Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Allemailem, Khaled S, Almatroudi, Ahmad, Alrumaihi, Faris, Almatroodi, Saleh A, Alkurbi, Mohammad O, Basfar, Ghaiyda Talal, Rahmani, Arshad Husain, Khan, Amjad Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324981/
https://www.ncbi.nlm.nih.gov/pubmed/34345172
http://dx.doi.org/10.2147/IJN.S321343
_version_ 1783731476593901568
author Allemailem, Khaled S
Almatroudi, Ahmad
Alrumaihi, Faris
Almatroodi, Saleh A
Alkurbi, Mohammad O
Basfar, Ghaiyda Talal
Rahmani, Arshad Husain
Khan, Amjad Ali
author_facet Allemailem, Khaled S
Almatroudi, Ahmad
Alrumaihi, Faris
Almatroodi, Saleh A
Alkurbi, Mohammad O
Basfar, Ghaiyda Talal
Rahmani, Arshad Husain
Khan, Amjad Ali
author_sort Allemailem, Khaled S
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8324981
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-83249812021-08-02 Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics Allemailem, Khaled S Almatroudi, Ahmad Alrumaihi, Faris Almatroodi, Saleh A Alkurbi, Mohammad O Basfar, Ghaiyda Talal Rahmani, Arshad Husain Khan, Amjad Ali Int J Nanomedicine Review 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. Dove 2021-07-26 /pmc/articles/PMC8324981/ /pubmed/34345172 http://dx.doi.org/10.2147/IJN.S321343 Text en © 2021 Allemailem et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Allemailem, Khaled S
Almatroudi, Ahmad
Alrumaihi, Faris
Almatroodi, Saleh A
Alkurbi, Mohammad O
Basfar, Ghaiyda Talal
Rahmani, Arshad Husain
Khan, Amjad Ali
Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics
title 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_short 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
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324981/
https://www.ncbi.nlm.nih.gov/pubmed/34345172
http://dx.doi.org/10.2147/IJN.S321343
work_keys_str_mv AT allemailemkhaleds novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT almatroudiahmad novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT alrumaihifaris novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT almatroodisaleha novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT alkurbimohammado novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT basfarghaiydatalal novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT rahmaniarshadhusain novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics
AT khanamjadali novelapproachesofdysregulatinglysosomefunctionsincancercellsbyspecificdrugsanditsnanoformulationsasmartapproachofmoderntherapeutics