Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond
Abstract
1. Introduction
2. Methodology
3. Breast Cancer
4. Nano-Based Therapeutics: A Paradigm Shift in the Treatment of BC
4.1. Polymeric-Based Nanoparticles
4.2. Liposomal Nanoparticles
4.3. Dendrimer Nanoparticles
4.4. Inorganic Nanoparticles
4.5. Hybrid Nanoparticles
5. Mechanistic Insights of UPR Activation in Breast Cancer Treatment
5.1. ER Stress Response Pathway
5.1.1. PERK Lineage of UPRER Pathway
5.1.2. IRE1 Lineage of UPRER Pathway
5.1.3. ATF6 Lineage of UPRER Pathway
5.2. ER Stress Induced Apoptosis
5.3. ER Stress Induced Autophagy
6. FDA Approved Nanotechnological Formulations for BC
7. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Inhibitor Name | Clinical Implications | Phase | NCT Number |
---|---|---|---|
Epidermal Growth Factor (EGF) receptor inhibitors | |||
Afatinib | Pan-HER tyrosine kinase inhibitor | Phase II | NCT02511847 |
Dasatinib | Pan-Src tyrosine kinase inhibitor | Phase II | NCT02720185 |
Vascular Endothelial Growth Factor (VEGF) receptor inhibitors | |||
Sunitinib | Inhibition of proliferation, invasion, and apoptosis resistance in TNBC cell lines | Phase I/II | NCT00887575 |
Apatinib | Tyrosine kinase inhibitor targetting VEGFR2 | Phase II | NCT01176669 |
Poly ADP-Ribose Polymerase (PARP) inhibitor | |||
Iniparib | Non-competitive PARP inhibitor | Phase II | NCT01045304 |
Veliparib | PARP1/2 inhibitor | Phase II | NCT01306032 |
Fibroblast Growth Factor (FGF) receptor inhibitor | |||
Dovitinib | FGFR, VEGFR and PDGFR inhibitor | Phase II | NCT01528345 |
Lucitanib | FGFR1/2/3 and VEGFR1/2/3 inhibitor | Phase II | NCT02202746 |
Androgen Receptor (AR) inhibitors | |||
Bicalutamide | Androgen antagonist | Phase III | NCT03055312 |
Seviteronel | Cytochrome P450c17a inhibitor | Phase I/II | NCT02580448 |
Formulations of NPs | Model-Type | Remarks | Reference |
---|---|---|---|
Dual peptide-decorated melanin-like NPs | In vitro: breast cancer Hela, and MDA-MB-231 cells In vivo: BALB/c nude mice | Beclin 1 promoted autophagy, but activated minimal in vitro cytotoxicity, sensitized cancer cells to photothermal therapy thereby enhancing significant cell killing, RGD- mediated tumor targeting increased the tumor targeting for well-regulated inhibition of tumor growth at a mild temperature | [117] |
Fe3O4 NPs | In vitro: breast cancer In vivo: mice | Causes ER stress, which includes autophagy and apoptosis Extensive accumulation of autophagosome in the kidney and spleen | [118] |
PAV-AuNPs | In vitro: triple-negative breast cancer cells) MDA-MB-231 cells | Activation of autophagy | [119] |
RQDs | In vitro: endometrium carcinoma JEC cells | Induction of apoptosis and necrosis via, ER stress | [120] |
AANTs-TG-3MA | In vitro: Breast cancer cell MDA-MB-231-TXSA, HFF, and THP-1 cells | AANTs showed good biocompatibility, 3MA, at a non-toxic dose, reduced the autophagy-level, and improved the cell killing effect of AANTs-TG, TG and 3MA in combination enhanced the ER stress signaling | [121] |
AgNP (2 and 15 nm) | In vitro: human MCF-7 and T-47D breast cancer cells | Induced upregulation of the transcription factors ATF-4 and GADD153/CHOP and induction of apoptosis. | [122,123] |
AgNPs (75 nm) | In vitro: human MCF-7 and T-47D breast cancer cells In vivo: TNBC tumor xenografts mice. | MCF-7 and T-47D are more sensitive to MCF-10A cells and Induced ER stress in TNBC cells Effective at non-toxic doses for reducing the growth | [124] |
AgNPs-EPSae (AgNPs-specific polysaccharide) | In vitro: human breast (SKBR3 and 8701-BC) | ER stress, oxidative stress and mitochondrial impairment triggering cell death trough apoptosis and/or autophagy activation. | [125] |
AgNPs-EPSae (AgNPs-specific polysaccharide) | In vitro: human breast (SKBR3 and 8701-BC) | ER stress, oxidative stress, and mitochondrial impairment triggering cell death trough apoptosis and/or autophagy activation. | [125] |
PLGA NPs loaded with LY294002 | In vitro: lungs cancer cells H157, H460, H1650 In vivo: Xenograft animal model (female athymic nude mice) | Accumulation and pronounced induction of ER stress, activation of JNK and prominent in vivo antitumor effect | [126] |
FTIC labeled-PEI-PLGA-PTX-MNPs | In vitro: human brain glioblastoma U251 cells | NPs effectively endocytosed by targeted U251 cells, induction of cell apoptosis, and autophagy | [127] |
PEG-PE micelles | In vitro: A549 lungs cancer cells | Accumulation and induction of ER stress via disturbing ER lipid homeostasis, high expression of CHOP, and proapoptotic Bax/Bak in cancer cells | [128] |
PEGylated nanogels containing AuNPs | In vitro: SCCVII (murine) or A549 (human lung) cells | Enhance cell radiosensitivity, activation of ER stress, JNK activation, and induction of apoptosis, | [129] |
LP-SeNPs | In vitro: human liver carcinoma HepG2 cells | Inhibition of autophagy and activation of mitochondria pathway for the induction of apoptosis | [130] |
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Rahman, S.; Kumar, V.; Kumar, A.; Abdullah, T.S.; Rather, I.A.; Jan, A.T. Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond. Biomedicines 2021, 9, 635. https://doi.org/10.3390/biomedicines9060635
Rahman S, Kumar V, Kumar A, Abdullah TS, Rather IA, Jan AT. Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond. Biomedicines. 2021; 9(6):635. https://doi.org/10.3390/biomedicines9060635
Chicago/Turabian StyleRahman, Safikur, Vijay Kumar, Anuj Kumar, Tasduq S. Abdullah, Irfan A. Rather, and Arif Tasleem Jan. 2021. "Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond" Biomedicines 9, no. 6: 635. https://doi.org/10.3390/biomedicines9060635
APA StyleRahman, S., Kumar, V., Kumar, A., Abdullah, T. S., Rather, I. A., & Jan, A. T. (2021). Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond. Biomedicines, 9(6), 635. https://doi.org/10.3390/biomedicines9060635