Nanotechnology-Based Targeting of MTOR Signaling in Cancer

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Aug 22

PMID 32821100

Citations 4

Authors

Mee-Sup Yoon

Affiliations

Soon will be listed here.

Abstract

Mammalian target of rapamycin (mTOR) is a master regulator of cell growth and metabolism, which is activated in response to intra- and extracellular signals, including nutrients, growth factors, and cellular energy levels. The frequent dysregulation of mTOR signaling in cancer makes it an attractive therapeutic target, and several types of mTOR inhibitors have been developed. Nanoparticle-based mTOR modulators are predicted to target various cancers and deliver as well as release drugs in a controlled manner, resulting in enhanced bioavailability and reduced side effects. This mini-review is focused on the molecular mechanism of nanoparticle-based mTOR modulator action as well as the current development of mTOR inhibitors using nanoparticles. Understanding the biological function of nanoparticle-based mTOR modulators will contribute to the development of efficient nano-therapeutics for the treatment of cancers.

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References

Polak P, Hall M . mTORC2 Caught in a SINful Akt. Dev Cell. 2006; 11(4):433-4. DOI: 10.1016/j.devcel.2006.09.005. View

Khanna N, Fang Y, Yoon M, Chen J . XPLN is an endogenous inhibitor of mTORC2. Proc Natl Acad Sci U S A. 2013; 110(40):15979-84. PMC: 3791717. DOI: 10.1073/pnas.1310434110. View

Haydon M, Googe J, Sorrells D, Ghali G, Li B . Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck. Cancer. 2000; 88(12):2803-10. DOI: 10.1002/1097-0142(20000615)88:12<2803::aid-cncr20>3.0.co;2-5. View

Champion J, Mitragotri S . Shape induced inhibition of phagocytosis of polymer particles. Pharm Res. 2008; 26(1):244-9. PMC: 2810499. DOI: 10.1007/s11095-008-9626-z. View

He C, Hu Y, Yin L, Tang C, Yin C . Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. 2010; 31(13):3657-66. DOI: 10.1016/j.biomaterials.2010.01.065. View

Halas N . Nanoscience under glass: the versatile chemistry of silica nanostructures. ACS Nano. 2009; 2(2):179-83. DOI: 10.1021/nn800052e. View

Lehenkari P, Kellinsalmi M, Napankangas J, Ylitalo K, Monkkonen J, Rogers M . Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002; 61(5):1255-62. DOI: 10.1124/mol.61.5.1255. View

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

Kim S, Kim S, Klempner S, Yoon J, Kim N, Ahn S . Rapamycin-insensitive companion of mTOR (RICTOR) amplification defines a subset of advanced gastric cancer and is sensitive to AZD2014-mediated mTORC1/2 inhibition. Ann Oncol. 2016; 28(3):547-554. DOI: 10.1093/annonc/mdw669. View

10.

Lastwika K, Wilson 3rd W, Li Q, Norris J, Xu H, Ghazarian S . Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer. Cancer Res. 2015; 76(2):227-38. DOI: 10.1158/0008-5472.CAN-14-3362. View

11.

Gkountakos A, Pilotto S, Mafficini A, Vicentini C, Simbolo M, Milella M . Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex. Carcinogenesis. 2018; 39(8):971-980. DOI: 10.1093/carcin/bgy086. View

12.

Chiu H, Xia T, Lee Y, Chen C, Tsai J, Wang Y . Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress. Nanoscale. 2014; 7(2):736-46. DOI: 10.1039/c4nr05509h. View

13.

Bezerra D, Castro F, Alves A, Pessoa C, Moraes M, Silveira E . In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper. Braz J Med Biol Res. 2006; 39(6):801-7. DOI: 10.1590/s0100-879x2006000600014. View

14.

Roczniak-Ferguson A, Petit C, Froehlich F, Qian S, Ky J, Angarola B . The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012; 5(228):ra42. PMC: 3437338. DOI: 10.1126/scisignal.2002790. View

15.

Oza A, Elit L, Tsao M, Kamel-Reid S, Biagi J, Provencher D . Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011; 29(24):3278-85. PMC: 3158598. DOI: 10.1200/JCO.2010.34.1578. View

16.

Bertoli F, Garry D, Monopoli M, Salvati A, Dawson K . The Intracellular Destiny of the Protein Corona: A Study on its Cellular Internalization and Evolution. ACS Nano. 2016; 10(11):10471-10479. DOI: 10.1021/acsnano.6b06411. View

17.

Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas P . Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998; 64(4):353-6. DOI: 10.1055/s-2006-957450. View

18.

Xia T, Kovochich M, Liong M, Zink J, Nel A . Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano. 2009; 2(1):85-96. DOI: 10.1021/nn700256c. View

19.

Han J, Jeong S, Park M, Kim G, Kwon N, Kim H . Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012; 149(2):410-24. DOI: 10.1016/j.cell.2012.02.044. View

20.

Stern S, Adiseshaiah P, Crist R . Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Part Fibre Toxicol. 2012; 9:20. PMC: 3441384. DOI: 10.1186/1743-8977-9-20. View