Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics

Khaled S Allemailem,1,2 Ahmad Almatroudi,1 Faris Alrumaihi,1 Saleh A Almatroodi,1 Mohammad O Alkurbi,3 Ghaiyda Talal Basfar,3 Arshad Husain Rahmani,1 Amjad Ali Khan2 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Ba...

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Autores principales:	Allemailem KS, Almatroudi A, Alrumaihi F, Almatroodi SA, Alkurbi MO, Basfar GT, Rahmani AH, Khan AA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	lysosome cancer lysosomotropic agents nanoparticles lysosome drug targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f4246eea46a749f7a2b032b170ca0671
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spelling	oai:doaj.org-article:f4246eea46a749f7a2b032b170ca06712021-12-02T16:17:35ZNovel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics1178-2013https://doaj.org/article/f4246eea46a749f7a2b032b170ca06712021-07-01T00:00:00Zhttps://www.dovepress.com/novel-approaches-of-dysregulating-lysosome-functions-in-cancer-cells-b-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Khaled S Allemailem,1,2 Ahmad Almatroudi,1 Faris Alrumaihi,1 Saleh A Almatroodi,1 Mohammad O Alkurbi,3 Ghaiyda Talal Basfar,3 Arshad Husain Rahmani,1 Amjad Ali Khan2 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 3Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Amjad Ali KhanDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6699, Buraydah, 51452, Saudi ArabiaTel +966-16-3800050 Ext. 15445Fax +96616 3801628Email akhan@qu.edu.saAbstract: The smart strategy of cancer cells to bypass the caspase-dependent apoptotic pathway has led to the discovery of novel anti-cancer approaches including the targeting of lysosomes. Recent discoveries observed that lysosomes perform far beyond just recycling of cellular waste, as these organelles are metabolically very active and mediate several signalling pathways to sense the cellular metabolic status. These organelles also play a significant role in mediating the immune system functions. Thus, direct or indirect lysosome-targeting with different drugs can be considered a novel therapeutic approach in different disease including cancer. Recently, some anticancer lysosomotropic drugs (eg, nortriptyline, siramesine, desipramine) and their nanoformulations have been engineered to specifically accumulate within these organelles. These drugs can enhance lysosome membrane permeabilization (LMP) or disrupt the activity of resident enzymes and protein complexes, like v-ATPase and mTORC1. Other anticancer drugs like doxorubicin, quinacrine, chloroquine and DQ661 have also been used which act through multi-target points. In addition, autophagy inhibitors, ferroptosis inducers and fluorescent probes have also been used as novel theranostic agents. Several lysosome-specific drug nanoformulations like mixed charge and peptide conjugated gold nanoparticles (AuNPs), Au-ZnO hybrid NPs, TPP-PEG-biotin NPs, octadecyl-rhodamine-B and cationic liposomes, etc. have been synthesized by diverse methods. These nanoformulations can target cathepsins, glucose-regulated protein 78, or other lysosome specific proteins in different cancers. The specific targeting of cancer cell lysosomes with drug nanoformulations is quite recent and faces tremendous challenges like toxicity concerns to normal tissues, which may be resolved in future research. The anticancer applications of these nanoformulations have led them up to various stages of clinical trials. Here in this review article, we present the recent updates about the lysosome ultrastructure, its cross-talk with other organelles, and the novel strategies of targeting this organelle in tumor cells as a recent innovative approach of cancer management.Keywords: lysosome, cancer, lysosomotropic agents, nanoparticles, lysosome drug targetingAllemailem KSAlmatroudi AAlrumaihi FAlmatroodi SAAlkurbi MOBasfar GTRahmani AHKhan AADove Medical Pressarticlelysosomecancerlysosomotropic agentsnanoparticleslysosome drug targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5065-5098 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lysosome cancer lysosomotropic agents nanoparticles lysosome drug targeting Medicine (General) R5-920
spellingShingle	lysosome cancer lysosomotropic agents nanoparticles lysosome drug targeting Medicine (General) R5-920 Allemailem KS Almatroudi A Alrumaihi F Almatroodi SA Alkurbi MO Basfar GT Rahmani AH Khan AA Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
description	Khaled S Allemailem,1,2 Ahmad Almatroudi,1 Faris Alrumaihi,1 Saleh A Almatroodi,1 Mohammad O Alkurbi,3 Ghaiyda Talal Basfar,3 Arshad Husain Rahmani,1 Amjad Ali Khan2 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 2Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia; 3Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Amjad Ali KhanDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6699, Buraydah, 51452, Saudi ArabiaTel +966-16-3800050 Ext. 15445Fax +96616 3801628Email akhan@qu.edu.saAbstract: The smart strategy of cancer cells to bypass the caspase-dependent apoptotic pathway has led to the discovery of novel anti-cancer approaches including the targeting of lysosomes. Recent discoveries observed that lysosomes perform far beyond just recycling of cellular waste, as these organelles are metabolically very active and mediate several signalling pathways to sense the cellular metabolic status. These organelles also play a significant role in mediating the immune system functions. Thus, direct or indirect lysosome-targeting with different drugs can be considered a novel therapeutic approach in different disease including cancer. Recently, some anticancer lysosomotropic drugs (eg, nortriptyline, siramesine, desipramine) and their nanoformulations have been engineered to specifically accumulate within these organelles. These drugs can enhance lysosome membrane permeabilization (LMP) or disrupt the activity of resident enzymes and protein complexes, like v-ATPase and mTORC1. Other anticancer drugs like doxorubicin, quinacrine, chloroquine and DQ661 have also been used which act through multi-target points. In addition, autophagy inhibitors, ferroptosis inducers and fluorescent probes have also been used as novel theranostic agents. Several lysosome-specific drug nanoformulations like mixed charge and peptide conjugated gold nanoparticles (AuNPs), Au-ZnO hybrid NPs, TPP-PEG-biotin NPs, octadecyl-rhodamine-B and cationic liposomes, etc. have been synthesized by diverse methods. These nanoformulations can target cathepsins, glucose-regulated protein 78, or other lysosome specific proteins in different cancers. The specific targeting of cancer cell lysosomes with drug nanoformulations is quite recent and faces tremendous challenges like toxicity concerns to normal tissues, which may be resolved in future research. The anticancer applications of these nanoformulations have led them up to various stages of clinical trials. Here in this review article, we present the recent updates about the lysosome ultrastructure, its cross-talk with other organelles, and the novel strategies of targeting this organelle in tumor cells as a recent innovative approach of cancer management.Keywords: lysosome, cancer, lysosomotropic agents, nanoparticles, lysosome drug targeting
format	article
author	Allemailem KS Almatroudi A Alrumaihi F Almatroodi SA Alkurbi MO Basfar GT Rahmani AH Khan AA
author_facet	Allemailem KS Almatroudi A Alrumaihi F Almatroodi SA Alkurbi MO Basfar GT Rahmani AH Khan AA
author_sort	Allemailem KS
title	Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title_short	Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title_full	Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title_fullStr	Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title_full_unstemmed	Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title_sort	novel approaches of dysregulating lysosome functions in cancer cells by specific drugs and its nanoformulations: a smart approach of modern therapeutics
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/f4246eea46a749f7a2b032b170ca0671
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Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics

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