Hydrogen-bonded supramolecular micelle-mediated drug delivery enhances the efficacy and safety of cancer chemotherapy

2020 ◽  
Vol 11 (16) ◽  
pp. 2791-2798
Author(s):  
Chih-Chia Cheng ◽  
Ya-Ting Sun ◽  
Ai-Wei Lee ◽  
Shan-You Huang ◽  
Wen-Lu Fan ◽  
...  

Multiple hydrogen-bonded supramolecular polymers tend to form stable spherical micelles with oppositely charged anticancer drugs in biological environments, which improves cellular drug uptake and more effectively induces apoptosis in cancer cells.

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Ka Yaw Teo ◽  
Bumsoo Han

The efficacy of chemotherapy is significantly impaired by the multidrug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain adenosine triphosphate-binding cassette protein transporters in plasma membranes, which actively pump out cytotoxic drugs from the intracellular space. In this study, we tested a hypothesis that freezing and thawing (F/T) may enhance intracellular drug delivery to MDR cancer cells via F/T-induced denaturation of MDR-associated proteins and/or membrane permeabilization. After a human MDR cancer cell line (NCI/ADR-RES) was exposed to several F/T conditions, its cellular drug uptake was quantified by a fluorescent calcein assay using calcein as a model drug. After F/T to −20°C, the intracellular uptake of calcein increased by 70.1% (n=5, P=0.0004). It further increased to 118% as NCI/ADR-RES cells were frozen/thawed to −40°C (n=3, P=0.009). These results support the hypothesis, and possible mechanisms of F/T-enhanced intracellular drug delivery were proposed and discussed.


2019 ◽  
Vol 20 (13) ◽  
pp. 1087-1107 ◽  
Author(s):  
Hasanain Gomhor J. Alqaraghuli ◽  
Soheila Kashanian ◽  
Ronak Rafipour

Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.


2020 ◽  
Vol 7 (2) ◽  
pp. 65-77
Author(s):  
Noor Altaleb

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1929
Author(s):  
Fasih Bintang Ilhami ◽  
Enyew Alemayehu Bayle ◽  
Chih-Chia Cheng

A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic drug adenine-modified rhodamine (A-R6G). This concept holds promise as a smart and versatile drug delivery system for the achievement of targeted, more efficient cancer chemotherapy. Due to A–U base pairing between BU-PEG and A-R6G, BU-PEG has high tendency to interact with A-R6G, which leads to the formation of self-assembled A-R6G/BU-PEG nanogels in aqueous solution. The resulting nanogels exhibit a number of unique physical properties, including extremely high A-R6G-loading capacity, well-controlled, pH-triggered A-R6G release behavior, and excellent structural stability in biological media. Importantly, a series of in vitro cellular experiments clearly demonstrated that A-R6G/BU-PEG nanogels improved the selective uptake of A-R6G by cancer cells via endocytosis and promoted the intracellular release of A-R6G to subsequently induce apoptotic cell death, while control rhodamine/BU-PEG nanogels did not exert selective toxicity in cancer or normal cell lines. Overall, these results indicate that cooperative A–U base pairing within nanogels is a critical factor that improves selective drug uptake and effectively promotes apoptotic programmed cell death in cancer cells.


2012 ◽  
Vol 67 (3) ◽  
pp. 23-31 ◽  
Author(s):  
A. Yu. Baryshnikov

Liposomes quite recently have turned from a model of biological membranes into an object of extensive research and practical use. The versatile traits of liposomal formulation allow its' universal implementation, especially in cancer chemotherapy. The advantages of liposomal use as a carrier of an anticancer drug for its targeted selective accumulation are discussed in this article. This article contains description of new types of liposomes, differing in contents and use, such as: simple, sterically stabilized, targeted (immunoliposomes),cationic, sensitive to physical and chemical stimuli. The characteristics of liposomal systems of anticancer drug delivery designed at Blokhin Russian Oncological Scientific Centre is given in the article.


Polymers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 578 ◽  
Author(s):  
Justin Horn ◽  
Rachel Kapelner ◽  
Allie Obermeyer

Protein-containing polyelectrolyte complexes (PECs) are a diverse class of materials, composed of two or more oppositely charged polyelectrolytes that condense and phase separate near overall charge neutrality. Such phase-separation can take on a variety of morphologies from macrophase separated liquid condensates, to solid precipitates, to monodispersed spherical micelles. In this review, we present an overview of recent advances in protein-containing PECs, with an overall goal of defining relevant design parameters for macro- and microphase separated PECs. For both classes of PECs, the influence of protein characteristics, such as surface charge and patchiness, co-polyelectrolyte characteristics, such as charge density and structure, and overall solution characteristics, such as salt concentration and pH, are considered. After overall design features are established, potential applications in food processing, biosensing, drug delivery, and protein purification are discussed and recent characterization techniques for protein-containing PECs are highlighted.


2010 ◽  
Vol 20 (01n02) ◽  
pp. 37-43 ◽  
Author(s):  
K. MIZUNO ◽  
M. UESAKA ◽  
S. MATSUYAMA ◽  
Y. ITO ◽  
K. ISHII ◽  
...  

Highly functionalized drugs delivered via a drug delivery system are expected to have less side effects and higher accumulation rates compared to conventional anticancer drugs. An understanding of the kinetics of drugs contained within a delivery system is necessary to obtain the maximum therapeutic effect. We performed micro-elemental analysis of human pancreatic cancer cells treated with cis-diamminedichloroplatinum(II) (CDDP)-containing polymeric micelles. The results showed that the platinum signals were distributed inside the cellular nuclei and the cytoplasm indicating that CDDP was delivered into the cells. The results from this study will be useful for designing an optimum carrier for platinum-containing anticancer drugs.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Changzhen Sun ◽  
Ji Lu ◽  
Jun Wang ◽  
Ping Hao ◽  
Chunhong Li ◽  
...  

Abstract Background Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. Results To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells. Conclusions A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Kohji Noguchi ◽  
Yoshikazu Sugimoto

Multidrug resistance (MDR) in cancer cells is a phenotype whereby cells display reduced sensitivity to anticancer drugs, based on a variety of mechanisms, including an increase in drug efflux, the reduction of drug uptake, the activation of cell growth and survival signaling, the promotion of DNA repair, and the inhibition of apoptosis signaling. Increased expression of the plasma membrane drug efflux pumps, the ATP-binding cassette (ABC) transporters, is involved in MDR. P-Glycoprotein/ABCB1 is a member of the ABC transporter family, and facilitates the efflux of various anticancer drugs, including anthracyclines, vinca alkaloids, epipodophyllotoxins, taxanes, and kinase inhibitors, from cells. P-Glycoprotein is also expressed in normal tissues and cells, including the kidney, liver, colon, and adrenal gland, to transport and/or secrete substrates and at the blood-brain, blood-placenta, and blood-testis barriers to protect these tissues from toxic substances. To understand the mechanistic functions of P-glycoprotein and to overcome MDR, investigators have identified the substrates and competitive inhibitors of P-glycoprotein. Recently, we and other groups reported associations between cellular signaling pathways and the expression, stability, degradation, localization, and activity of P-glycoprotein. The present review summarizes the currently available information about the transcriptional and posttranslational regulation of P-glycoprotein expression and function.


2020 ◽  
Author(s):  
Changzhen Sun ◽  
Ji Lu ◽  
Jun Wang ◽  
Ping Hao ◽  
Chunhong Li ◽  
...  

Abstract Background: Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject.Results: To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells.Conclusions: A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.


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