal or diseased states, and they can modulate downstream targets. Isolated molecular content within EVs may provide insight into the state of cells. The combination of nanobiotechnology and extracellular vesicles (EVs) offers a dual opportunity for the development of novel therapeutics against cancer. In the last few decades, combinatorial approaches with nanoparticles have been a popular and effective method of treating cancers of almost every origin. Due to reluctant behavior of nanoparticles along with their low systemic toxicity, higher therapeutic efficacy, greater safety and biocompatibility, increased solubility, higher stability and faster delivery, such nanoparticles and EVs are attractive targets in the field of nanomedicine.

However, EVs have been largely acknowledged as intercellular messengers, allowing the exchange of lipids, proteins, and metabolites between secretory and target cells which trigger various cellular responses. Considering the established side effects of commercially available anti-cancerous drugs, nanoparticles and EVs can be passably absorbed by epithelial cells and immune cells, thereby averting the degradation of binding drugs and improving the pharmacokinetics and distribution characteristics. Moreover, such a combination also reduces the side effects of cytotoxic drugs and improves the curative effect of therapeutic drugs, enhancing tumor penetration, thus providing excellent tumor-targeting effects.

Most nanotherapeutics are often associated with poor efficacy due to the higher rate of clearance by the reticuloendothelial system, short half-lives, non-specific entrapment approaches, and endo-lysosomal mediated degradations. Alongside the technological development in the last decade, researchers have utilized several biologics, including EVs and non-biologics, which encompass organic, inorganic, and hybrid delivery systems that can be used to overcome such challenges.

This Special Issue welcomes both original papers and review articles addressing recent research and novel developments in the field of nanotherapeutics using EVs as biologics for cancer therapy, including in vitro, pre-clinical and clinical applications.

Prof. Dr. Goo-Bo Jeong
Prof. Dr. Alok Raghav
Guest Editors

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Keywords

  • cancer
  • extracellular vesicles
  • nanoparticles
  • drug delivery
  • engineered nanoparticles

Published Papers (4 papers)

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Research

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24 pages, 6426 KiB  
Article
New SDS-Based Polyelectrolyte Multicore Nanocarriers for Paclitaxel Delivery—Synthesis, Characterization, and Activity against Breast Cancer Cells
by Marzena Szwed, Sylwia Michlewska, Katarzyna Kania, Marta Szczęch, Agnieszka Marczak and Krzysztof Szczepanowicz
Cells 2023, 12(16), 2052; https://doi.org/10.3390/cells12162052 - 11 Aug 2023
Viewed by 1145
Abstract
The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main [...] Read more.
The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main objective was to verify the antitumor properties of PTX-loaded NCs and to examine whether the drug encapsulated in these NCs retained its cytotoxic properties. The cytotoxicity of the prepared nanosystems was tested on MCF-7 and MDA-MB-231 tumour cells and the non-cancerous HMEC-1 cell line in vitro. Confocal microscopy, spectrophotometry, spectrofluorimetry, flow cytometry, and RT PCR techniques were used to define the typical hallmarks of apoptosis. It was demonstrated that PTX encapsulated in the tested NCs exhibited similar cytotoxicity to the free drug, especially in the triple negative breast cancer model. Moreover, SDS/PLL/PTX and SDS/PLL/PGA/PTX significantly reduced DNA synthesis. In addition, PTX-loaded NCs triggered apoptosis and upregulated the transcription of Bax, AIF, cytochrome-c, and caspase-3 mRNA. Our data demonstrate that these novel polyelectrolyte multicore NCs coated with PLL or PLL/PGA are good candidates for delivering PTX. Our discoveries have prominent implications for the possible choice of newly synthesized, SDS-based polyelectrolyte multicore NCs in different anticancer therapeutic applications. Full article
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Review

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16 pages, 2334 KiB  
Review
Nanoquercetin and Extracellular Vesicles as Potential Anticancer Therapeutics in Hepatocellular Carcinoma
by Alok Raghav and Goo Bo Jeong
Cells 2024, 13(7), 638; https://doi.org/10.3390/cells13070638 - 05 Apr 2024
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Abstract
Despite world-class sophisticated technologies, robotics, artificial intelligence, and machine learning approaches, cancer-associated mortalities and morbidities have shown continuous increments posing a healthcare burden. Drug-based interventions were associated with systemic toxicities and several limitations. Natural bioactive compounds derived nanoformulations, especially nanoquercetin (nQ), are alternative [...] Read more.
Despite world-class sophisticated technologies, robotics, artificial intelligence, and machine learning approaches, cancer-associated mortalities and morbidities have shown continuous increments posing a healthcare burden. Drug-based interventions were associated with systemic toxicities and several limitations. Natural bioactive compounds derived nanoformulations, especially nanoquercetin (nQ), are alternative options to overcome drug-associated limitations. Moreover, the EVs-based cargo targeted delivery of nQ can have enormous potential in treating hepatocellular carcinoma (HCC). EVs-based nQ delivery synergistically regulates and dysregulates several pathways, including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin, and PI3K/AKT, along with PBX3/ERK1/2/CDK2, and miRNAs intonation. Furthermore, discoveries on possible checkpoints of anticancer signaling pathways were studied, which might lead to the development of modified EVs infused with nQ for the development of innovative treatments for HCC. In this work, we abridged the control of such signaling systems using a synergetic strategy with EVs and nQ. The governing roles of extracellular vesicles controlling the expression of miRNAs were investigated, particularly in relation to HCC. Full article
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24 pages, 1896 KiB  
Review
Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation
by Stavros P. Papadakos, Nikolaos Machairas, Ioanna E. Stergiou, Konstantinos Arvanitakis, Georgios Germanidis, Adam Enver Frampton and Stamatios Theocharis
Cells 2023, 12(16), 2036; https://doi.org/10.3390/cells12162036 - 10 Aug 2023
Cited by 3 | Viewed by 1892
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate and limited treatment options. Recent research has brought attention to the significant importance of intercellular communication in the progression of HCC, wherein exosomes have been identified as critical agents facilitating [...] Read more.
Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate and limited treatment options. Recent research has brought attention to the significant importance of intercellular communication in the progression of HCC, wherein exosomes have been identified as critical agents facilitating cell-to-cell signaling. In this article, we investigate the impact of macrophages as both sources and targets of exosomes in HCC, shedding light on the intricate interplay between exosome-mediated communication and macrophage involvement in HCC pathogenesis. It investigates how exosomes derived from HCC cells and other cell types within the tumor microenvironment (TME) can influence macrophage behavior, polarization, and recruitment. Furthermore, the section explores the reciprocal interactions between macrophage-derived exosomes and HCC cells, stromal cells, and other immune cells, elucidating their role in tumor growth, angiogenesis, metastasis, and immune evasion. The findings presented here contribute to a better understanding of the role of macrophage-derived exosomes in HCC progression and offer new avenues for targeted interventions and improved patient outcomes. Full article
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23 pages, 3171 KiB  
Review
Current Strategies for Exosome Cargo Loading and Targeting Delivery
by Haifeng Zeng, Shaoshen Guo, Xuancheng Ren, Zhenkun Wu, Shuwen Liu and Xingang Yao
Cells 2023, 12(10), 1416; https://doi.org/10.3390/cells12101416 - 17 May 2023
Cited by 28 | Viewed by 4061
Abstract
Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, [...] Read more.
Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes. Full article
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