Evaluation of Antitumor Effects of Folate-Conjugated Methyl-β-cyclodextrin in Melanoma

Motoyama, Keiichi; Onodera, Risako; Tanaka, Nao; Kameyama, Kazuhisa; Higashi, Taishi; Kariya, Ryusho; Okada, Seiji; Arima, Hisatomi

doi:10.1248/bpb.b14-00531

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…Recently, there has been evidence that a folate-conjugated agent could be involved in the induction of autophagic cell death in melanoma cells. A folate-conjugated methyl-β-cyclodextrin showed cytotoxic effects against FRα-positive melanoma tumor cells through FR-α-mediated endocytosis by eliciting the formation of autophagosomes [44]. Furthermore, encapsulation of vincristine into folic acid-conjugated PEGylated liposomes overcame multidrug resistance to chemotherapy in KBv200 cells [45].…”

Section: Discussionmentioning

confidence: 99%

Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions

Skinner¹,

McMichael²,

Jaime-Ramirez³

et al. 2016

Melanoma Research

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The folate receptor (FR) is over-expressed on the vascular side of cancerous cells including those of the breast, ovaries, testes, and cervix. We hypothesized that a folate-conjugated immunoglobulin (F-IgG) would bind to the FR that is over-expressed on melanoma tumor cells to target these cells for lysis by natural killer (NK) cells. Folate receptor expression was confirmed in the Mel-39 (human melanoma) cell line by flow cytometry and immunoblot analysis, using KB (human oral epithelial) and F01 (human melanoma) as a positive and negative control, respectively. FR-positive and negative cell lines were treated with F-IgG or control immunoglobulin G (C-IgG) in the presence or absence of cytokines in order to determine NK cell ability to lyse FR-positive cell lines. NK cell activation was significantly upregulated and lysis of Mel 39 tumor cells enhanced following treatment with F-IgG, as compared to C-IgG at all effector:target (E:T) ratios (p<0.01). This trend was further enhanced by NK cell stimulation with the activating cytokine interleukin-12 (IL-12). NK cell production of cytokines such as interferon-gamma (IFN-γ), macrophage inflammatory protein 1 alpha (MIP-1α), and regulated on activation normal T-cell expressed and secreted (RANTES) were also significantly increased in response to co-stimulation with IL-12 stimulation and F-IgG-coated Mel 39 target cells, as compared to controls (p<0.01). In contrast, F-IgG did not bind to the FR-negative cell line F01 and had no significant effect on NK cell lysis or cytokine production. This research indicates the potential use of F-IgG for its ability to induce an immune response from NK cells against FR-positive melanoma tumor cells which can be further enhanced by the addition of cytokines.

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Section: Discussionmentioning

confidence: 99%

Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions

Skinner¹,

McMichael²,

Jaime-Ramirez³

et al. 2016

Melanoma Research

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“…Recently, CyDs and their derivatives are expected as APIs against various diseases such as Niemann-Pick disease type C (NPC), [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] Alzheimer's disease, [53][54][55][56][57][58] leukemia, 59) cerebral ischemic injury, 60) chronic renal failure, 61) hyperlipidemia, 62) atherosclerosis, 63) AIDS, 64,65) diabetic kidney disease, 66) influenza, 67) sterility, [68][69][70] peripheral artery disease, 71) bacterial growth, 72) solid cancers, [73][74][75][76][77][78] GM1-gangliosidosis, 79) septic shock, [80][81][82] α-synucleinopathy, 83) hypervitaminosis, 84) and transthyretin-related familial amyloidotic polyneuropathy (FAP).…”

Section: Cyclodextrin-based Molecular Necklace As Antitumor Drugmentioning

confidence: 99%

“…87) We have developed a CyD-based antitumor drug, namely folate appended-methyl-β-CyD (FA-M-β-CyD), thus far. 75,76,78) FA-M-β-CyD induced mitophagy after uptake into folate receptor-overexpressing tumor cells, leading to tumor-selective antitumor activity. 78) More recently, to improve tumor selectivity, blood retention, and safety of FA-M-β-CyD, we newly prepared a molecular necklace (polyrotaxane) consisting of FA-M-β-CyD (Fig.…”

Section: Cyclodextrin-based Molecular Necklace As Antitumor Drugmentioning

confidence: 99%

Cyclodextrin-Based Molecular Accessories for Drug Discovery and Drug Delivery

Higashi

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Recently, active pharmaceutical ingredients (APIs) have been dramatically expanding from low-molecular weight drugs to peptides, proteins, antibodies, genes, oligonucleotides, cells, and machines. Therefore to develop pharmaceutical technologies and drug delivery systems (DDS) for these APIs, advanced molecules and novel concepts are needed. In this review, we introduce cyclodextrin-based supramolecular accessories such as molecular necklace, molecular earring, and intelligent molecular necklace, and describe their application for pharmaceutical technology and DDS. In addition, we also introduce utility of supramolecular accessories as antitumor drugs. Finally, we propose a new concept in pharmaceutical sciences termed as "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences.

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“…Recently, various bioactivities of CyDs have been demonstrated, and CyDs have been used as active pharmaceutical ingredients (APIs) against Niemann-Pick disease type C (NPC), [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76] leukemia, 77) hyperlipidemia, 78) Alzheimer's disease, [79][80][81][82][83][84] cerebral ischemic injury, 85) atherosclerosis, 86) diabetic kidney disease, 87) chronic renal failure, 88) AIDS, 89,90) influenza, 91) peripheral artery disease, 92) sterility, [93][94][95] solid cancers, [96][97][98][99][100][101] bacterial growth, 102) α-synucleinopathy, 103) GM1-gangliosidosis, 104) septic shock, [105][106][107] hypervitaminosis, 108) and transthyretin-related familial amyloidotic polyneuropathy (FAP) …”

Section: Cyclodextrin-based Supramolecular Pharmacology and Drug Discmentioning

confidence: 99%

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

et al. 2018

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Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

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Evaluation of Antitumor Effects of Folate-Conjugated Methyl-β-cyclodextrin in Melanoma

Cited by 19 publications

References 42 publications

Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions

Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions

Cyclodextrin-Based Molecular Accessories for Drug Discovery and Drug Delivery

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

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