scholarly journals Cyclodextrin-Based Hybrid Polymeric Complex to Overcome Dual Drug Resistance Mechanisms for Cancer Therapy

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1254
Author(s):  
Lingjie Ke ◽  
Zhiguo Li ◽  
Xiaoshan Fan ◽  
Xian Jun Loh ◽  
Hongwei Cheng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Gene Delivery ◽  
Cell Membrane ◽  
Inclusion Complex ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Resistance Mechanisms ◽  
Polymeric Complex ◽  
Cavity Structure ◽  
Dual Drug

Drug resistance always reduces the efficacy of chemotherapy, and the classical mechanisms of drug resistance include drug pump efflux and anti-apoptosis mediators-mediated non-pump resistance. In addition, the amphiphilic polymeric micelles with good biocompatibility and high stability have been proven to deliver the drug molecules inside the cavity into the cell membrane regardless of the efflux of the cell membrane pump. We designed a cyclodextrin (CD)-based polymeric complex to deliver chemotherapeutic doxorubicin (DOX) and Nur77ΔDBD gene for combating pumps and non-pump resistance simultaneously. The natural cavity structure of the polymeric complex, which was comprised with β-cyclodextrin-graft-(poly(ε-caprolactone)-adamantly (β-CD-PCL-AD) and β-cyclodextrin-graft-(poly(ε-caprolactone)-poly(2-(dimethylamino) ethyl methacrylate) (β-CD-PCL-PDMAEMA), can achieve the efficient drug loading and delivery to overcome pump drug resistance. The excellent Nur77ΔDBD gene delivery can reverse Bcl-2 from the tumor protector to killer for inhibiting non-pump resistance. The presence of terminal adamantyl (AD) could insert into the cavity of β-CD-PCL-PDMAEMA via host-guest interaction, and the releasing rate of polymeric inclusion complex was higher than that of the individual β-CD-PCL-PDMAEMA. The polymeric inclusion complex can efficiently deliver the Nur77ΔDBD gene than polyethylenimine (PEI-25k), which is a golden standard for nonviral vector gene delivery. The higher transfection efficacy, rapid DOX cellular uptake, and significant synergetic tumor cell viability inhibition were achieved in a pump and non-pump drug resistance cell model. The combined strategy with dual drug resistance mechanisms holds great potential to combat drug-resistant cancer.

Polymeric complex micelles based on the double-hydrazone linkage and dual drug-loading strategy for pH-sensitive docetaxel delivery

2016 ◽  
Vol 4 (6) ◽  
pp. 1122-1133 ◽  
Author(s):  
Zhihui Su ◽  
Yanchao Liang ◽  
Yao Yao ◽  
Tianqi Wang ◽  
Na Zhang
Keyword(s):  
Drug Loading ◽  
Ph Sensitive ◽  
Polymeric Complex ◽  
Loading Patterns ◽  
First Time ◽  
Complex Micelles ◽  
Dual Drug

Complex micelles, which integrated double-hydrazone linkage and dual drug-loading patterns, were constructed for the first time.

Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Clinical Applications ◽  
Current Status ◽  
Cancer Drug ◽  
Genomic Alteration ◽  
Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

Dissecting the landscape of CAF-mediated drug resistance mechanisms in ALK-rearranged NSCLC

2020 ◽  
Vol 138 ◽  
pp. S48
Author(s):  
Q. Hu ◽  
L.L. Remsing Rix ◽  
X. Li ◽  
E.A. Welsh ◽  
B. Fang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mechanisms

scholarly journals Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Zhang ◽  
Fanghua Zhang ◽  
Mengnan Han ◽  
Xuming Wang ◽  
Jie Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Antitumor Activity ◽  
Solid Phase ◽  
Clinical Care ◽  
Drug Loading ◽  
Her2 Positive ◽  
Apoptosis Pathway ◽  
Phase Synthesis ◽  
Drug Nanocarriers ◽  
Dual Drug

AbstractCombination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2+ cancer.

Present trends in the encapsulation of anticancer drugs

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Xavier Montané ◽  
Karolina Matulewicz ◽  
Karolina Balik ◽  
Paulina Modrakowska ◽  
Marcin Łuczak ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Drug Toxicity ◽  
Recent Progress ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
The Body ◽  
Inorganic Nanoparticles ◽  
Hybrid Nanoparticles ◽  
Traditional Medicines ◽  
Low Solubility

Abstract Different nanomedicine devices that were developed during the recent years can be suitable candidates for their application in the treatment of various deadly diseases such as cancer. From all the explored devices, the nanoencapsulation of several anticancer medicines is a very promising approach to overcome some drawbacks of traditional medicines: administered dose of the drugs, drug toxicity, low solubility of drugs, uncontrolled drug delivery, resistance offered by the physiological barriers in the body to drugs, among others. In this chapter, the most important and recent progress in the encapsulation of anticancer medicines is examined: methods of preparation of distinct nanoparticles (inorganic nanoparticles, dendrimers, biopolymeric nanoparticles, polymeric micelles, liposomes, polymersomes, carbon nanotubes, quantum dots, and hybrid nanoparticles), drug loading and drug release mechanisms. Furthermore, the possible applications in cancer prevention, diagnosis, and cancer therapy of some of these nanoparticles have been highlighted.

scholarly journals Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

2021 ◽  
Vol 11 (5) ◽  
pp. 663
Author(s):  
Elena D. Bazhanova ◽  
Alexander A. Kozlov ◽  
Anastasia V. Litovchenko
Keyword(s):  
Drug Resistance ◽  
Premature Death ◽  
Resistance Mechanisms ◽  
Biomedical Literature ◽  
Drug Resistant ◽  
Psychological Consequences ◽  
Text Documents ◽  
Neural Connections ◽  
Inflammatory Processes ◽  
Drug Resistant Epilepsy

Epilepsy is a chronic neurological disorder characterized by recurring spontaneous seizures. Drug resistance appears in 30% of patients and it can lead to premature death, brain damage or a reduced quality of life. The purpose of the study was to analyze the drug resistance mechanisms, especially neuroinflammation, in the epileptogenesis. The information bases of biomedical literature Scopus, PubMed, Google Scholar and SciVerse were used. To obtain full-text documents, electronic resources of PubMed Central and Research Gate were used. The article examines the recent research of the mechanisms of drug resistance in epilepsy and discusses the hypotheses of drug resistance development (genetic, epigenetic, target hypothesis, etc.). Drug-resistant epilepsy is associated with neuroinflammatory, autoimmune and neurodegenerative processes. Neuroinflammation causes immune, pathophysiological, biochemical and psychological consequences. Focal or systemic unregulated inflammatory processes lead to the formation of aberrant neural connections and hyperexcitable neural networks. Inflammatory mediators affect the endothelium of cerebral vessels, destroy contacts between endothelial cells and induce abnormal angiogenesis (the formation of “leaky” vessels), thereby affecting the blood–brain barrier permeability. Thus, the analysis of pro-inflammatory and other components of epileptogenesis can contribute to the further development of the therapeutic treatment of drug-resistant epilepsy.

scholarly journals Functional Genomics Approaches to Elucidate Vulnerabilities of Intrinsic and Acquired Chemotherapy Resistance

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 260
Author(s):  
Ronay Cetin ◽  
Eva Quandt ◽  
Manuel Kaulich
Keyword(s):  
Drug Resistance ◽  
Acquired Resistance ◽  
Chemotherapy Resistance ◽  
Resistance Mechanisms ◽  
Therapy Failure ◽  
Tightly Coupled ◽  
Unbiased Gene ◽  
Multiple Drugs ◽  
Genome Scale ◽  
Gene Perturbations

Drug resistance is a commonly unavoidable consequence of cancer treatment that results in therapy failure and disease relapse. Intrinsic (pre-existing) or acquired resistance mechanisms can be drug-specific or be applicable to multiple drugs, resulting in multidrug resistance. The presence of drug resistance is, however, tightly coupled to changes in cellular homeostasis, which can lead to resistance-coupled vulnerabilities. Unbiased gene perturbations through RNAi and CRISPR technologies are invaluable tools to establish genotype-to-phenotype relationships at the genome scale. Moreover, their application to cancer cell lines can uncover new vulnerabilities that are associated with resistance mechanisms. Here, we discuss targeted and unbiased RNAi and CRISPR efforts in the discovery of drug resistance mechanisms by focusing on first-in-line chemotherapy and their enforced vulnerabilities, and we present a view forward on which measures should be taken to accelerate their clinical translation.

LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

2021 ◽  
Author(s):  
Yupei Ma ◽  
Du Li ◽  
Yunchao Xiao ◽  
Zhijun OuYang ◽  
Mingwu Shen ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Side Effect ◽  
Drug Loading ◽  
Adverse Side Effect ◽  
Drug Resistant ◽  
Short Fibers ◽  
Dual Drug

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...

Bmk9 and Uricase Nanoparticle Complex for the Treatment of Gouty Arthritis and Uric Acid Nephropathy

2021 ◽  
Vol 17 (10) ◽  
pp. 2071-2084
Author(s):  
Tianjiao Han ◽  
Meiying Wang ◽  
Wenchao Li ◽  
Mingxing An ◽  
Hongzheng Fu
Keyword(s):  
Uric Acid ◽  
Drug Loading ◽  
Gouty Arthritis ◽  
The Body ◽  
Key Points ◽  
Uric Acid Nephropathy ◽  
Charged Carrier ◽  
Dual Drug

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.

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