Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics

Subhan, Abdus

doi:10.1039/d2ra02005j

Cited by 16 publications

(9 citation statements)

References 201 publications

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“…Nanocarriers, including liposomes, ,– metal/metal oxide nanoparticles, – polymer nanoparticles, – and nanosized metal–organic frameworks, – are usually relatively large, with diameters spanning tens of nanometers. As a result, nanocarriers are typically unable to cross membranes, and they are generally internalized into cells by endocytic uptake mechanisms. , Notably, this is the case for other reported PCCs.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Cell Entry Mechanism, Disassembly, and Toxicity of the Nanocage PCC-1: Insights into Its Potential as a Drug Delivery Vehicle

Xiao,

Lin,

Drake

et al. 2023

J. Am. Chem. Soc.

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The porous coordination cage PCC-1 represents a new platform potentially useful for the cellular delivery of drugs with poor cell permeability and solubility. PCC-1 is a metal−organic polyhedron constructed from zinc metal ions and organic ligands through coordination bonds. PCC-1 possesses an internal cavity that is suitable for drug encapsulation. To better understand the biocompatibility of PCC-1 with human cells, the cell entry mechanism, disassembly, and toxicity of the nanocage were investigated. PCC-1 localizes in the nuclei and cytoplasm within minutes upon incubation with cells, independent of endocytosis and cargo, suggesting direct plasma membrane translocation of the nanocage carrying its guest in its internal cavity. Furthermore, the rates of cell entry correlate to extracellular concentrations, indicating that PCC-1 is likely diffusing passively through the membrane despite its relatively large size. Once inside cells, PCC-1 disintegrates into zinc metal ions and ligands over a period of several hours, each component being cleared from cells within 1 day. PCC-1 is relatively safe for cells at low micromolar concentrations but becomes inhibitory to cell proliferation and toxic above a concentration or incubation time threshold. However, cells surviving these conditions can return to homeostasis 3−5 days after exposure. Overall, these findings demonstrate that PCC-1 enters live cells by crossing biological membranes spontaneously. This should prove useful to deliver drugs that lack this capacity on their own, provided that the dosage and exposure time are controlled to avoid toxicity.

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Section: Discussionmentioning

confidence: 99%

Investigating the Cell Entry Mechanism, Disassembly, and Toxicity of the Nanocage PCC-1: Insights into Its Potential as a Drug Delivery Vehicle

Xiao,

Lin,

Drake

et al. 2023

J. Am. Chem. Soc.

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“…Several research approaches that combine the effects of metal oxides (MO) with targeting the acidic TME were developed in order to obtain enhanced antitumor efficacy. The interest on MO nanoparticles is due to their pro-apoptotic activity; inhibition of tumor cell growth and metastasis, and ROS production [ 231 , 232 ]. A characteristic example of an MO is cerium oxide nanoparticles (nanoceria).…”

Section: Nanomedicines For Targeting Tme: Application Of Natural and ...mentioning

confidence: 99%

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Avgoustakis,

Angelopoulou

2024

Pharmaceutics

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Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials’ properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.

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“…Chemotherapy resistance is often the main cause of chemotherapy failure, especially in MBC and TNBC, and it even accounts for approximately 90% of treatment failures (Nedeljkovic and Damjanovic, 2019). More and more studies have revealed that the development of resistance to MBC chemotherapy is complex and is based on several factors, including the interaction of TME, drug efflux, cancer stem cells, and bulk tumor cells, while changes in multiple signaling pathways control these interactions (Mao et al, 2013;Boelens et al, 2014;Luo et al, 2020;Gao et al, 2021;Subhan, 2022). At present, in-depth study of chemotherapy drugs has also found their adverse mechanism of action.…”

Section: Current Treatment Strategies and Challenges Of Bclmmentioning

confidence: 99%

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges

Miao,

Kang,

Zhang

2024

Front. Bioeng. Biotechnol.

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Lung metastasis of breast cancer is rapidly becoming a thorny problem in the treatment of patients with breast cancer and an obstacle to long-term survival. The main challenges of treatment are the absence of therapeutic targets and drug resistance, which promotes the development of nanotechnology in the diagnosis and treatment process. Taking advantage of the controllability and targeting of nanotechnology, drug-targeted delivery, controlled sustained release, multi-drug combination, improved drug efficacy, and reduced side effects can be realized in the process of the diagnosis and treatment of metastatic breast cancer (MBC). Several nanotechnology-based theranostic strategies have been investigated in breast cancer lung metastases (BCLM): targeted drug delivery, imaging analysis, immunotherapy, gene therapy, and multi-modality combined therapy, and some clinical applications are in the research phase. In this review, we present current nanotechnology-based diagnosis and treatment approaches for patients of incurable breast cancer with lung metastases, and we hope to be able to summarize more effective and promising nano-drug diagnosis and treatment systems that aim to improve the survival of patients with advanced MBC. We describe nanoplatform-based experimental studies and clinical trials targeting the tumor and the tumor microenvironment (TME) for BCLM to obtain more targeted treatment and in the future treatment steps for patients to provide a pioneering strategy.

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Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics

Abstract: Biomarker targeted therapy approaches for TNBC using metal oxide-based NPs are highly effective and promising.

Cited by 16 publications

References 201 publications

Investigating the Cell Entry Mechanism, Disassembly, and Toxicity of the Nanocage PCC-1: Insights into Its Potential as a Drug Delivery Vehicle

Investigating the Cell Entry Mechanism, Disassembly, and Toxicity of the Nanocage PCC-1: Insights into Its Potential as a Drug Delivery Vehicle

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges

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