177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study

Pirooznia, Nazanin; Abdi, Khosrou; Beiki, Davood; Emami, Farshad; Arab, Seyed Shahriar; Sabzevari, Omid; Soltani-Gooshkhaneh, Samira

doi:10.1016/j.bioorg.2020.104100

Cited by 19 publications

(12 citation statements)

References 43 publications

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“…The cytotoxicity of RGD-SS-CA ( 2 ), RGD-VC-CA ( 3 ), and 1a against the human breast cancer cell line BT549 and the human non-small-cell lung cancer cell line A549 was investigated using a standard CCK-8 cell viability assay. Both of the cell lines are integrin α v β 3 positive. , In our previous study, 1a exhibited high inhibitory activities (in the nanomolar range) against a number of cancer cell lines. The cytotoxicity of 1a is no different between the two cell lines with the IC 50 values of 18.0 ± 8.0 nM in BT549 cells and 19.1 ± 8.7 nM in A549 cells after 48 h incubation (Table ).…”

Section: Resultsmentioning

confidence: 80%

“…Both of the cell lines are integrin α v β 3 positive. 34,35 In our previous study, 1a exhibited high inhibitory activities (in the nanomolar range) against a number of cancer cell lines. The cytotoxicity of 1a is no different between the two cell lines with the IC 50 values of 18.0 ± 8.0 nM in BT549 cells and 19.1 ± 8.7 nM in A549 cells after 48 h incubation (Table 1).…”

Section: ■ Results and Discussionmentioning

confidence: 92%

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Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy

Cheng

et al. 2021

J. Med. Chem.

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Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide−drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

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Section: Resultsmentioning

confidence: 80%

Section: ■ Results and Discussionmentioning

confidence: 92%

Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy

Cheng

et al. 2021

J. Med. Chem.

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“…There is not much research to date on the dosimetry or radiotoxicity of 177 Lu-radiolabeled nanoparticles in small animal models. However, widely varying doses ranging from 6 to 55.5 MBq of 177 Lu-radiolabeled peptides and antibodies have been used in therapeutic studies for mice, [58][59][60][61] which could be used as a starting point for the estimation of safe radioactive doses in the treatment plan. Naturally, the clearance patterns and rates for peptides and antibodies are considerably different from nanomaterials, and the role of the spleen as a dose-limiting organ in this experimental setup cannot be overlooked.…”

Section: Ex Vivo Biodistribution and Dosimetrymentioning

confidence: 99%

A Theranostic Cellulose Nanocrystal‐Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma

Imlimthan

Khng

Keinänen

et al. 2021

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Metastatic melanoma can be difficult to detect until at the advanced state that decreases the survival rate of patients. Several FDA‐approved BRAF inhibitors have been used for treatment of metastatic melanoma, but overall therapeutic efficacy has been limited. Lutetium‐177 (177Lu) enables simultaneous tracking of tracer accumulation with single‐photon emission computed tomography and radiotherapy. Therefore, the codelivery of 177Lu alongside chemotherapeutic agents using nanoparticles (NPs) might improve the therapeutic outcome in metastatic melanoma. Cellulose nanocrystals (CNC NPs) can particularly deliver payloads to lung capillaries in vivo. Herein, 177Lu‐labeled CNC NPs loaded with vemurafenib ([177Lu]Lu‐CNC‐V NPs) is developed and the therapeutic effect in BRAF V600E mutation‐harboring YUMM1.G1 murine model of lung metastatic melanoma is investigated. The [177Lu]Lu‐CNC‐V NPs demonstrate favorable radiolabel stability, drug release profile, cellular uptake, and cell growth inhibition in vitro. In vivo biodistribution reveals significant retention of the [177Lu]Lu‐CNC‐V NPs in the lung, liver, and spleen. Ultimately, the median survival time of animals is doubly increased after treatment with [177Lu]Lu‐CNC‐V NPs compared to control groups. The enhanced therapeutic efficacy of [177Lu]Lu‐CNC‐V NPs in the lung metastatic melanoma animal model provides convincing evidence for the potential of clinical translation for theranostic CNC NP‐based drug delivery systems after intravenous administration.

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“…As integrin-recognition ligands, cyclic pentapeptides containing Arg-Gly-Asp sequence (cyclic RGDyK or cyclic RGDfK) have high affinity toward α V β 3 integrin while maintaining selectivity over the other integrins, such as α V β 5 , α v β 6 and α 5 β 1 . , In this work, cyclic RGDyK (cRGD) with high stability and hydrophilicity was selected to conjugate with biotin to form Biotin-RGD (Figure A). The human non-small cell lung cancer cells, A549, with high expression level of integrins were cultured with Biotin-RGD and NAP-650 for 20 h in the absence or presence of the lysosome inhibitor, chloroquine (CQ), and Biotin-Azide was used as a negative control. Compared with Biotin-Azide, coincubation with Biotin-RGD significantly increased the cellular uptake of NAP-650, while inhibition of the lysosomal proteolytic activity with CQ led to the highest accumulation of NAP-650 in cells (Figure B).…”

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confidence: 99%

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation

Zheng

et al. 2022

J. Am. Chem. Soc.

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As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both in vitro and in vivo, the IFLD strategy expands the toolbox for regulation of secreted and membrane-associated proteins and thus has great potential to be applied in chemical biology and drug discovery.

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177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study

Cited by 19 publications

References 43 publications

Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy

Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy

A Theranostic Cellulose Nanocrystal‐Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation

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