Protein-Based Nanoparticles for Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 17570

Special Issue Editor


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Guest Editor
Division of Chemical Engineering and Bioengineering, Kangwon National University, Chuncheon 24341, Korea
Interests: protein nanoparticles; therapeutic protein and antibody production; immune cell therapy; stem cell engineering; CRISPR gene editing; virus; cultured meat

Special Issue Information

Dear Colleagues,

Nanoparticles have been extensively used as carriers for the delivery of chemicals and biomolecular drugs, such as anticancer drugs and therapeutic proteins. Natural biomolecules, such as proteins, are an attractive alternative to synthetic polymers commonly used in nanoparticle formulation because of their safety. In general, protein nanoparticles offer many advantages, such as biocompatibility and biodegradability. Moreover, extracellular vehicles (EVs), such as exosomes, are nano-sized vesicles derived from endocytic membranes and contain biomolecules such as proteins, lipids, RNAs, and DNAs for transfer of signals to recipient cells, playing significant roles in mediating a novel mechanism of cell-to-cell communication. The discovery of exosomes has attracted attention for possible use as next-generation therapies in clinical applications.

The aim of this Special Issue of Pharmaceutics is to collect research and review papers in the range of protein nanoparticles and exosome-related fields for their applications in pharmaceutical areas. We welcome articles dealing with all aspects of protein- and vesicle-based nanodrug delivery systems and invite researchers and drug developers to publish their original research or review articles with expert opinions and perspectives in the area of therapeutics. 

Prof. Hee Ho Park
Guest Editor

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Keywords

  • therapeutic protein production
  • antibody production
  • protein nanoparticles
  • extracellular vesicles
  • exosomes

Published Papers (5 papers)

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Research

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15 pages, 1806 KiB  
Article
Peptide Adjuvant to Invigorate Cytolytic Activity of NK Cells in an Obese Mouse Cancer Model
by Seungmin Han, Minjin Jung, Angela S. Kim, Daniel Y. Lee, Byung-Hyun Cha, Charles W. Putnam, Kwang Suk Lim, David A. Bull and Young-Wook Won
Pharmaceutics 2021, 13(8), 1279; https://doi.org/10.3390/pharmaceutics13081279 - 17 Aug 2021
Viewed by 2011
Abstract
Cancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates glucose metabolism, rendering the tumor microenvironment [...] Read more.
Cancer patients who are overweight compared to those with normal body weight have obesity-associated alterations of natural killer (NK) cells, characterized by poor cytotoxicity, slow proliferation, and inadequate anti-cancer activity. Concomitantly, prohibitin overexpressed by cancer cells elevates glucose metabolism, rendering the tumor microenvironment (TME) more tumor-favorable, and leading to malfunction of immune cells present in the TME. These changes cause vicious cycles of tumor growth. Adoptive immunotherapy has emerged as a promising option for cancer patients; however, obesity-related alterations in the TME allow the tumor to bypass immune surveillance and to down-regulate the activity of adoptively transferred NK cells. We hypothesized that inhibiting the prohibitin signaling pathway in an obese model would reduce glucose metabolism of cancer cells, thereby changing the TME to a pro-immune microenvironment and restoring the cytolytic activity of NK cells. Priming tumor cells with an inhibitory the prohibitin-binding peptide (PBP) enhances cytokine secretion and augments the cytolytic activity of adoptively transferred NK cells. NK cells harvested from the PBP-primed tumors exhibit multiple markers associated with the effector function of active NK cells. Our findings suggest that PBP has the potential as an adjuvant to enhance the cytolytic activity of adoptively transferred NK cells in cancer patients with obesity. Full article
(This article belongs to the Special Issue Protein-Based Nanoparticles for Drug Delivery)
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12 pages, 1763 KiB  
Article
Antioxidative Effects of Carrot-Derived Nanovesicles in Cardiomyoblast and Neuroblastoma Cells
by Do Kyung Kim and Won Jong Rhee
Pharmaceutics 2021, 13(8), 1203; https://doi.org/10.3390/pharmaceutics13081203 - 5 Aug 2021
Cited by 52 | Viewed by 3987
Abstract
Oxidative stress is implicated in many diseases, including cardiovascular and neurodegenerative diseases. Because an increased level of oxidative stress causes apoptosis, it is necessary to inhibit cellular responses to oxidative stress. In this study, Carex, a nanovesicle from carrot, was isolated and investigated [...] Read more.
Oxidative stress is implicated in many diseases, including cardiovascular and neurodegenerative diseases. Because an increased level of oxidative stress causes apoptosis, it is necessary to inhibit cellular responses to oxidative stress. In this study, Carex, a nanovesicle from carrot, was isolated and investigated as a novel biomaterial with antioxidative function in cardiomyoblasts and neuroblastoma cells. A high concentration of nanovesicles was purified from carrots, using size-exclusion chromatography in combination with ultrafiltration. The characterization of Carex demonstrated that it had properties similar to those of extracellular vesicles. Carex showed low cytotoxicity in both H9C2 cardiomyoblasts and SH-SY5Y neuroblastoma cells, when a high level of Carex was delivered to the cells. Carex was further investigated for its antioxidative and apoptotic effects, and it significantly inhibited ROS generation and apoptosis in vitro in myocardial infarction and Parkinson’s disease models. Carex inhibited the reduction of antioxidative molecule expression, including Nrf-2, HO-1, and NQO-1, in both models. Considering its antioxidative function and high production yield, Carex is a potential drug candidate for the treatment of myocardial infarction as well as Parkinson’s disease. Thus, the results demonstrated in this study will contribute to an exploration of a novel drug, using nanovesicles from plants, including carrots. Full article
(This article belongs to the Special Issue Protein-Based Nanoparticles for Drug Delivery)
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18 pages, 5376 KiB  
Article
A Quantitative Pharmacology Model of Exosome-Mediated Drug Efflux and Perturbation-Induced Synergy
by Jin Wang, Bertrand Z. Yeung, M. Guillaume Wientjes, Minjian Cui, Cody J. Peer, Ze Lu, William D. Figg, Sukyung Woo and Jessie L.-S. Au
Pharmaceutics 2021, 13(7), 997; https://doi.org/10.3390/pharmaceutics13070997 - 30 Jun 2021
Cited by 5 | Viewed by 2598
Abstract
Exosomes, naturally occurring vesicles secreted by cells, are undergoing development as drug carriers. We used experimental and computational studies to investigate the kinetics of intracellular exosome processing and exosome-mediated drug efflux and the effects of exosome inhibition. The experiments used four human-breast or [...] Read more.
Exosomes, naturally occurring vesicles secreted by cells, are undergoing development as drug carriers. We used experimental and computational studies to investigate the kinetics of intracellular exosome processing and exosome-mediated drug efflux and the effects of exosome inhibition. The experiments used four human-breast or ovarian cancer cells, a cytotoxic drug paclitaxel (PTX), two exosome inhibitors (omeprazole (OME), which inhibits exosome release, and GW4869 (GW), which inhibits synthesis of sphingolipid ceramide required for exosome formation), LC-MS/MS analysis of PTX levels in exosomes, and confocal microscopic study of endocytic transport (monitored using fluorescent nanoparticles and endocytic organelle markers). In all four cells, exosome production was enhanced by PTX but diminished by OME or GW (p < 0.05); the PTX enhancement was completely reversed by OME or GW. Co-treatment with OME or GW simultaneously reduced PTX amount in exosomes and increased PTX amount and cytotoxicity in exosome-donor cells (corresponding to >2-fold synergy as indicated by curve shift and uncertainty envelope analyses). This synergy is consistent with the previous reports that OME co-administration significantly enhances the taxane activity in tumor-bearing mice and in patients with triple negative metastatic breast cancer. The experimental results were used to develop a quantitative pharmacology model; model simulations revealed the different effects of the two exosome inhibitors on intracellular PTX processing and subcellular distribution. Full article
(This article belongs to the Special Issue Protein-Based Nanoparticles for Drug Delivery)
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9 pages, 1439 KiB  
Article
Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis
by Amin Mirzaaghasi, Yunho Han, So-Hee Ahn, Chulhee Choi and Ji-Ho Park
Pharmaceutics 2021, 13(3), 427; https://doi.org/10.3390/pharmaceutics13030427 - 22 Mar 2021
Cited by 28 | Viewed by 4987
Abstract
Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to [...] Read more.
Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors. Full article
(This article belongs to the Special Issue Protein-Based Nanoparticles for Drug Delivery)
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Review

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21 pages, 3254 KiB  
Review
Engineering Therapeutic Strategies in Cancer Immunotherapy via Exogenous Delivery of Toll-like Receptor Agonists
by Sehwan Jeong, Yunyoung Choi and Kyobum Kim
Pharmaceutics 2021, 13(9), 1374; https://doi.org/10.3390/pharmaceutics13091374 - 31 Aug 2021
Cited by 14 | Viewed by 3005
Abstract
As a currently spotlighted method for cancer treatment, cancer immunotherapy has made a lot of progress in recent years. Among tremendous cancer immunotherapy boosters available nowadays, Toll-like receptor (TLR) agonists were specifically selected, because of their effective activation of innate and adaptive immune [...] Read more.
As a currently spotlighted method for cancer treatment, cancer immunotherapy has made a lot of progress in recent years. Among tremendous cancer immunotherapy boosters available nowadays, Toll-like receptor (TLR) agonists were specifically selected, because of their effective activation of innate and adaptive immune cells, such as dendritic cells (DCs), T cells, and macrophages. TLR agonists can activate signaling pathways of DCs to express CD80 and CD86 molecules, and secrete various cytokines and chemokines. The maturation of DCs stimulates naïve T cells to differentiate into functional cells, and induces B cell activation. Although TLR agonists have anti-tumor ability by activating the immune system of the host, their drawbacks, which include poor efficiency and remarkably short retention time in the body, must be overcome. In this review, we classify and summarize the recently reported delivery strategies using (1) exogenous TLR agonists to maintain the biological and physiological signaling activities of cargo agonists, (2) usage of multiple TLR agonists for synergistic immune responses, and (3) co-delivery using the combination with other immunomodulators or stimulants. In contrast to naked TLR agonists, these exogenous TLR delivery strategies successfully facilitated immune responses and subsequently mediated anti-tumor efficacy. Full article
(This article belongs to the Special Issue Protein-Based Nanoparticles for Drug Delivery)
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