Modulating the cellular uptake of platinum drugs with glycopolymers

2016 ◽  
Vol 7 (5) ◽  
pp. 1031-1036 ◽  
Author(s):  
Aydan Dag ◽  
Manuela Callari ◽  
Hongxu Lu ◽  
Martina H. Stenzel

The therapeutic potency of platinum-based anticancer drugs can be substantially improved through the use of fructose-coated nanocarrier systems to target cancer cells efficiently.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 680
Author(s):  
Jin Zhang ◽  
Xiaoyue Tang ◽  
Chuanqing Huang ◽  
Zeyu Liu ◽  
Yong Ye

Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA and o-nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF4:Yb3+/Er3+ nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.


TAYACAJA ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 193-202
Author(s):  
Jorge L. Gutierrez-Pajares ◽  
Amr Abdelkhalek

Cancer is a worldwide disease that affects millions of people every year. Although there are several approved chemotherapeutic drugs for cancer treatment, there is s constant search for new molecules. This search is supported by the need of new molecules that could target cancer cells specifically reducing side effects or that could act synergistically with approved anticancer drugs. In this review, research on flower extracts and flower-derived molecules is presented.


2021 ◽  
Vol 14 (2) ◽  
pp. 133
Author(s):  
Suxing Jin ◽  
Yan Guo ◽  
Zijian Guo ◽  
Xiaoyong Wang

Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl]+ (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs.


2008 ◽  
Vol 8 (5) ◽  
pp. 2301-2307
Author(s):  
Dadong Guo ◽  
Chunhui Wu ◽  
Xiaomao Li ◽  
Hui Jiang ◽  
Xuemei Wang ◽  
...  

Nickel nanoparticles (Ni NPs) have been applied in a wide range of areas because of their unique structure and properties such as catalysts, high-density magnetic recording media and others. However, little effort has been paid to their biological application and the concrete effect of Ni NPs on biological systems is still unknown. In this study, the possibility of the utilization of the magnetic Ni NPs in cancer cell studies was explored and the effects of the Ni NPs capped with positively charged tetraheptylammonium on leukemia K562 cells in vitro were investigated. Our observations of optical microscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM) studies indicate that the morphological changes of cancer cells induced by Ni NPs could be apparently observed. The results of 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay, DNA fragmentation and flow cytometry studies demonstrate that the Ni NPs could exert cytotoxicity to leukemia K562 cells at high concentration, and subsequently induce both apoptosis and necrosis of target cancer cells, whilst it had little impact on target cells when at low concentration. Meanwhile, functionalized Ni NPs with positively charged groups could enhance the permeability of cell membrane and facilitate the cellular uptake of outer target molecules into cancer cells. These findings reveal the potential mechanism of Ni NPs to target cancer cells which could induce the cytotoxicity to leukemia cancer cells and suggest the possibility for applications of the Ni NPs in related clinical and biomedical areas.


2020 ◽  
Vol 21 (13) ◽  
pp. 4677 ◽  
Author(s):  
Yihalem Abebe Alemayehu ◽  
Wen-Lu Fan ◽  
Fasih Bintang Ilhami ◽  
Chih-Wei Chiu ◽  
Duu-Jong Lee ◽  
...  

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.


2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.


Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.


2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.


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