Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents

Nanoscale ◽  
2021 ◽  
Author(s):  
Zhanlin Zhang ◽  
Dandan Zhang ◽  
Bo Qiu ◽  
Wenxiong Cao ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cancer Chemotherapy ◽  
Antineoplastic Agents ◽  
Blood Circulation ◽  
Chemotherapeutic Agents ◽  
Tumor Infiltration ◽  
Intracellular Release ◽  
Pass Through

Cancer chemotherapy remains challenging to pass through various biological and pathological barriers from blood circulation, tumor infiltration and cellular uptake before intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors...

scholarly journals Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

2015 ◽  
Vol 2015 ◽  
pp. 1-22 ◽  
Author(s):  
Roberta Balansin Rigon ◽  
Márcia Helena Oyafuso ◽  
Andressa Terumi Fujimura ◽  
Maíra Lima Gonçalez ◽  
Alice Haddad do Prado ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Antineoplastic Agents ◽  
Blood Circulation ◽  
Drug Delivery Systems ◽  
High Stability ◽  
Controlled Drug Release ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Common Type ◽  
The World

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

scholarly journals In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 394 ◽  
Author(s):  
Viktor Maurer ◽  
Selin Altin ◽  
Didem Ag Seleci ◽  
Ajmal Zarinwall ◽  
Bilal Temel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Superparamagnetic Iron Oxide ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Therapy Outcome ◽  
Ionic Surfactant ◽  
Combinational Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

Vesicle Trafficking, Autophagy and Nanoparticles: A Brief Review

2020 ◽  
Vol 10 (1) ◽  
pp. 3-19
Author(s):  
Tianzhong Li ◽  
Mengsu Yang
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Cellular Uptake ◽  
Vesicle Trafficking ◽  
Endocytic Pathway ◽  
Proton Sponge ◽  
Intracellular Release ◽  
Molecular Machinery ◽  
Delivery Vehicles ◽  
Selection Of

Background: Nanomedicine shows a huge promise for incurable diseases. So far, more than 50 nanoparticles have been approved by FDA and around 80 nanoformulations are currently in clinical trials. Nanoparticles possess several advantages over traditional drugs, including higher biocompatibility and bioavailability. One of the challenges for their wide application is insufficient understanding of the molecular network related to internalization of particles and intracellular release of cargos. Objective: This article aims to review the interactions between nanoparticles, vesicle transportation and autophagy pathways. The underlying molecular machinery is also discussed. Methods: For each step of the vesicle trafficking and autophagy, details of signaling pathways are described for a better understanding of the interactions between delivery vehicles and biomolecules within the cell. Conclusion: The selection of cellular uptake route mainly depends on physical characteristics of nanoparticles. For nanoparticles modified with ligands, they undergo receptormediated endocytic pathway. Once residing within the cells, cargos are released after disruption of endosomes, a mechanism called ‘proton sponge effect’. Besides, internalized nanoparticles either can be exocytosized, or they initiate the autophagy response, affecting the intracellular distribution of drugs.

scholarly journals DDIS-22. DRUG SCREEN IN PATIENT-DERIVED IDHMUT GLIOMA STEM CELLS IDENTIFIES SEVERAL FDA-APPROVED ANTINEOPLASTIC AGENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi67-vi68
Author(s):  
Philip Dao Trong ◽  
Stefan Pusch ◽  
Andreas Unterberg ◽  
Christel Herold-Mende ◽  
Rolf Warta
Keyword(s):  
Stem Cells ◽  
Antineoplastic Agents ◽  
Chemotherapeutic Agents ◽  
Cell Culture Supernatant ◽  
Drug Screen ◽  
Preclinical Model ◽  
Glioma Stem Cells ◽  
Neurosurgical Department ◽  
Stable Production ◽  
Approved Drugs

Abstract OBJECTIVE The discovery of the Isocitrate Dehydrogenase (IDH) mutation in glioma has led to a paradigm shift on how we see glioma biology. While it is clear, that IDH mutated (IDHmut) and wildtype (IDHwt) tumors have to be viewed as separate entities, the underlying biological differences are still matter of extensive research. Difficulties in cultivating IDHmut glioma stem cells (GSC) have led to a paucity of preclinical models in IDHmut glioma making the discovery of new effective chemotherapeutic agents problematic. We therefore sought to perform a repurposing drug screen in five patient-derived IDHmut GSC lines to discover potential effective antineoplastic agents, already approved by the FDA. METHODS Patient tumor tissue was obtained in our neurosurgical department to isolate and establish IDHmut GSC lines. (D)-2-hydroxyglutarate (2HG) levels were measured in the cell culture supernatant of IDHmut GSCs using an enzymatic diaphorase/resazurin system. The drug library provided by the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) consisting of 146 FDA-approved drugs was used for the screen. Cell viability was assessed with the CellTiterGlo assay (Promega). RESULTS Despite several passages, the IDHmut GSCs showed stable production of 2HG and were therefore suitable for the drug screen. Cells were cultured as neurospheres and subjected to the test compounds for 72h in concentrations ranging from 0.1nM – 1µM. We identified several compounds in two IDHmut GSC lines (NCH551b, NCH1681) that had a half maximal inhibitory concentration (IC50) below 1µM and could confirm its cytotoxic potential in additional three IDHmut GSC lines (NCH612, NCH620, NCH3763). CONCLUSION In this study, we present a feasible preclinical model for a high-throughput drug screen in patient-derived IDHmut GSCs and identified several FDA-approved antineoplastic agents which warrant further investigations.

scholarly journals Transferrin/α-tocopherol modified poly(amidoamine) dendrimers for improved tumor targeting and anticancer activity of paclitaxel

Nanomedicine ◽  
2019 ◽  
Vol 14 (24) ◽  
pp. 3159-3176
Author(s):  
Himanshu Bhatt ◽  
Sri Vishnu Kiran Rompicharla ◽  
Balaram Ghosh ◽  
Vladimir Torchilin ◽  
Swati Biswas
Keyword(s):  
Epithelial Cells ◽  
Cellular Uptake ◽  
Delivery System ◽  
Targeted Delivery ◽  
Chemotherapeutic Agents ◽  
Efficient Delivery ◽  
Tocopheryl Succinate ◽  
Cervical Epithelial Cells ◽  
Poly Ethylene ◽  
3D Spheroids

Aim: Transferrin anchored, poly(ethylene glycol) (PEG) and α-tocopheryl succinate (α-TOS) conjugated generation 4 dendrimer has been prepared in order to develop a tumor targeted delivery system of a hydrophobic chemotherapeutic agent, paclitaxel (PTX). Materials & methods: The dendrimers were characterized physicochemically for size, ζ and encapsulation ability. The cellular uptake, cytotoxicity potential and apoptosis of prepared nanoconstruct were evaluated in human cervical epithelial cells monolayer and 3D spheroids. Results & conclusion: G4-TOS-PEG-Tf demonstrated increased cellular uptake, cytotoxicity and apoptotic potential of PTX compared with free PTX and G4-TOS-PEG-PTX. G4-TOS-PEG-Tf-PTX inhibited growth of human cervical epithelial cells spheroids significantly. The newly developed dendrimers hold promise as an efficient delivery system for PTX or other hydrophobic chemotherapeutic agents for targeted delivery to tumors.

scholarly journals A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Bina Gidwani ◽  
Amber Vyas
Keyword(s):  
Anticancer Drugs ◽  
Delivery System ◽  
Antineoplastic Agents ◽  
Aqueous Solubility ◽  
Chemotherapeutic Agents ◽  
Review Article ◽  
Administration Routes ◽  
Cyclodextrin Complexation ◽  
Important Approach ◽  
Biopharmaceutical Properties

Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents.

Cellular uptake and intracellular release are major obstacles to the therapeutic application of siRNA: novel options by phosphorothioate-stimulated delivery

2007 ◽  
Vol 7 (10) ◽  
pp. 1531-1538 ◽  
Author(s):  
Alessandra Mescalchin ◽  
Anke Detzer ◽  
Maria Wecke ◽  
Marita Overhoff ◽  
Winfried Wünsche ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Therapeutic Application ◽  
Intracellular Release

MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs

2020 ◽  
Vol 7 (2) ◽  
pp. 65-77
Author(s):  
Noor Altaleb
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Chemotherapy ◽  
Mirna Expression ◽  
Chemotherapeutic Agents ◽  
Tumour Suppressor ◽  
New Approach ◽  
Cancer Data ◽  
Fundamental Units

Although there are no 100% successful methods for treating cancer, chemotherapy is still one of the most commonly used approaches in its management. One of the most significant problems in cancer treatment is the resistance of cancer cells to chemotherapeutic agents. This review aims to unveil the factors contributing to this problem originally beginning with fundamental units like biomarkers and microRNAs. As more studies and researches carried out, various levels of miRNA expression were found among normal and cancer cells. Overexpression of oncomir and downregulation of tumour-suppressor miRNAs can lead to the emergence of cancer. Data collected from studying these miRNAs can help in the diagnosis, prognosis and developing therapies, which will assist in overcoming the emerged resistance.

Cancer Chemotherapy

PEDIATRICS ◽  
1967 ◽  
Vol 40 (6) ◽  
pp. 1070-1071
Author(s):  
THOMAS E. HALL
Keyword(s):  
Cancer Chemotherapy ◽  
Chemical Treatment ◽  
Chemotherapeutic Agents ◽  
Modes Of Action

In the two decades since the effective chemical treatment of cancer began to emerge there have been few books published which review what can be accomplished by chemotherapy. Dr. Greenwald's book will be of particular value to the practitioner interested in cancer chemotherapy because the approach, though clinically oriented, is thorough and is based on sound pharmacologic principles. The plan of the book is first to discuss the pharmacologic properties of the currently available chemotherapeutic agents, then modes of action of the several classes of drugs:

Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells

2018 ◽  
Vol 65 ◽  
pp. 339-348 ◽  
Author(s):  
Hanlin Ou ◽  
Tangjian Cheng ◽  
Yumin Zhang ◽  
Jinjian Liu ◽  
Yuxun Ding ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cellular Uptake ◽  
Blood Circulation ◽  
Circulation Time
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