<scp>CD</scp>44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

Goodarzi, Navid; Ghahremani, Mohammad H.; Amini, Mohsen; Atyabi, Fatemeh; Ostad, Seyed Nasser; Ravari, Nazanin Shabani; Nateghian, Navid; Dinarvand, Rassoul

doi:10.1111/cbdd.12288

Cited by 64 publications

(33 citation statements)

References 53 publications

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“…The cytotoxicity and antiproliferative activity assays of DG and the synthesized Arg-DG conjugate were performed in L929 and HepG2 cells using the tetrazolium salt 3-[4,5-di methylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. [27] Cells were seeded in 96-well plates at a density of 10,000 cells/ml, preincubated at 37°C, and then exposed to the samples. After a 48 hr treatment, the cell proliferation was measured using the MTT assay according to the manufacturer's recommendations.…”

Section: Proliferation Assaymentioning

confidence: 99%

“…[32] The results manifested that the Arg-DG conjugate exhibited a more beneficial profile for potential development as an antiproliferative drug for hepatocellular carcinoma than DG. [27] The Arg-DG conjugate showed improved solubility, which increased the available drug concentration inside the cells. These results suggest the probable mechanisms that underlie the improved antiproliferative activity of the Arg-DG conjugate.…”

Section: Cytotoxicity and Antiproliferative Activity Of Arg-dg Conjmentioning

confidence: 99%

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Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Liao

Jung

et al. 2017

Chem Biol Drug Des

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Water-soluble arginyl-diosgenin (Arg-DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg-DG conjugate was characterized using FT-IR, 1 H NMR, 13 C NMR, and HPLC-MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg-DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg-DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg-DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg-DG conjugate improved the bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg-DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering. K E Y W O R D SALP assay, arginyl-diosgenin conjugate, bone tissue engineering, cytotoxicity, tube formation assay | INTRODUCTIONDiosgenin [(25R)-spirost-5-en-3ß-ol] (DG) is a major naturally occurring steroid saponin, which is abundantly distributed in the rootstock of yams (Dioscorea sp.) and other plants such as Smilax bockii warb and Trigonella foenum graecum. [1,2] DG has exhibited biological effects in the treatment of various diseases such as hypercholesterolemia, climacteric syndromes including diabetic neuropathy and even cancer. [3][4][5][6] It has also been claimed to have an osteogenic property. DG was reported to inhibit osteoclastogenesis and enhance osteoblastic cell differentiation and the synthesis of cellular bone matrix protein. [7,8] It has been hypothesized that DG could be a potential activator of bone formation and potential therapeutic agent for bone-related diseases including osteoporosis.[8]However, the medical application of DG is considerably limited because of its solubility problem and associated toxicity. The aqueous solubility of DG was determined to be 0.7 ng/ml (1.69 nm).[9] It was also revealed that the low solubility of DG led to poor bioavailability and gastrointestinal mucosal toxicity. [10] As poor solubility has been recognized as a frequently encountered challenge in the field of pharmaceutics, different approaches have been employed to improve the solubility and bioavailability of poorly watersoluble compounds including DG. [11] For instance, an inclusion of complexation of DG and β-cyclodextrin was formed. [12] Iron oxide nanoparticles loaded with DG were prepared. [13] Improving the solubility of DG and decreasing its intrinsic cytotoxicity or at least avoiding any additional toxicity against normal cells are the major challenges to its biomedical application. Numerous efforts have been made to chemically modify this compound to improve its applicable biological activities. Diosgenyl saponin, dioscin analogues were designed to improve its anticancer a...

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Section: Proliferation Assaymentioning

confidence: 99%

Section: Cytotoxicity and Antiproliferative Activity Of Arg-dg Conjmentioning

confidence: 99%

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Liao

Jung

et al. 2017

Chem Biol Drug Des

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“…Unlike common polymeric carriers such as PEG and HPMA, HA has an innate ability to target cancer cells through strong interaction with the CD44 receptor over expressed in many cancers [37–40]. While many normal cells express CD44, including T and B cells, the CD44 normally exists in a glycosolated low-affinity form.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan-Lysine Cisplatin Drug Carrier for Treatment of Localized Cancers: Pharmacokinetics, Tolerability, and Efficacy in Rodents and Canines

Zhang

Cai

Groer³

et al. 2016

Journal of Pharmaceutical Sciences

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The purpose of this study was to develop a safe and efficacious drug delivery platform for sustained release of cisplatin after locoregional administration. We successfully synthesized hyaluronan-cisplatin nanoconjugates (HA-Lys-Pt) using an N-Ac-lysine linker, which formed a thermodynamically stable 5-membered ring with the platinum. The conjugate was characterized for release kinetics, in vitro anti-proliferative activity, degradability, impurity content, formation of Pt-DNA adducts, pharmacokinetics, tolerability in rodents and canines, and for efficacy in rodents. The 75kD HA-Lys-Pt (75HALys-Pt) sustained release of platinum with a 69 hour half-life in phosphate buffered saline without substantial burst release. Compared to intravenous cisplatin, subcutaneously injected 75HA-Lys-Pt formed 3.2-fold more Pt-DNA adducts in rat peripheral blood mononuclear cells compared to intravenous cisplatin over 96 hours. Subcutaneous 75HA-Lys-Pt was tolerable in rats at 40 mg/kg (4× the LD50 of conventional cisplatin) and resulted in 62.5% partial response and 37.5% stable disease in murine xenografts of head and neck squamous cell cancer (20 mg/kg/wk × 3 wk). 75HA-Lys-Pt demonstrated extended tmax and improved area-under-the-curve compared to cisplatin in rats and canines. Canine safety was demonstrated by liver enzyme and electrolyte levels, complete blood count, and urinalysis.

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“…As classification has been primarily based on histology of tumor, targeted therapy has not been effective in treating tumors with similar histology [6, 227]. Similarly, several Dtx derivatives with better targetibility and stability were developed such as CD44 targeted-hyaluronic acid based derivatives [228]. Sun and co-workers reported a prodrug with fluorinated Dtx conjugated to rhodamine B (imaging reporter/targeting domain) through a biodegradable ester linkage.…”

Section: Prodrug Approach: Analog / Chemical Conjugation For Cancementioning

confidence: 99%

Novel delivery approaches for cancer therapeutics

Mitra

Agrahari

Mandal

et al. 2015

Journal of Controlled Release

138

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Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering, multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer.

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CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

Cited by 64 publications

References 53 publications

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Hyaluronan-Lysine Cisplatin Drug Carrier for Treatment of Localized Cancers: Pharmacokinetics, Tolerability, and Efficacy in Rodents and Canines

Novel delivery approaches for cancer therapeutics

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