scholarly journals Active drug targeting

2020 ◽  
Vol 1 ◽  
Author(s):  
J. Erian ◽  
V. Duerrauer ◽  
L. Rainer ◽  
M. Geppert ◽  
I. A. Joubert ◽  
...  

Over 100 years ago, Paul Ehrlich first proposed the side-chain theory to explain how living cells mount an immune response in reaction to an infection. His theory stated that upon the encounter of a threat, cells express side-chains to bind dangerous toxins. These side-chains,cwhich he later named receptors, can break off the cell and circulate throughout the body (i.e. antibodies). Specific antibodies link to particular antigens in the same way that Emil Fischer proposed enzymes bind to their receptors, “as lock and key”. Ehrlich described these so-called “keys” or antibodies as “magic bullets”, which target toxins without harming the body. In recent years, research has focused on using antibodies not only for detection of infection, but also as aids for drug targeting. Thereby, antibodies are bound to the surface of carriers (e.g. nanoparticles) and facilitate a directed transport to a specific organ or site in the body. Aptamer- peptide- or folic acid-doped carriers furthermore have been shown to specifically target cancer cells. By using hydrophilic structures as carriers (e.g. polyethylene glycol), negative side effects esulting from the accumulation of innate proteins can be prevented. Currently, there are drug carriers in the pre-clinical development phase for the treatment of bowel cancer. Thereby, nano polymer capsules coated with a specific antibody are used to target a glycoprotein expressed on bowel cancer cells. The polymers have a size of approximately 500 nm and are produced with a so-called “layer-by-layer” procedure. Once the carrier has reached its target site, the drug needs to be released in a controlled manner. This can be facilitated, for example, by applying a magnetic field in the case of iron oxide particles. Once these particles are taken up by the cells, magnetic radiation can be used to excite the particles, resulting in the rupture of the cell and subsequent cell death.

1986 ◽  
Vol 15 (4) ◽  
pp. 197-202 ◽  
Author(s):  
E Tomlinson

Site-specific drug carriers are required to exclusively deliver drug molecules to difficult targets within the body. They should do so in a form which protects the drug and host from one another. This contribution reviews the reasons for drug targeting, and describes some of the features required of two types of carrier system, i.e., particulates and soluble (bio)conjugates.


2021 ◽  
Vol 14 (4) ◽  
pp. 1839-1846
Author(s):  
Pradeepa Varadharajaperumal

The use of nanoparticles as drug carriers has been investigated, and it offers various benefits, including the controlled and targeted release of loaded or associated drugs, as well as enhanced drug bioavailability. They do, however, have certain disadvantages, such as in vivo toxicity, which affects all organs, including healthy ones, and overall disease treatment improvement, which might be undetectable or limited. Silver nanoparticles are being studied more and more due to their unique physical, chemical, and optical properties, which allow them to be used in a variety of applications, including drug delivery to specific targets in the body. Given the constraints of traditional cancer treatment, such as low bioavailability and the resulting usage of high doses that produce side effects, attempts to address these challenges are essential. In this work, Biocompatible Silver nanoparticles (AgNps) loaded with tamoxifen have been prepared using the gelation process. Tamoxifen-loaded green synthesized AgNps are reported to be amorphous. The phytochemicals present in the extract of Hemionitis arifolia leaf were responsible for the reduction of silver nitrate to AgNPs. The functional groups existing in the particles were identified with FT-IR analysis. XRD analysis state that the particles were crystalline in nature and arranged in quartzite crystal. Particle size and shape were illustrated from SEM analysis and revealed that the particles were amorphous in nature. UV-visible spectrophotometer showed the band around 440nm which was identified as “surface Plasmon resonance band”. The synthesized AgNps loaded with tamoxifen were significantly effective against Human breast cancer cells. The silver nanoparticle loaded with tamoxifen was found to be inducing apoptotic signals in the selected cells. It inhibits the breast cancer cells even at the lower concentration of AgNPs and TAM-AgNPs. Further apoptotic studies (AO/EtBr and DAPI) reveal that cell death is due to the fragmentation of nuclear material of the treated cells.


2021 ◽  
Vol 8 ◽  
Author(s):  
Maryam Sharifiaghdam ◽  
Elnaz Shaabani ◽  
Zeynab Sharifiaghdam ◽  
Herlinde De Keersmaecker ◽  
Riet De Rycke ◽  
...  

Nanotechnology has made an important contribution to oncology in recent years, especially for drug delivery. While many different nano-delivery systems have been suggested for cancer therapy, selenium nanoparticles (SeNPs) are particularly promising anticancer drug carriers as their core material offers interesting synergistic effects to cancer cells. Se compounds can exert cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis, eventually leading to apoptosis induction in many kinds of cancer cells. Herein, we report on the design and synthesis of novel layer-by-layer Se-based nanocomplexes (LBL-Se-NCs) as carriers of small interfering RNA (siRNA) for combined gene silencing and apoptosis induction in cancer cells. The LBL-Se-NCs were prepared using a straightforward electrostatic assembly of siRNA and chitosan (CS) on the solid core of the SeNP. In this study, we started by investigating the colloidal stability and protection of the complexed siRNA. The results show that CS not only functioned as an anchoring layer for siRNA, but also provided colloidal stability for at least 20 days in different media when CS was applied as a third layer. The release study revealed that siRNA remained better associated with LBL-Se-NCs, with only a release of 35% after 7 days, as compared to CS-NCs with a siRNA release of 100% after 48 h, making the LBL nanocarrier an excellent candidate as an off-the-shelf formulation. When applied to H1299 cells, it was found that they can selectively induce around 32% apoptosis, while significantly less apoptosis (5.6%) was induced in NIH/3T3 normal cells. At the same time, they were capable of efficiently inducing siRNA downregulation (35%) without loss of activity 7 days post-synthesis. We conclude that LBL-Se-NCs are promising siRNA carriers with enhanced stability and with a dual mode of action against cancer cells.


2020 ◽  
Vol 20 (17) ◽  
pp. 2012-2024
Author(s):  
Loveleen Kaur ◽  
Harvinder S. Sohal ◽  
Manvinder Kaur ◽  
Dharambeer S. Malhi ◽  
Sonali Garg

Background: Recently, the application of cancer nanotechnology-based drug delivery to cancer cells has arisen as an important method to resolve multiple molecular, biophysical, and biochemical obstacles, which the body is preparing to resist against the productive implementation of chemotherapeutic medications. Drug delivery technologies focused on nanoparticles, which have resolved some of the drawbacks of conventional chemotherapy as, decreased drug viscosity, chemo-resistance, precise malignity, limited medicative measures with low oral bioactivity. Due to their adjustable size and surface properties, the half-life period of a drug can be increased in the bloodstream. Objective: The aim of the current study is to collect and document the data available on the drug delivery system for anticancer drugs. The present study includes some of the drug carriers like liposomes, carbon dots, micelles, carbon nanotubes, magnetic nanoparticles, etc. Methods: To write this review, an exhaustive literature survey was carried out using relevant work published in various SCI, Scopus, and non-SCI indexed journals. The different search engines used to download the research/ review papers are Google search, PubMed, Science Direct, Google Scholar, Scientific Information Database and Research Gate, etc. Results: Nanotechnology offers better pharmacokinetics, reduces the systematic toxicities related to the chemotherapies and a better route of drug administration. In the analysis, we critically highlight recent studies on carcinoma-fighting nanotechnology. Conclusion: In the present study, different kinds of nano-based drug delivery systems have been discussed along with their characteristic features, the encapsulation of anticancer agents into different types of nanometresized vehicles and their general mechanism.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 947
Author(s):  
Yoel Goldstein ◽  
Katerina Tischenko ◽  
Yifat Brill-Karniely ◽  
Ofra Benny

Uptake of particles by cells involves various natural mechanisms that are essential for their biological functions. The same mechanisms are used in the engulfment of synthetic colloidal drug carriers, while the extent of the uptake affects the biological performance and selectivity. Thus far, little is known regarding the effect of external biomechanical stimuli on the capacity of the cells to uptake nano and micro carriers. This is relevant for anchorage-dependent cells that have detached from surfaces or for cells that travel in the body such as tumor cells, immune cells and various circulating stem cells. In this study, we hypothesize that cellular deformability is a crucial physical effector for the successful execution of the phagocytosis-like uptake in cancer cells. To test this assumption, we develop a well-controlled tunable method to compare the uptake of inert particles by cancer cells in adherent and non-adherent conditions. We introduce a self-designed 3D-printed apparatus, which enables constant stirring while facilitating a floating environment for cell incubation. We reveal a mechanically mediated phagocytosis-like behavior in various cancer cells, that was dramatically enhance in the detached cell state. Our findings emphasize the importance of including proper biomechanical cues to reliably mimic certain physiological scenarios. Beyond that, we offer a cost-effective accessible research tool to study mixed cultures for both adherent and non-adherent cells.


2020 ◽  
Vol 26 (42) ◽  
pp. 5488-5502 ◽  
Author(s):  
Yub Raj Neupane ◽  
Asiya Mahtab ◽  
Lubna Siddiqui ◽  
Archu Singh ◽  
Namrata Gautam ◽  
...  

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.


Author(s):  
Menghan Gao ◽  
Hong Deng ◽  
Weiqi Zhang

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.


Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 462 ◽  
Author(s):  
Joanna Pilch ◽  
Patrycja Kowalik ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
Ewa Augustin

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.


2021 ◽  
Vol 10 (2) ◽  
pp. 228
Author(s):  
Tomonari Kinoshita ◽  
Taichiro Goto

Despite complete resection, cancer recurrence frequently occurs in clinical practice. This indicates that cancer cells had already metastasized from their organ of origin at the time of resection or had circulated throughout the body via the lymphatic and vascular systems. To obtain this potential for metastasis, cancer cells must undergo essential and intrinsic processes that are supported by the tumor microenvironment. Cancer-associated inflammation may be engaged in cancer development, progression, and metastasis. Despite numerous reports detailing the interplays between cancer and its microenvironment via the inflammatory network, the status of cancer-associated inflammation remains difficult to recognize in clinical settings. In the current paper, we reviewed clinical reports on the relevance between inflammation and cancer recurrence after surgical resection, focusing on inflammatory indicators and cancer recurrence predictors according to cancer type and clinical indicators.


2021 ◽  
Vol 8 (7) ◽  
pp. 117
Author(s):  
Giovanni Cilia ◽  
Laura Zavatta ◽  
Rosa Ranalli ◽  
Antonio Nanetti ◽  
Laura Bortolotti

The deformed wing virus (DWV) is one of the most common honey bee pathogens. The virus may also be detected in other insect species, including Bombus terrestris adults from wild and managed colonies. In this study, individuals of all stages, castes, and sexes were sampled from three commercial colonies exhibiting the presence of deformed workers and analysed for the presence of DWV. Adults (deformed individuals, gynes, workers, males) had their head exscinded from the rest of the body and the two parts were analysed separately by RT-PCR. Juvenile stages (pupae, larvae, and eggs) were analysed undissected. All individuals tested positive for replicative DWV, but deformed adults showed a higher number of copies compared to asymptomatic individuals. Moreover, they showed viral infection in their heads. Sequence analysis indicated that the obtained DWV amplicons belonged to a strain isolated in the United Kingdom. Further studies are needed to characterize the specific DWV target organs in the bumblebees. The result of this study indicates the evidence of DWV infection in B. terrestris specimens that could cause wing deformities, suggesting a relationship between the deformities and the virus localization in the head. Further studies are needed to define if a specific organ could be a target in symptomatic bumblebees.


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