Novel estradiol based metal complexes of Tc-99m

Neto, Carina; Oliveira, Maria Cristina; Gano, Lurdes; Marques, Fernanda; Thiemann, Thies; Santos, Isabel

doi:10.1016/j.jinorgbio.2012.03.001

Cited by 20 publications

(11 citation statements)

References 39 publications

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“…Therefore, an estrogen derivative, 17α-ethynylestradiol (EE2) was chosen as targeting ligand due to its high specificity towards ER+, and its synthetic accessibility. The chemical substitution at the ethynyl position of EE2 is well documented for its retained bioactivity [ 32 , 38 , 39 ]. Thus, chemical modification was performed at the ethynyl position of EE2 for covalent functionalization on particles surface using a heterofunctional PEG as a linker.…”

Section: Discussionmentioning

confidence: 99%

“…The chemical substitution at the ethynyl position of 17α-ethynylestradiol (EE2) is well documented for its retained bioactivity [ 32 , 38 , 39 ]. Thus, amine functionality at the ethynyl position of EE2 was introduced by Sonogashira coupling with 4-bromoaniline to obtain ESTAm and characterized using NMR, HRMS and FTIR (Additional file 1 : Figures S1–S3).…”

Section: Methodsmentioning

confidence: 99%

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Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer

Chauhan¹,

Hernández-Meza²,

Rodríguez-Hernández³

et al. 2018

J Nanobiotechnol

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BackgroundTamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response.ResultsHere we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells.ConclusionsThis work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0345-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer

Chauhan¹,

Hernández-Meza²,

Rodríguez-Hernández³

et al. 2018

J Nanobiotechnol

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“…The ERα competitive binding experiment was performed according to the previous procedure . The reaction mixture containing different concentration of ligands (50 μL) in the ERα binding buffer [prepared from dithiotheitol (2 mM), glycerol (10%), Tris-HCl (pH 7.5, 10 mM) and BSA (1 mg/mL) was treated with 3 H-Estradiol ( 3 H-ES, 23.8 nM) and ERα protein solution (0.25 pmol) (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…The clinical outcomes of 18 F-FES are encouraging, but the availability and accessibility of the cyclotron based source ( 18 F) are still an issue in many medical centers. Therefore, a dedicated attempt is being made toward the development of estradiol based tracers labeled with technitium-99m ( 99m Tc) due to its ideal nuclear decay properties, easy accessibility, low isotope cost, and simple and rich chelating chemistry. ,− However, many of the complexes displayed suboptimal in vivo target selectivity due to the high lipophilicity or very fast metabolism. Apparently, there is a pressing requirement of facile chemical strategies that can provide cost-effective imaging of breast tumor with clinical translation potential.…”

Section: Introductionmentioning

confidence: 99%

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

et al. 2016

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The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc-(EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/μmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 μM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERβ and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy.

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“…99 Novel estradiol based metal complexes of 99m Tc were also reported as imaging agents for estrogen receptor (ER) positive breast tumours. 6 17 Ruthenium…”

Section: Annual Reports a Reviewmentioning

confidence: 99%

Inorganic pharmaceuticals

Holder

2013

Annu. Rep. Prog. Chem., Sect. A: Inorg. Chem.

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This chapter reviews the literature reported during 2012 on some important advances in the area of inorganic pharmaceuticals. Research highlights for the respective metals during the year are also given. Highlights(I) A titanium(IV) which was highly toxic towards HeLa S3 and Hep G2 cancer cell lines, 1 (II) pharmacological studies of [bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxovanadium(IV)], [VO(dmpp) 2 ] with fatty Zucker rats, 2 (III) the first X-ray crystal structures of nickel(II) and copper(II) salphen metal complexes bound to a quadruplex DNA, 3 (IV) evaluation of copper(II) complexes with thiosemicarbazone ligands as anti-cancer agents on human colon cancer and human breast cancer cell lines, 4 (V) the first report of ZnO nanoflowers that show significant proangiogenic properties as observed by in vitro and in vivo angiogenesis assays, 5 (VI) novel estradiol based metal complexes of 99m Tc as imaging agents for estrogen receptor (ER) positive breast tumours, 6 (VII) the use of [Ru(phen) 2 dppz] 2+ to study aggregation of a-synuclein (aS), which is associated with the development of Parkinson's disease, 7 and (VIII) the real-time monitoring of the caspase cascade in cancer cells during apoptosis with various caspase substrate-linked fluorescent proteins-conjugated gold nanoparticles as a new imaging probe.

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Novel estradiol based metal complexes of Tc-99m

Cited by 20 publications

References 39 publications

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

Inorganic pharmaceuticals

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