Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs

Dubowchik, Gene M.; Walker, Michael

doi:10.1016/s0163-7258(99)00018-2

Cited by 259 publications

(240 citation statements)

References 464 publications

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“…Because of elevated expression of FR on various types of tumor cells and activated macrophages, folic acid has been exploited extensively as a drug delivery vehicle for cancer and inflammatory diseases (25)(26)(27)(28)(29). Because higher potencies are achieved generally when the drug is released from its attached targeting ligand (i.e., folic acid) in an unaltered form (30)(31)(32)(33), the data presented here suggest that disulfide bridges between folate and its therapeutic payload might constitute suitable linkers for site-specific drug release. This argument is supported by the much more potent antitumor activity of a disulfide-linked folate-mitomycin C conjugate relative to an analogus amide-linked conjugate (34,35).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging

Yang¹,

Chen

Vlahov

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

290

244

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Despite functional evidence for disulfide bond-reducing activity in endosomal compartments, the mechanistic details pertaining to such process (e.g., kinetics and sites of disulfide reduction) remain largely controversial. To address these questions directly, we have synthesized a previously uncharacterized fluorescent folate conjugate, folate-(BODIPY FL)-SS-rhodamine (folate-FRET), that changes fluorescence from red to green upon disulfide bond reduction. Using this construct, we have observed that disulfide reduction: (i) occurs with a half-time of 6 h after folate-FRET endocytosis, (ii) begins in endosomes and does not depend significantly on redox machinery located on the cell surface or within the lysosome or the Golgi apparatus, (iii) occurs independently of endocytic vesicle trafficking along microtubules, and (iv) yields products that are subsequently sorted into distinct endosomes and trafficked in different directions. Finally, colocalization of folate and transferrin receptors suggest that conclusions derived from this study may apply to other endocytic pathways.disulfide bond reduction ͉ endosome ͉ folate receptor ͉ drug targeting

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Section: Discussionmentioning

confidence: 99%

Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging

Yang¹,

Chen

Vlahov

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

290

244

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“…These protocols are designed, for instance, to test novel marker proteins, 1 perform gene replacement and/or augmentation trials, 2 test prodrug activation, 3 evaluate cell-based therapies 4 and investigate oncolytic viruses. 5 During the last 5 years of vector and transgene development, it has become apparent that insufficient delivery of genetic material to tumor cells in vivo and low and/or transient gene expression are the main limitations to the effectiveness of this new treatment paradigm.…”

Section: Introductionmentioning

confidence: 99%

Quantitation of HSV mass distribution in a rodent brain tumor model

Schellingerhout¹,

Rainov

Breakefield

et al. 2000

Gene Ther

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A number of different viral vectors have been used for gene therapy of tumors, with many more under construction, ultimately designed to improve tumor targeting and transduction efficiency. It has become apparent that insufficient viral delivery can be a key limitation to treatment efficacy. We have studied the in vivo mass distribution of a herpes simplex virus type 1 (HSV) vector, hrR3, by radiolabeling it with 111 In-oxine. The virus was administered to intracerebral 9L glioma bearing Fisher (F-344) rats by intracarotid and intratumoral injection. The blood half-life of the virus was 1 min (fast component, 10% contribution) and 180 min (slow component, 90% contribution). Approximately 20% of activity had been excreted by 24 h. With intracarotid injection, the total amount of virus that accumulated in tumor was 0.10 ± 0.07% of the injected dose (ID)/g at 1 h and 0.19 ± 0.01% ID/g at 24 h. By comparison, co-injection of RMP-7,

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“…Substitution of Ala for VIP amino acids at positions 3, 5, 7, 10, 15, 20 or 21 reduced binding affinity to VPAC 1 -R by over 1-order of magnitude [19,36]. The analog (Ala 2,8,9,11,19,24,25,27,28 )VIP is a potent VPAC 1 -R agonist that is resistant to degradation [20].…”

Section: Discussionmentioning

confidence: 99%

“…(A-NL-K)VIP, which is an analog of the selective VPAC 1 -R agonist, (Ala 2,8,9,11,19,24,25,27,28 )VIP, was synthesized using solid phase techniques. The VIP-CPT conjugates were synthesized by coupling the CPT to the Lys 28 of (A-NL-K)VIP-L2 as described previously [19].…”

Section: Preparation Of Peptidesmentioning

confidence: 99%

“…(Ala 2,8,9,19,24.25.27 , Nle 17 , Lys 28 )VIP, (A-NL-K)VIP, was synthesized and Lys 28 was coupled to a linker, N-methyl-aminoethyl-glycine, L2, which formed a carbamate bond with CPT. The resulting (A-NL-K)VIP-L2-CPT was cytotoxic for MCF7 breast cancer cells, which have VPAC 1 -R, with IC 50 values of 380 and 90 nM using the MTT and clonogenic assays, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Vasoactive intestinal peptide–camptothecin conjugates inhibit the proliferation of breast cancer cells

et al. 2007

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The effects of vasoactive intestinal peptide camptothecin (VIP-CPT) conjugates were investigated on breast cancer cells and cells transfected with VIP receptors (R). (Ala 2,8,9,19,24.25.27 , Nle 17 , Lys 28 )VIP, (A-NL-K)VIP, was synthesized and Lys 28 was coupled to a linker, N-methyl-aminoethyl-glycine, L2, which formed a carbamate bond with CPT. The resulting (A-NL-K)VIP-L2-CPT was cytotoxic for MCF7 breast cancer cells, which have VPAC 1 -R, with IC 50 values of 380 and 90 nM using the MTT and clonogenic assays, respectively.

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Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs

Cited by 259 publications

References 464 publications

Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging

Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging

Quantitation of HSV mass distribution in a rodent brain tumor model

Vasoactive intestinal peptide–camptothecin conjugates inhibit the proliferation of breast cancer cells

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