From Passive Targeting to Personalized Nanomedicine: Multidimensional Insights on Nanoparticles’ Interaction with the Tumor Microenvironment

2020 ◽  
Vol 21 ◽  
Author(s):  
Aya A. Sebak ◽  
Basma M. El-Shenawy ◽  
Sara El-Safy ◽  
Mohamed El-Shazly
Keyword(s):  
Tumor Microenvironment ◽  
Protein Corona ◽  
Lymphatic Drainage ◽  
Biological Macromolecules ◽  
Passive Targeting ◽  
Epr Effect ◽  
The Past ◽  
Current Trends ◽  
Enhanced Permeability And Retention ◽  
Therapeutic Outcomes

: Nanomedicine is revolutionizing the treatment of cancer and has achieved unprecedented outcomes over the past decades. The accumulation of nanoparticles (NPs) in different tumors relies mainly on the enhanced permeability and retention (EPR) effect benefiting from the wide fenestrae of the tumor vasculature and the lack of lymphatic drainage. However, the EPR effect is recognized as a heterogeneous phenomenon resulting in heterogeneous outcomes of clinical trials. Extensive efforts are exerted to enhance the outcomes of nanomedicine in a larger cohort of patients by employing active targeting strategies. However, actively targeted NPs accumulate in tumors by the EPR effect and hence fail to achieve convincing therapeutic outcomes. These obstacles are gradually being removed by improving the understanding of the tumor microenvironment (TME) and the mechanistic interaction of the NPs with its different components. In this review, we provide detailed insights into the past concerns of drug targeting, the current trends of TME reengineering, and the future implications for overcoming past hurdles. Strategies explored in this regard included the use of companion diagnostics and the modulation of the protein corona associated with the systemic administration of NPs and their interaction with biological macromolecules.

scholarly journals Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiaoliang Cheng ◽  
Houli Li ◽  
Xuemei Ge ◽  
Lijuan Chen ◽  
Yao Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Academic Research ◽  
Deep Penetration ◽  
Acidic Ph ◽  
Passive Targeting ◽  
Enhanced Permeability And Retention ◽  
Influence Diffusion ◽  
Cancer Diseases ◽  
Ultrasmall Particles

Over the years, the manipulation and clinical application of drug-delivery nanosystems for cancer diseases have attracted a rapid growth of academic research interests, and some nanodrugs have been approved for clinic application. Although encouraging achievements have been made, the potency of nanomedicines in cancer treatment is far from satisfaction, and one significant reason is the inefficient penetration of nanoparticles into solid tumors. Particle size is one of the most significant features that influence diffusion ability of the drug-delivery system in tumors. Size-shrinkable drug-delivery nanosystems possess a size-switchable property that can achieve passive targeting via the enhanced permeability and retention (EPR) effect and transform into ultrasmall particles in tumors for deep penetration into tumors. The tumor microenvironment is characterized by acidic pH, hypoxia, upregulated levels of enzymes, and a redox environment. In this review, we summarize and analyze the current research progresses and challenges in tumor microenvironment responsive size-shrinkable drug-delivery nanosystems. We further expect to present some meaningful proposals and enlightenments on promoting deep penetration into tumors of nanoparticles.

Passive Targeting and the Enhanced Permeability and Retention (EPR) Effect

2021 ◽  
pp. 1-13
Author(s):  
Giovana Onzi ◽  
Silvia S. Guterres ◽  
Adriana R. Pohlmann ◽  
Luiza Abrahão Frank
Keyword(s):  
Passive Targeting ◽  
Epr Effect ◽  
Enhanced Permeability And Retention

Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma

2020 ◽  
Vol 15 (7) ◽  
pp. 588-596
Author(s):  
Haibao Zhang ◽  
Guodong Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Formation ◽  
Biological Behavior ◽  
Tumor Stem Cell ◽  
The Past ◽  
The Common

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

“Economics in Command?” Ideology and Policy Since the Third Plenum, 1978–1984

1984 ◽  
Vol 99 ◽  
pp. 417-461 ◽  
Author(s):  
Stuart R. Schram
Keyword(s):  
Policy Making ◽  
Question Mark ◽  
The Third ◽  
The Past ◽  
Great Leap ◽  
Current Trends

In this article, I shall attempt to give an overview of the most important political and ideological developments during the past six years, and in this context, to assess current trends in China. The three-word title is, of course, deliberately modelled on the Great Leap slogan “Politics in command”, and is intended to evoke the problem of whether or not policy-making since 1978 has been largely shaged by economic realities, and/or by the economic goals of the, leadership I have placed a question mark after it because, though I shall certainly express some opinions on this topic before I have done, I doubt that the issue can as yet be regarded as finally settled.

scholarly journals Current Trends in Dental Composites

1995 ◽  
Vol 6 (4) ◽  
pp. 302-318 ◽  
Author(s):  
J.L. Ferracane
Keyword(s):  
Wear Resistance ◽  
Clinical Performance ◽  
Color Stability ◽  
Dental Composites ◽  
Filler Materials ◽  
Posterior Teeth ◽  
The Past ◽  
Current Trends ◽  
Dentin Adhesives ◽  
High Concentrations

The clinical performance of dental composites has been significantly improved over the past decade through modifications in formulation that include: using more stable polymerization promoters for greater color stability; incorporating high concentrations of finely ground fillers to produce adequate strength and excellent wear resistance while retaining translucency ; adding radiopacifying agents for improved diagnostics; and utilizing dentin adhesives. However, there are problems which limit the use of composites, especially in posterior teeth. The materials remain very technique-sensitive, due to the extensive contraction which accompanies polymerization and negatively influences marginal sealing. In addition, the materials are generally considered to have inadequate mechanical properties and wear resistance in contact areas to serve as total replacements for amalgams. Current efforts are focusing on several areas, including the development of non- or minimally-shrinking dental composites containing spiro-orthocarbonates as additives to dimethacrylates or epoxy-base resins, and the production of alternative filler materials for ideal wear resistance and esthetics. This paper reviews the composition and characteristics of current dental composites, as well as recent areas of study.

scholarly journals Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Dong Huang ◽  
Lingna Sun ◽  
Leaf Huang ◽  
Yanzuo Chen
Keyword(s):  
Blood Vessels ◽  
Tumor Vessels ◽  
Epr Effect ◽  
Nanodrug Delivery ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Long Time ◽  
Vessel Network ◽  
Tumor Blood Vessels ◽  
The Relationship

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

scholarly journals Water confined in solutions of biological relevance

2020 ◽  
Vol 92 (10) ◽  
pp. 1563-1574
Author(s):  
Marie-Claire Bellissent-Funel
Keyword(s):  
Aqueous Solutions ◽  
Bulk Water ◽  
Biological Macromolecules ◽  
Organic Solutes ◽  
Confined Water ◽  
The Past ◽  
Structure And Dynamics ◽  
Biological Relevance ◽  
The Stability

AbstractIn many relevant situations, water is not in its bulk form but instead attached to some substrates or filling some cavities. We shall call water in the latter environment confined water as opposed to bulk water. It is known that the confined water is essential for the stability and the function of biological macromolecules. In this paper, we provide a review of the experimental and computational advances over the past decades concerning the understanding of the structure and dynamics of water confined in aqueous solutions of biological relevance. Examples involving water in solution of organic solutes (cryoprotectants such as dimethylsulfoxide (DMSO), sugars such as trehalose) are provided.

scholarly journals Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1151
Author(s):  
Lu Tang ◽  
Jing Li ◽  
Qingqing Zhao ◽  
Ting Pan ◽  
Hui Zhong ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Treatment ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Targeted Drug Delivery ◽  
Treatment Modalities ◽  
Biological Macromolecules ◽  
Passive Targeting ◽  
Efficient Delivery ◽  
Targeted Drug

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

scholarly journals Fluorescent Chemosensors for Ion and Molecule Recognition: The Next Chapter

2021 ◽  
Vol 2 ◽  
Author(s):  
Kai-Cheng Yan ◽  
Axel Steinbrueck ◽  
Adam C. Sedgwick ◽  
Tony D. James
Keyword(s):  
State Of The Art ◽  
Fluorescent Chemosensors ◽  
Distant Future ◽  
The Past ◽  
Current Trends ◽  
Current State ◽  
Future Challenges ◽  
Molecule Recognition

Over the past 30 years fluorescent chemosensors have evolved to incorporate many optical-based modalities and strategies. In this perspective we seek to highlight the current state of the art as well as provide our viewpoint on the most significant future challenges remaining in the area. To underscore current trends in the field and to facilitate understanding of the area, we provide the reader with appropriate contemporary examples. We then conclude with our thoughts on the most probable directions that chemosensor development will take in the not-too-distant future.

scholarly journals The critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

2020 ◽  
Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Biological Macromolecules

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

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