Mesoporous Silica Nanoparticle-Based Combination of Niclosamide and Doxorubicin: Effect of Treatment Regimens on Breast Cancer Subtypes

Lohiya, Garima; Katti, Dhirendra S.

doi:10.1021/acsabm.1c00753

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…The results, thereby, provide multiple optimized stoichiometries for NIC + DOX for the BC subtypes, making it prudent to screen these combinations in animal models and at least in terminally ill patients. Furthermore, as the NIC and DOX synergized in multiple stoichiometries, screening the compounds structurally similar to NIC could advance the therapeutic potency [ 198 ]. This could even further moderate the significant DOX extent for an efficient BC treatment.…”

Section: Discussion Of Recent Attempts Using Mesoporous Silica Nanopa...mentioning

confidence: 99%

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

et al. 2023

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Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core–shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size–shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size–shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications.

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Section: Discussion Of Recent Attempts Using Mesoporous Silica Nanopa...mentioning

confidence: 99%

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

et al. 2023

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“…Several molecular targets and pathways have been implicated, including degradation of β-catenin induced upon phosphorylation of glycogen synthase kinase-3 (GSK-3β) [ 80 , 81 , 82 ]. This small molecule can be combined with conventional cytotoxic agents such as camptothecin or temozolomide to treat glioblastoma [ 83 , 84 ], with paclitaxel or doxorubicin to treat triple-negative breast cancer [ 85 , 86 ], and with other drugs used to treat colon cancer, prostate cancer, osteosarcoma, etc. [ 87 , 88 ].…”

Section: Drug Repositioning To Target the Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

“…In brief, NCS is a good candidate for repurposing in oncology, but the active principle should probably be reformulated because it has a poor aqueous solubility and a low bioavailability. The use of cyclodextrin–NCS complexes, polymeric micelles, or specific nanoparticles containing NCS have been proposed to improve the anticancer efficacy of the compound [ 85 , 86 , 99 , 100 ].…”

Section: Drug Repositioning To Target the Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors

Thuru

Magnez

El-Bouazzati

et al. 2022

Cancers

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Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1/PD-L1 checkpoint. Here, we have reviewed several types of drugs known to alter the checkpoint, either directly via the blockade of PD-L1 or indirectly via an action on upstream effectors (such as STAT3) to suppress PD-L1 transcription or to induce its proteasomal degradation. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, and a few other modulators of the PD-1/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.

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“…In the past decade, increasing interest in leveraging niclosamide as an anticancer agent has led to the discovery that niclosamide targets a wide range of pathways such as regulation of Wnt/β-catenin 18,19 , mTORC1 20–22 , STAT3 23–25 , NF-κB 25,26 , and Notch signaling pathways. 27,28 Several literature reports indicate niclosamide’s activity in several cancers such as adrenocortical carcinoma 29 , head and neck cancer 30 , colon cancer 31 , leukemia 32 , lung cancer 33 , glioblastomas 34 , renal cell carcinoma 35 , prostate cancer 36 , ovarian cancer 37 , and breast cancer 38 . Pyrvinium pamoate has also been utilized as an anticancer agent due to its ability to modulate mitochondrial activity.…”

Section: Introductionmentioning

confidence: 99%

Repurposing mitochondrial-targeting anthelmintic agents with GLUT1 inhibitor BAY-876 for cancer therapy

Schumacher,

Iyer,

Rumbley

et al. 2024

Preprint

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Cancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of efficacy in vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors. To test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Here, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested. In this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies warrant further investigation into targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.

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Mesoporous Silica Nanoparticle-Based Combination of Niclosamide and Doxorubicin: Effect of Treatment Regimens on Breast Cancer Subtypes

Cited by 11 publications

References 48 publications

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors

Repurposing mitochondrial-targeting anthelmintic agents with GLUT1 inhibitor BAY-876 for cancer therapy

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