Nanoparticle Delivery: Targeting and Nonspecific Binding

AbstractTargeted cancer therapies focus on molecular and cellular changes that are specific to cancer and hold the promise of harming fewer normal cells, reducing side effects, and improving the quality of life. One major challenge in cancer nanotechnology is how to selectively deliver nanoparticles to diseased tissues while simultaneously minimizing the accumulation onto the nanoparticle of unwanted materials (e.g., proteins in the blood) during the delivery process. Once therapeutic nanoparticles have been created, very often they are linked or coated to other molecules that assist in targeting the delivery of nanoparticles to different cell types of the body. These linkers or coatings have been termed targeting ligands or “smart molecules” because of their inherent ability to direct selective binding to cell types or states and, therefore, confer “smartness” to nanoparticles. Likewise, “smartness” can be imparted to the nanoparticles to selectively repel unwanted entities in the body. To date, such smart molecules can consist of peptides, antibodies, engineered proteins, nucleic acid aptamers, or small organic molecules. This review describes how such smart molecules are discovered, enhanced, and anchored to nanoparticles, with an emphasis on how to minimize nonspecific interactions of nanoparticles to unintended targets.

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Role of POT1 in Human Cancer

Cancers ◽

10.3390/cancers12102739 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2739 ◽

Cited By ~ 2

Author(s):

Yangxiu Wu ◽

Rebecca C. Poulos ◽

Roger R. Reddel

Keyword(s):

Human Cancer ◽

Cell Types ◽

Cancer Therapies ◽

Telomeric Dna ◽

Targeted Cancer Therapies ◽

Length Regulation ◽

Tumor Types ◽

Different Cell Types ◽

Essential Subunit

Telomere abnormalities facilitate cancer development by contributing to genomic instability and cellular immortalization. The Protection of Telomeres 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex. It directly binds to single-stranded telomeric DNA, protecting chromosomal ends from an inappropriate DNA damage response, and plays a role in telomere length regulation. Alterations of POT1 have been detected in a range of cancers. Here, we review the biological functions of POT1, the prevalence of POT1 germline and somatic mutations across cancer predisposition syndromes and tumor types, and the dysregulation of POT1 expression in cancers. We propose a framework for understanding how POT1 abnormalities may contribute to oncogenesis in different cell types. Finally, we summarize the clinical implications of POT1 alterations in the germline and in cancer, and possible approaches for the development of targeted cancer therapies.

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Cryo-Electron Microscopy Structure and Interactions of the Human Cytomegalovirus gHgLgO Trimer with Platelet-Derived Growth Factor Receptor Alpha

mBio ◽

10.1128/mbio.02625-21 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Jing Liu ◽

Adam Vanarsdall ◽

Dong-Hua Chen ◽

Andrea Chin ◽

David Johnson ◽

...

Keyword(s):

Birth Defects ◽

Adult Population ◽

Growth Factor Receptor ◽

Cell Types ◽

The Body ◽

Platelet Derived Growth Factor ◽

Cryo Electron Microscopy ◽

Factor Receptor Alpha ◽

Complex Protein ◽

Different Cell Types

HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits.

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Infection and immunity

Oxford Handbook of Medical Sciences ◽

10.1093/med/9780198789895.003.0012 ◽

2021 ◽

pp. 853-920

Keyword(s):

Major Histocompatibility Complex ◽

Immune System ◽

Cell Types ◽

The Body ◽

Acquired Immunity ◽

Histocompatibility Complex ◽

Repair Mechanisms ◽

Antigen Presenting ◽

Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

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Analysis of oral complications related to cancer therapy

Archives of Oral Research ◽

10.7213/archivesoforalresearch.09.002.ao02 ◽

2013 ◽

Vol 9 (2) ◽

Author(s):

Antonio Eugenio Magnabosco Neto ◽

Fernando Henrique Westphalen

Keyword(s):

Oral Cavity ◽

Cancer Treatment ◽

Medical Records ◽

Adverse Reactions ◽

The Body ◽

Cancer Therapies ◽

Oral Complications ◽

Dose Limitation ◽

Number Of Patients

Introduction: The side effects and adverse reactions related to cancer therapies may cause significant alterations in the oral cavity, discomfort or even severe pain in parts of the body, patient’s nutritional deficiency, delay in the administration of oncologic drugs or dose limitation, an increase of hospitalization time and of the related expenses, as well as a decrease in the patient’s quality of life. Objective: The purpose of this study was to determine the deleterious effects of cancer therapies in the oral cavity. Material and methods: Data was gathered from medical records of the treatment of 643 cancer patients at the São José Hospital, in Joinville, state of Santa Catarina, from January to September 2012. Among the records selected for this study, 59.41% were female patients, with a mean age of 51 to 60 years. Results: Oral complications were reported in 72.47% of the patients, and the complication with the highest prevalence was mucositis (14.62%) followed by dry mouth (10.58%). Most of the patients had not received dental care prior to the cancer treatment, and no dental record was found. Conclusions: Several different oral disorders were reported as a result of cancer treatment, and a significant number of patients needed dental evaluation prior to the treatment.

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Adiponectin: a pleiotropic hormone with multifaceted roles

Problems of Endocrinology ◽

10.14341/probl12827 ◽

2021 ◽

Vol 67 (6) ◽

pp. 98-112

Author(s):

S. S. Shklyaev ◽

G. A. Melnichenko ◽

N. N. Volevodz ◽

N. A. Falaleeva ◽

S. A. Ivanov ◽

...

Keyword(s):

Cell Types ◽

The Body ◽

Biologically Active ◽

Protective Effects ◽

Immune Functions ◽

Ample Evidence ◽

Endocrine Organs ◽

Different Types ◽

Different Cell Types ◽

Pleiotropic Actions

Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called ‘adiponectin paradox’. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

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Responses and coping methods of different testicular cell types to heat stress: overview and perspectives

Bioscience Reports ◽

10.1042/bsr20210443 ◽

2021 ◽

Author(s):

Hui Cai ◽

Dezhe Qin ◽

Sha Peng

Keyword(s):

Heat Stress ◽

Leydig Cells ◽

Cell Types ◽

Cellular Responses ◽

Body Cavity ◽

The Body ◽

Testicular Cell ◽

Coping Methods ◽

And Coping ◽

Different Cell Types

To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells, spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat-stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.

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Immunological changes accompanying the development of experimental neoplastic process

Pediatrician (St Petersburg) ◽

10.17816/ped6296-108 ◽

2015 ◽

Vol 6 (2) ◽

pp. 96-108

Author(s):

Elena Aleksandrovna Dementeva ◽

Olga Petrovna Gurina

Keyword(s):

Immune Response ◽

Immune System ◽

Genome Stability ◽

Cell Types ◽

Transformation Process ◽

The Body ◽

Expression Of Genes ◽

Neoplastic Process ◽

And Control ◽

Different Cell Types

The key immunology problem remains the understanding of the mechanisms for the effective protection of the body against various pathogens with simultaneous suppression of the immune response to autoantigens. The pathogenesis of neoplastic pathological processes includes violations of the mechanisms of normal cell growth and cell proliferation. Antitumor immune response is a complex event, involving many different cell types. But despite the ability of the immune system to recognize and respond to a variety of tumor-associated antigens, the neoplastic process overcomes the protective forces of the organism, grows and spreads. For cancer cells characterized by independence from antiproliferative signals, autocrine stimulation of growth disturbances in the system, induction of apoptosis and control of genome stability. As a result of accumulation of genetic and epigenetic changes in tumor cells differ significantly from the normal range and the level of expression of genes involved in the transformation process, the accumulation of mutations in key genes promoters and suppressors of tumorigenesis. This creates the opportunity for recognition by cells of the immune system. The study of changes in value and operation of the various elements of the immune system in the development of experimental neoplastic process allows you to identify the mechanisms of interaction in the system «malignant tumor-immune system, to assess patterns of interaction with other organs and tissues, to create a theoretical pathogenetically reasonable premise for the development of anticancer therapy.

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The Tuberculous Granuloma: An Unsuccessful Host Defence Mechanism Providing a Safety Shelter for the Bacteria?

Clinical and Developmental Immunology ◽

10.1155/2012/139127 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 97

Author(s):

Mayra Silva Miranda ◽

Adrien Breiman ◽

Sophie Allain ◽

Florence Deknuydt ◽

Frederic Altare

Keyword(s):

Cell Types ◽

Giant Cells ◽

The Body ◽

Differentiated Cells ◽

Latently Infected ◽

Long Time ◽

Infectious Stage ◽

Different Cell Types

One of the main features of the immune response toM. Tuberculosisis the formation of an organized structure called granuloma. It consists mainly in the recruitment at the infectious stage of macrophages, highly differentiated cells such as multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded by a rim of lymphocytes. Although in the first instance the granuloma acts to constrain the infection, some bacilli can actually survive inside these structures for a long time in a dormant state. For some reasons, which are still unclear, the bacilli will reactivate in 10% of the latently infected individuals, escape the granuloma and spread throughout the body, thus giving rise to clinical disease, and are finally disseminated throughout the environment. In this review we examine the process leading to the formation of the granulomatous structures and the different cell types that have been shown to be part of this inflammatory reaction. We also discuss the differentin vivoandin vitromodels available to study this fascinating immune structure.

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Molecular Aspects of Regeneration Mechanisms in Holothurians

Genes ◽

10.3390/genes12020250 ◽

2021 ◽

Vol 12 (2) ◽

pp. 250 ◽

Cited By ~ 1

Author(s):

Igor Yu. Dolmatov

Keyword(s):

Spatial Organization ◽

Molecular Mechanisms ◽

Cell Types ◽

Molecular Data ◽

The Body ◽

Matrix Remodeling ◽

Oxygen Species ◽

Morphological And Molecular Data ◽

Molecular Aspects ◽

Different Cell Types

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation).

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The Effect of Collagen-I Coatings of 3D Printed PCL Scaffolds for Bone Replacement on Three Different Cell Types

Applied Sciences ◽

10.3390/app112211063 ◽

2021 ◽

Vol 11 (22) ◽

pp. 11063

Author(s):

Lucas Weingärtner ◽

Sergio H. Latorre ◽

Dirk Velten ◽

Anke Bernstein ◽

Hagen Schmal ◽

...

Keyword(s):

Tissue Engineering ◽

Type I Collagen ◽

Testing Machine ◽

Cell Types ◽

The Body ◽

Type I ◽

Human Tissues ◽

Cytotoxicity Studies ◽

Cell Scaffold ◽

Different Cell Types

Introduction The use of scaffolds in tissue engineering is becoming increasingly important as solutions need to be found to preserve human tissues such as bone or cartilage. Various factors, including cells, biomaterials, cell and tissue culture conditions, play a crucial role in tissue engineering. The in vivo environment of the cells exerts complex stimuli on the cells, thereby directly influencing cell behavior, including proliferation and differentiation. Therefore, to create suitable replacement or regeneration procedures for human tissues, the conditions of the cells’ natural environment should be well mimicked. Therefore, current research is trying to develop 3-dimensional scaffolds (scaffolds) that can elicit appropriate cellular responses and thus help the body regenerate or replace tissues. In this work, scaffolds were printed from the biomaterial polycaprolactone (PCL) on a 3D bioplotter. Biocompatibility testing was used to determine whether the printed scaffolds were suitable for use in tissue engineering. Material and Methods An Envisiontec 3D bioplotter was used to fabricate the scaffolds. For better cell-scaffold interaction, the printed polycaprolactone scaffolds were coated with type-I collagen. Three different cell types were then cultured on the scaffolds and various tests were used to investigate the biocompatibility of the scaffolds. Results Reproducible scaffolds could be printed from polycaprolactone. In addition, a coating process with collagen was developed, which significantly improved the cell-scaffold interaction. Biocompatibility tests showed that the PCL-collagen scaffolds are suitable for use with cells. The cells adhered to the surface of the scaffolds and as a result extensive cell growth was observed on the scaffolds. The inner part of the scaffolds, however, remained largely uninhabited. In the cytotoxicity studies, it was found that toxicity below 20% was present in some experimental runs. The determination of the compressive strength by means of the universal testing machine Z005 by ZWICK according to DIN EN ISO 604 of the scaffolds resulted in a value of 68.49 ± 0.47 MPa.

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