In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

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Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

Current Alzheimer Research ◽

10.2174/1567205017666201130085853 ◽

2020 ◽

Vol 17 ◽

Author(s):

Reem Habib Mohamad Ali Ahmad ◽

Marc Fakhoury ◽

Nada Lawand

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

In Vivo Studies ◽

Key Factors ◽

Potential Benefits ◽

Preclinical And Clinical Studies ◽

The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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Multiple-Armed Tetrahedral DNA Nanostructures for Tumor-Targeting, Dual-Modality in Vivo Imaging

ACS Applied Materials & Interfaces ◽

10.1021/acsami.5b10792 ◽

2016 ◽

Vol 8 (7) ◽

pp. 4378-4384 ◽

Cited By ~ 74

Author(s):

Dawei Jiang ◽

Yanhong Sun ◽

Jiang Li ◽

Qian Li ◽

Min Lv ◽

...

Keyword(s):

In Vivo Imaging ◽

Tumor Targeting ◽

Dna Nanostructures ◽

Dual Modality

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The methyltransferase SETD2 couples transcription and splicing by engaging mRNA processing factors through its SHI domain

Nature Communications ◽

10.1038/s41467-021-21663-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Saikat Bhattacharya ◽

Michaella J. Levy ◽

Ning Zhang ◽

Hua Li ◽

Laurence Florens ◽

...

Keyword(s):

Rna Splicing ◽

Rna Binding ◽

Mrna Processing ◽

Key Factors ◽

Pol Ii ◽

Mrna Transcripts ◽

Hnrnp Protein ◽

Processing Factors

AbstractHeterogeneous ribonucleoproteins (hnRNPs) are RNA binding molecules that are involved in key processes such as RNA splicing and transcription. One such hnRNP protein, hnRNP L, regulates alternative splicing (AS) by binding to pre-mRNA transcripts. However, it is unclear what factors contribute to hnRNP L-regulated AS events. Using proteomic approaches, we identified several key factors that co-purify with hnRNP L. We demonstrate that one such factor, the histone methyltransferase SETD2, specifically interacts with hnRNP L in vitro and in vivo. This interaction occurs through a previously uncharacterized domain in SETD2, the SETD2-hnRNP Interaction (SHI) domain, the deletion of which, leads to a reduced H3K36me3 deposition. Functionally, SETD2 regulates a subset of hnRNP L-targeted AS events. Our findings demonstrate that SETD2, by interacting with Pol II as well as hnRNP L, can mediate the crosstalk between the transcription and the splicing machinery.

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Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00501-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Tong Shen ◽

Jing-Lin Liu ◽

Chu-Yi Wang ◽

Youlutuziayi Rixiati ◽

Shi Li ◽

...

Keyword(s):

B Cells ◽

Lung Metastasis ◽

Lung Metastases ◽

Pdz Domain ◽

Clinical Samples ◽

Key Factors ◽

Combined Use ◽

Iga Production

AbstractThe mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases. Erbin deletion in B cells suppressed lung metastasis of CRC in vivo. And, deletion of Erbin in B cells enhanced the killing effects of CD8+ T cells on tumor cells. Mechanistically, Erbin knockout attenuated TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression. Our study uncovered a key role of Erbin in regulating PD1+ IgA+ B cells in lung metastasis of CRC. Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice, suggesting the potential option for treatment of lung metastasis of CRC.

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Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02039-w ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Lisa Agnello ◽

Silvia Tortorella ◽

Annachiara d’Argenio ◽

Clarissa Carbone ◽

Simona Camorani ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Tumor Targeting ◽

Triple Negative ◽

Ex Vivo ◽

Treatment Options ◽

Negative Control ◽

Therapeutic Effects ◽

Metastatic Setting

Abstract Background Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. Methods Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. Results We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. Conclusions Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

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