Penetrating the cell membrane, thermal targeting and novel anticancer drugs: the development of thermally targeted, elastin-like polypeptide cancer therapeutics

Abstract2’3’-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral Stimulator of Interferon Genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.

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Application of Three-dimensional (3D) Tumor Cell Culture Systems and Mechanism of Drug Resistance

Current Pharmaceutical Design ◽

10.2174/1381612825666191014163923 ◽

2019 ◽

Vol 25 (34) ◽

pp. 3599-3607 ◽

Cited By ~ 3

Author(s):

Adeeb Shehzad ◽

Vijaya Ravinayagam ◽

Hamad AlRumaih ◽

Meneerah Aljafary ◽

Dana Almohazey ◽

...

Keyword(s):

Cell Culture ◽

Cancer Cells ◽

Anticancer Drugs ◽

Three Dimensional ◽

3D Culture ◽

3D Cell Culture ◽

Cancer Therapeutics ◽

In Vivo Model

: The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.

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β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007798117 ◽

2020 ◽

Vol 117 (49) ◽

pp. 30942-30948

Author(s):

Wenzhuo Chen ◽

Xuefeng Li ◽

Chengfei Liu ◽

Jia He ◽

Miao Qi ◽

...

Keyword(s):

Drug Delivery ◽

Liver Cancer ◽

Anticancer Drugs ◽

Liver Tumor ◽

Molecular Design ◽

Aqueous Media ◽

Cancer Therapeutics ◽

Critical Aggregation Concentration ◽

Specific Stimulus

Despite the widespread clinical application of chemotherapeutic anticancer drugs, their adverse side effects and inefficient performances remain ongoing issues. A drug delivery system (DDS) designed for a specific cancer may therefore overcome the drawbacks of single chemotherapeutic drugs and provide precise and synergistical cancer treatment by introducing exclusive stimulus responsiveness and combined chemotherapy properties. Herein, we report the design and synthesis of a supramolecular drug delivery assembly 1 constructed by orthogonal self-assembly technique in aqueous media specifically for application in liver cancer therapy. Complex 1 incorporates the β-cyclodextrin host molecule-functionalized organoplatinum(II) metallacycle 2 with two specific stimulus-responsive motifs to the signaling molecule nitric oxide (NO), in addition to the three-armed polyethylene glycol (PEG) functionalized ferrocene 3 with redox responsiveness. With this molecular design, the particularly low critical aggregation concentration (CAC) of assembly 1 allowed encapsulation of the commercial anticancer drug doxorubicin (DOX). Controlled drug release was also achieved by morphological transfer via a sensitive response to the endogenous redox and NO stimuli, which are specifically related to the microenvironment of liver tumor cells. Upon combination of these properties with the anticancer ability from the platinum acceptor, in vitro studies demonstrated that DOX-loaded 1 is able to codeliver anticancer drugs and exhibit therapeutic effectiveness to liver tumor sites via a synergistic effect, thereby revealing a potential DDS platform for precise liver cancer therapeutics.

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Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics

Current Drug Delivery ◽

10.2174/1567201817999200508092821 ◽

2020 ◽

Vol 17 (7) ◽

pp. 558-576 ◽

Cited By ~ 1

Author(s):

Biman Kumar Panigrahi ◽

Amit Kumar Nayak

Keyword(s):

Carbon Nanotubes ◽

Drug Delivery ◽

Anticancer Drugs ◽

Anticancer Agents ◽

Cancer Therapeutics ◽

Physicochemical Characteristics ◽

Structural Features ◽

Noncovalent Interaction ◽

Bioactive Molecules ◽

Anticancer Drug Delivery

Background: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. Objective: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. Methods: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via the loading of various anticancer agents. Results: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. Conclusion: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

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Telomerase-Targeted Cancer Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms20081823 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1823 ◽

Cited By ~ 15

Author(s):

Eishiro Mizukoshi ◽

Shuichi Kaneko

Keyword(s):

Cancer Cells ◽

Anticancer Drugs ◽

Viral Vectors ◽

Cancer Therapeutics ◽

Current Evidence ◽

Telomerase Reverse Transcriptase ◽

Future Perspectives ◽

Human Telomerase Reverse Transcriptase ◽

Telomerase Inhibitors ◽

Human Telomerase

Telomerase, an enzyme responsible for the synthesis of telomeres, is activated in many cancer cells and is involved in the maintenance of telomeres. The activity of telomerase allows cancer cells to replicate and proliferate in an uncontrolled manner, to infiltrate tissue, and to metastasize to distant organs. Studies to date have examined the mechanisms involved in the survival of cancer cells as targets for cancer therapeutics. These efforts led to the development of telomerase inhibitors as anticancer drugs, drugs targeting telomere DNA, viral vectors carrying a promoter for human telomerase reverse transcriptase (hTERT) genome, and immunotherapy targeting hTERT. Among these novel therapeutics, this review focuses on immunotherapy targeting hTERT and discusses the current evidence and future perspectives.

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Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications

Pharmaceutics ◽

10.3390/pharmaceutics13111887 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1887

Author(s):

Atanu Naskar ◽

Hyejin Cho ◽

Sohee Lee ◽

Kwang-sun Kim

Keyword(s):

Cell Membrane ◽

Outer Membrane ◽

Biomedical Applications ◽

Inner Core ◽

Cancer Therapeutics ◽

Cellular Materials ◽

Outer Membrane Vesicles ◽

Biomimetic Nanoparticles ◽

Bacterial Outer Membrane ◽

New Generation

The biomedical field is currently reaping the benefits of research on biomimetic nanoparticles (NPs), which are synthetic nanoparticles fabricated with natural cellular materials for nature-inspired biomedical applications. These camouflage NPs are capable of retaining not only the physiochemical properties of synthetic nanoparticles but also the original biological functions of the cellular materials. Accordingly, NPs coated with cell-derived membrane components have achieved remarkable growth as prospective biomedical materials. Particularly, bacterial outer membrane vesicle (OMV), which is a cell membrane coating material for NPs, is regarded as an important molecule that can be employed in several biomedical applications, including immune response activation, cancer therapeutics, and treatment for bacterial infections with photothermal activity. The currently available cell membrane-coated NPs are summarized in this review. Furthermore, the general features of bacterial OMVs and several multifunctional NPs that could serve as inner core materials in the coating strategy are presented, and several methods that can be used to prepare OMV-coated NPs (OMV-NPs) and their characterization are highlighted. Finally, some perspectives of OMV-NPs in various biomedical applications for future potential breakthrough are discussed. This in-depth review, which includes potential challenges, will encourage researchers to fabricate innovative and improvised, new-generation biomimetic materials through future biomedical applications.

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Ultrasound-mediated cancer therapeutics delivery using micelles and liposomes: a review

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210706155110 ◽

2021 ◽

Vol 16 ◽

Author(s):

Debasmita Mukhopadhyay ◽

Catherine Sano ◽

Nour AlSawaftah ◽

Rafat El-Awadi ◽

Ghaleb A. Husseini ◽

...

Keyword(s):

Drug Release ◽

Anticancer Drugs ◽

Electromagnetic Waves ◽

Polymeric Micelles ◽

Cancer Therapeutics ◽

Triggering Mechanism ◽

Non Invasive ◽

Metal Organic ◽

Reduced Toxicity ◽

Spatiotemporal Control

Background: Existing cancer treatment methods have many undesirable side effects that greatly reduce the quality of life of cancer patients. Objective: This review will focus on the use of ultrasound-responsive liposomes and polymeric micelles in cancer therapy. Results: Nanoparticles have proven promising as cancer theranostic tools. Nanoparticles are selective in nature, have reduced toxicity and controllable drug release patterns, making them ideal carriers for anticancer drugs. Numerous nanocarriers have been designed to combat malignancies, including liposomes, micelles, dendrimers, solid nanoparticles, quantum dots, gold nanoparticles, and, more recently, metal-organic frameworks. The temporal and spatial release of therapeutic agents from these nanostructures can be controlled using internal and external triggers, including pH, enzymes, redox, temperature, magnetic and electromagnetic waves, and ultrasound. Ultrasound is an attractive modality because it is non-invasive, focused on the diseased site, and has a synergistic effect with anticancer drugs. Conclusion: The functionalization of micellar and liposomal surfaces with targeting moieties and ultrasound as a triggering mechanism can help improve the selectivity and enable the spatiotemporal control of drug release from nanocarriers. Conclusion: The functionalization of micellar and liposomal surfaces with targeting moieties and ultrasound as a triggering mechanism can help improve the selectivity and enable the spatiotemporal control of drug release from nanocarriers.

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Sarcolemmal permeability changes during early myocardial anoxia

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084089 ◽

1978 ◽

Vol 36 (2) ◽

pp. 642-643

Author(s):

M. Ashraf ◽

L. Landa ◽

L. Nimmo ◽

C. M. Bloor

Keyword(s):

Cell Membrane ◽

Membrane Permeability ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Cell Membrane Permeability ◽

Enzyme Release ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Sarcolemmal Permeability ◽

Membrane Changes

Following coronary artery occlusion, the myocardial cells lose intracellular enzymes that appear in the serum 3 hrs later. By this time the cells in the ischemic zone have already undergone irreversible changes, and the cell membrane permeability is variably altered in the ischemic cells. At certain stages or intervals the cell membrane changes, allowing release of cytoplasmic enzymes. To correlate the changes in cell membrane permeability with the enzyme release, we used colloidal lanthanum (La+++) as a histological permeability marker in the isolated perfused hearts. The hearts removed from sprague-Dawley rats were perfused with standard Krebs-Henseleit medium gassed with 95% O2 + 5% CO2. The hypoxic medium contained mannitol instead of dextrose and was bubbled with 95% N2 + 5% CO2. The final osmolarity of the medium was 295 M osmol, pH 7. 4.

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Flagellar Attachment in Selected Trypanosomes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072927 ◽

1973 ◽

Vol 31 ◽

pp. 496-497

Author(s):

J. J. Paulin

Keyword(s):

Cell Membrane ◽

Lateral Surface ◽

The Body ◽

Flagellar Pocket ◽

Integral Component ◽

Free Flagellum ◽

Flagellar Axoneme

Movement in epimastigote and trypomastigote stages of trypanosomes is accomplished by planar sinusoidal beating of the anteriorly directed flagellum and associated undulating membrane. The flagellum emerges from a bottle-shaped depression, the flagellar pocket, opening on the lateral surface of the cell. The limiting cell membrane envelopes not only the body of the trypanosome but is continuous with and insheathes the flagellar axoneme forming the undulating membrane. In some species a paraxial rod parallels the axoneme from its point of emergence at the flagellar pocket and is an integral component of the undulating membrane. A portion of the flagellum may extend beyond the anterior apex of the cell as a free flagellum; the length is variable in different species of trypanosomes.

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