Creation of Pure Nanodrugs and Their Anticancer Properties

Kasai, Hitoshi; Murakami, Tatsuya; Ikuta, Yoshikazu; Koseki, Yoshitaka; Baba, Koichi; Oikawa, Hidetoshi; Nakanishi, Hachiro; Okada, Masahiro; Shoji, Mitsuru; Ueda, Minoru; Imahori, Hiroshi; Hashida, Mitsuru

doi:10.1002/anie.201204596

Cited by 153 publications

(127 citation statements)

References 23 publications

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“…14–18 In addition, many types of organic nanoparticles have the advantage of ease of tunability which allows potential applications in varied fields such as optoelectronics, bioimaging, and optical data storage. 17,19–23 The high load of fluorophores in molecular assemblies within nanoparticles is one property that makes them particularly attractive for biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Tunable Cytotoxicity of Rhodamine 6G via Anion Variations

Magut

Das

Fernand³

et al. 2013

J. Am. Chem. Soc.

110

108

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Chemotherapeutic agents with low toxicity to normal tissues are a major goal in cancer research. In this regard, the therapeutic activities of cationic dyes, such as rhodamine 6G, toward cancer cells have been studied for decades with observed toxicities toward normal and cancer cells. Herein, we report rhodamine 6G-based organic salts with varying counter-anions that are stable under physiological conditions, display excellent fluorescence photostability, and more importantly have tunable chemotherapeutic properties. Our in-vitro studies indicate that the hydrophobic compounds of this series allow production of nanoparticles which are non-toxic to normal cells and toxic to cancer cells. Furthermore, the anions, in combination with cations such as sodium, were observed to be non-toxic to both normal and cancer cells. To the best of our knowledge, this is the first demonstration that both the cation and anion play an extremely important and cooperative role in the antitumor properties of these compounds.

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Section: Introductionmentioning

confidence: 99%

Tunable Cytotoxicity of Rhodamine 6G via Anion Variations

Magut

Das

Fernand³

et al. 2013

J. Am. Chem. Soc.

110

108

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“…However, physical encapsulation of this molecule into amphiphilic polymeric NPs is a challenge due to the unfavorable physicochemical properties of the drug, which are attributed to the intrinsically planar structure and moderate polarity of this molecule. [9] Thus, a sophisticated strategy is needed to adapt this potent agent for incorporation into a favorable polymeric delivery platform. We noticed that the phenolate moiety (10-OH) on SN-38 may account for its poor compatibility with polymeric NPs.…”

mentioning

confidence: 99%

“…b) Structures of a small library of SN-38 prodrugs. A variety of hydrophobic moieties were conjugated to the 10-hydroxy group through the formation of phenyl ether (1) or ester (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) bonds. c) Assessment of the stability of the prodrug-encapsulated, self-assembled PEG-PLA nanoparticles (PEG-PLA/prodrug weight ratios fixed at 20:1).…”

mentioning

confidence: 99%

Structure‐Based Rational Design of Prodrugs To Enable Their Combination with Polymeric Nanoparticle Delivery Platforms for Enhanced Antitumor Efficacy

Wang

Xie

et al. 2014

Angewandte Chemie

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Drug-loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN-38 (7-ethyl-10-hydroxycamptothecin)-derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine-tuned the polarity of the SN-38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self-assembly into biodegradable poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-PLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre-eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality.

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“…HepG2 cells were purchased from RIKEN Cell Bank. Following the method of (Kasai et al, 2012), the HepG2 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS), 30 U/mL penicillin, and 30 µg/mL streptomycin under 5% CO 2 at 37°C. HepG2 cells were seeded in 96-well plates (2 × 10 4 cells/well) and incubated for 24 hours.…”

Section: Introductionmentioning

confidence: 99%