Dual targeting of folate receptor-expressing glioma tumor-associated macrophages and epithelial cells in the brain using a carbon nanosphere–cationic folate nanoconjugate

Elechalawar, Chandra Kumar; Bhattacharya, Debapriya; Ahmed, Mohammed Tanveer; Gora, Halley; Sridharan, Kathyayani; Chaturbedy, Piyush; Sinha, Sarmistha; Jaggarapu, Madhan Mohan Chandra Sekhar; Narayan, Kumar Pranav; Chakravarty, Sumana; Eswaramoorthy, M.; Kundu, Tapas K.; Banerjee, Rajkumar

doi:10.1039/c9na00056a

Cited by 35 publications

(24 citation statements)

References 50 publications

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“…Once Folate-FITC binds to the folate receptor, endocytosis occurs slowly with the fluorescent conjugation persisting within the cell after 2 h [ 19 ]. Indeed, GBM tumours display a high expression of FR-α, rendering this receptor a potential target for brain tumour-specific fluorescence imaging [ 56 , 73 ]. Effective targeting of GBM via FR requires the consideration of other FR expressing components of the tumour microenvironment (TME), such as tumour-associated macrophages (TAMs) [ 56 ].…”

Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

“…Indeed, GBM tumours display a high expression of FR-α, rendering this receptor a potential target for brain tumour-specific fluorescence imaging [ 56 , 73 ]. Effective targeting of GBM via FR requires the consideration of other FR expressing components of the tumour microenvironment (TME), such as tumour-associated macrophages (TAMs) [ 56 ]. The TAMs constitute up to 50% of tumour bulk in GBM and have been shown to play an important role in tumour maintenance and progression [ 74 ].…”

Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

“…However, FR is only moderately expressed within TAMs, presenting a challenge to target them specifically. It has been suggested to overcome this challenge through the use of recently developed Carbon nanosphere technology [ 56 ]. Carbon nanospheres (CSPs) are distinguished by their ability to cross the BBB and may improve the targeting of FRs specifically on GBM cells [ 56 ].…”

Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

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Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents

et al. 2022

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Glioblastoma (GBM) is the most aggressive adult brain tumour with a dismal 2-year survival rate of 26–33%. Maximal safe resection plays a crucial role in improving patient progression-free survival (PFS). Neurosurgeons have the significant challenge of delineating normal tissue from brain tumour to achieve the optimal extent of resection (EOR), with 5-Aminolevulinic Acid (5-ALA) the only clinically approved intra-operative fluorophore for GBM. This review aims to highlight the requirement for improved intra-operative imaging techniques, focusing on fluorescence-guided imaging (FGS) and the use of novel dyes with the potential to overcome the limitations of current FGS. The review was performed based on articles found in PubMed an.d Google Scholar, as well as articles identified in searched bibliographies between 2001 and 2022. Key words for searches included ‘Glioblastoma’ + ‘Fluorophore’+ ‘Novel’ + ‘Fluorescence Guided Surgery’. Current literature has favoured the approach of using targeted fluorophores to achieve specific accumulation in the tumour microenvironment, with biological conjugates leading the way. These conjugates target specific parts overexpressed in the tumour. The positive results in breast, ovarian and colorectal tissue are promising and may, therefore, be applied to intracranial neoplasms. Therefore, this design has the potential to produce favourable results in GBM by reducing the residual tumour, which translates to decreased tumour recurrence, morbidity and ultimately, mortality in GBM patients. Several preclinical studies have shown positive results with targeted dyes in distinguishing GBM cells from normal brain parenchyma, and targeted dyes in the Near-Infrared (NIR) emission range offer promising results, which may be valuable future alternatives.

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Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

Section: Novel Dyes In Pre-clinical Developmentmentioning

confidence: 99%

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Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents

et al. 2022

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“…The study findings were very promising. FR has been successfully used for dual targeting of tumor cells and tumor associated macrophages in the tumor microenvironment including active targeting in glioma orthotopic model in situ (Elechalawar et al, 2019). The same ligand has been used for liposomal delivery of a ER-targeting drug to treat melanoma tumor through caspase-8 mediated extrinsic pathway of apoptosis (Elechalawar et al, 2017).…”

Section: Targeted Cancer Therapeutics: a Brief Account Of Cancer Trea...mentioning

confidence: 99%

Targeting steroid hormone receptors for anti‐cancer therapy—A review on small molecules and nanotherapeutic approaches

Mahadik

Bhattacharya

Padmanabhan

et al. 2021

WIREs Nanomed Nanobiotechnol

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The steroid hormone receptors (SHRs) among nuclear hormone receptors (NHRs) are steroid ligand-dependent transcription factors that play important roles in the regulation of transcription of genes promoted via hormone responsive elements in our genome. Aberrant expression patterns and contextspecific regulation of these receptors in cancer, have been routinely reported by multiple research groups. These gave an window of opportunity to target those receptors in the context of developing novel, targeted anticancer therapeutics. Besides the development of a plethora of SHR-targeting synthetic ligands and the availability of their natural, hormonal ligands, development of many SHR-targeted, anticancer nano-delivery systems and theranostics, especially based on small molecules, have been reported. It is intriguing to realize that these cytoplasmic receptors have become a hot target for cancer selective delivery. This is in spite of the fact that these receptors do not fall in the category of conventional, targetable cell surface bound or transmembrane receptors that enjoy over-expression status. Glucocorticoid receptor (GR) is one such exciting SHR that in spite of it being expressed ubiquitously in all cells, we discovered it to behave differently in cancer cells, thus making it a truly druggable target for treating cancer. This review selectively accumulates the knowledge generated in the field of SHR-targeting as a major focus for cancer treatment with various anticancer small molecules and nanotherapeutics on progesterone receptor, mineralocorticoid receptor, and androgen receptor while selectively emphasizing on GR and estrogen receptor. This review also briefly highlights lipid-modification strategy to convert ligands into SHRtargeted cancer nanotherapeutics.

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“…Folate receptors are a particular interest for targeted delivery in GBM since one of the folate receptors, FRα, is highly expressed in gliomas but is very low on normal cells [52]. Kefayet et al [53] prepared folic acid-and BSA-coupled gold nanoclusters (FA-AuNCs) to explore their radiosensitizing capacity on C6 glioma tumors.…”

Section: Application Of Nanodrugs As Radiosensitizers For Gbm Therapymentioning

confidence: 99%

SapC–DOPS as a Novel Therapeutic and Diagnostic Agent for Glioblastoma Therapy and Detection: Alternative to Old Drugs and Agents

et al. 2021

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Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%. Standard-of-care treatment includes maximal surgical removal of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. TMZ is the “gold-standard” chemotherapy for patients suffering from GBM. However, the median survival is only about 12 to 18 months with this protocol. Consequently, there is a critical need to develop new therapeutic options for treatment of GBM. Nanomaterials have unique properties as multifunctional platforms for brain tumor therapy and diagnosis. As one of the nanomaterials, lipid-based nanocarriers are capable of delivering chemotherapeutics and imaging agents to tumor sites by enhancing the permeability of the compound through the blood–brain barrier, which makes them ideal for GBM therapy and imaging. Nanocarriers also can be used for delivery of radiosensitizers to the tumor to enhance the efficacy of the radiation therapy. Previously, high-atomic-number element-containing particles such as gold nanoparticles and liposomes have been used as radiosensitizers. SapC–DOPS, a protein-based liposomal drug comprising the lipid, dioleoylphosphatidylserine (DOPS), and the protein, saposin C (SapC), has been shown to be effective for treatment of a variety of cancers in small animals, including GBM. SapC–DOPS also has the unique ability to be used as a carrier for delivery of radiotheranostic agents for nuclear imaging and radiotherapeutic purposes. These unique properties make tumor-targeting proteo-liposome nanocarriers novel therapeutic and diagnostic alternatives to traditional chemotherapeutics and imaging agents. This article reviews various treatment modalities including nanolipid-based delivery and therapeutic systems used in preclinical and clinical trial settings for GBM treatment and detection.

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Dual targeting of folate receptor-expressing glioma tumor-associated macrophages and epithelial cells in the brain using a carbon nanosphere–cationic folate nanoconjugate

Abstract: A carbon nanosphere-based dual strategy to target tumor-associated macrophages and tumor cells in glioma lesions within the brain.

Cited by 35 publications

References 50 publications

Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents

Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents

Targeting steroid hormone receptors for anti‐cancer therapy—A review on small molecules and nanotherapeutic approaches

SapC–DOPS as a Novel Therapeutic and Diagnostic Agent for Glioblastoma Therapy and Detection: Alternative to Old Drugs and Agents

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