Adamantane–platinum conjugate hosted in β-cyclodextrin: Enhancing transport and cytotoxicity by noncovalent modification

Prashar, Deepali; Shi, Yi; Bandyopadhyay, Debjyoti; Dabrowiak, James C.; Luk, Yan Yeung

doi:10.1016/j.bmcl.2011.10.006

Cited by 20 publications

(14 citation statements)

References 40 publications

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“…Factors such as intracellular transport, receptor binding, and heterogeneous distributions inside cells seem to play more important roles than just the cellular uptake for the cytotoxic effect of the drug. 74 Water-insoluble trans-dichloro(dipyridine)platinum(II) is difficult to be used in biological settings. The encapsulation of this complex with bCD increases its solubility to 1.6 mg mL À1 .…”

Section: Carbohydrates As Carriersmentioning

confidence: 99%

Targeting and delivery of platinum-based anticancer drugs

2013

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Platinum-based anticancer drugs occupy a crucial role in the treatment of various malignant tumours. However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance. Different drug targeting and delivery (DTD) strategies have been developed to prevent the shortcomings of platinum-based chemotherapy. These approaches can be roughly categorized into two groups; namely, active and passive tactics. Active DTD is realized through specific molecular interactions between the drugs and cell or tissue elements, while passive DTD is achieved by exploiting the enhanced permeability and retention effect in tumour tissues. The principal methods for active DTD include conjugation of platinum drugs with selective targeting moieties or encapsulation of platinum drugs in host molecules. Bioactive substances such as hormones, carbohydrates, bisphosphonates, peptides and proteins are commonly used in active DTD. Passive DTD generally involves the fabrication of functionalized polymers or nanoparticles and the subsequent conjugation of platinum drugs with such entities. Polymeric micelles, liposomes, nanotubes and nanoparticles are frequently used in passive DTD. In some cases, both active and passive mechanisms are involved in one DTD system. This review concentrates on various targeting and delivery techniques for improving the efficacy and reducing the side effects of platinum-based anticancer drugs. The content covers most of the related literatures published since 2006. These innovative tactics represent current state-of-the-art developments in platinum-based anticancer drugs.

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Section: Carbohydrates As Carriersmentioning

confidence: 99%

Targeting and delivery of platinum-based anticancer drugs

2013

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“…A number of n-cyclodextrin host-guest complexes have been reported with platin compounds (Prashar et al 2011, although only one studied the ability of the macrocycle to slow platin drug degradation (Krause-Heuer et al 2008). The partial encapsulation of three different platin agents by a carboxylated form of b-cyclodextrin slowed their degradation by glutathione by at least threefold.…”

Section: N-cyclodextrinsmentioning

confidence: 99%

The state-of-play and future of platinum drugs

Apps

Choi

Wheate

2015

Endocrine-Related Cancer

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The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of cisplatin and it remains just as useful now as it did back then, especially for the treatment of some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, five other platin drugs have received approval in various countries. While several new platin drugs are in preclinical development, in the last decade only two new platin drugs have entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles. In addition to drug delivery, functional genomics is now playing an increasing role in predicting patients' responses to platin chemotherapy and their likelihood of experiencing severe side effects.

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“…DMSO can be toxic and has been found to negatively affect the activity of some platinum drugs in vitro . On one hand, recent results have led to the suggestion that cyclodextrins can enhance transport and cytotoxicity by forming inclusion complexes with various drugs. − However, a strong interaction between the drug of interest and cyclodextrin can lead to a decreased cellular uptake and a loss of activity . We thus decided to test 2 and 11 against A549 cells using stock solutions prepared with either dimethyl sulfoxide (DMSO) or water containing β-CD as a formulating agent.…”

Section: Resultsmentioning

confidence: 99%

Platinum(IV)-Ferrocene Conjugates and Their Cyclodextrin Host–Guest Complexes

et al. 2019

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Reported here are new platinum(IV) (Pt(IV)) complexes bearing ferrocene (Fc) moieties. These systems differ from one another only by the nature of the functional group (ester vs amide) connecting the linker to the Fc subunits. This minor structural variation (one atom difference) leads to major differences in solubility, stability, and antiproliferative activity against lung (A549) cancer cells. The host-guest chemistry of these complexes was investigated in an aqueous medium in the presence of β-cyclodextrins (β-CD), either free or in the form of a covalently linked Fc-Ptβ-CD hybrid. An inclusion complex between Fc and β-CD is formed in aqueous media, presumably as a result of hydrophobic interactions involving the Fc and the inner β-CD cavity. Consequently, it proved possible to use a β-CD-based strategy to purify the Pt-Fc conjugates in this study under aqueous conditions (by means of C18 silica gel columns). The use of a β-CD adjuvant also allowed dimethyl sulfoxide (DMSO) to be avoided as an organic cosolvent in cell studies. The amide version reported here (2) proved to be more soluble, more stable, and more active than the ester analogue (11) in A549 cells. The use of a β-CD functionalized with a fluorescent probe allowed intracellular Pt-Fc localization to be visualized by confocal fluorescence microscopy.

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Adamantane–platinum conjugate hosted in β-cyclodextrin: Enhancing transport and cytotoxicity by noncovalent modification

Cited by 20 publications

References 40 publications

Targeting and delivery of platinum-based anticancer drugs

Targeting and delivery of platinum-based anticancer drugs

The state-of-play and future of platinum drugs

Platinum(IV)-Ferrocene Conjugates and Their Cyclodextrin Host–Guest Complexes

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