Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells

Eloy, Josimar O.; Petrilli, Raquel; Brueggemeier, Robert W.; Marchetti, Juliana Maldonado; Lee, Robert J.

doi:10.2174/1871520616666160526103432

Cited by 30 publications

(14 citation statements)

References 52 publications

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“…FKBP1A, also named FKBP12, is a member of the FK-506-binding protein (FKBP) family, and its expression in cells is ubiquitous [43,44]. FKBP1A mediates the immunosuppressive and antitumor effects of rapamycin [45], widely used in the treatment of breast cancer [46,47]. One study on Eph receptors and invasive breast carcinoma suggested that the…”

Section: Plos Onementioning

confidence: 99%

Peripheral blood transcriptome identifies high-risk benign and malignant breast lesions

Hou

Jiang

Wang³

et al. 2020

PLoS ONE

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Background Peripheral blood transcriptome profiling is a potentially important tool for disease detection. We utilize this technique in a case-control study to identify candidate transcriptomic biomarkers able to differentiate women with breast lesions from normal controls. Methods Whole blood samples were collected from 50 women with high-risk breast lesions, 57 with breast cancers and 44 controls (151 samples). Blood gene expression profiling was carried out using microarray hybridization. We identified blood gene expression signatures using AdaBoost, and constructed a predictive model differentiating breast lesions from controls. Model performance was then characterized by AUC sensitivity, specificity and accuracy. Biomarker biological processes and functions were analyzed for clues to the pathogenesis of breast lesions. Results Ten gene biomarkers were identified (YWHAQ,

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Section: Plos Onementioning

confidence: 99%

Peripheral blood transcriptome identifies high-risk benign and malignant breast lesions

Hou

Jiang

Wang³

et al. 2020

PLoS ONE

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“…The treatment of breast cancer is complex and relies on several factors, including the type of tumor, tumor size, grade, proliferation rate and lymph node status. Existing treatment methods include surgery, chemotherapy, radiotherapy and hormonal treatments 3 . In recent years, the presence of breast cancer tumor markers has been investigated, and several markers were identi ed, including the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) 3,4 .…”

Section: Introductionmentioning

confidence: 99%

“…Existing treatment methods include surgery, chemotherapy, radiotherapy and hormonal treatments 3 . In recent years, the presence of breast cancer tumor markers has been investigated, and several markers were identi ed, including the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) 3,4 . Human epidermal growth factors belong to a family of transmembrane receptor tyrosine kinases (RTKs).…”

Section: Introductionmentioning

confidence: 99%

“…HER2 is involved in important stages of growth and cell differentiation and is normally expressed at low levels in the epithelial cells of various organs such as the lungs, bladder, pancreas, breast, and prostate 5,6 . HER2 overexpression can lead to malignant progression, which justi es the unfavorable prognosis of breast, ovarian, gastric, and prostate cancers 3 . HER2 overexpression is present in approximately 25% of all breast cancers and is usually associated with more aggressive disease and endocrine therapy resistance.…”

Section: Introductionmentioning

confidence: 99%

“…Studies showed that HER2 is uniformly distributed within the tumor and its expression induces signi cant apoptosis in breast cancer cells. These characteristics make it an appealing choice as a target in targeted therapy 3,5,6 .…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound-triggered Release of Calcein and Doxorubicin from HER2-targeted Liposomes in Breast Cancer Therapy

Amir

Ajith

AlSawaftah

et al. 2020

Preprint

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The functionalization of liposomes with antibodies is a potential strategy to increase the specificity of liposomes and reduce side-effects of chemotherapeutic agents. The active targeting of Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer cells can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized Calcein and Doxorubicin loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab. Both liposomes were characterized for size, phospholipid concentration and antibody conjugation. The effect of low-frequency ultrasound (LFUS)-induced drug release was tested using three power densities, 7.46, 9.85 and 17.31 mW/cm2; and the release data were modeled using six different kinetic models. LFUS results established the sonosensitivity of both carrier types, with immunoliposomes being more acoustically sensitive than control liposomes. Results also showed an increase in the release rate as the power density increased from 7.46 to 17.31 mW/cm2. Finally, the in vitro cell experiments showed enhanced uptake and cytotoxicity when breast cancer cell lines, SKBr3 and MDAMB-231, were treated with LFUS-triggered HER-liposomes.

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A Therapeutic Nanovaccine that Generates Anti‐Amyloid Antibodies and Amyloid‐specific Regulatory T Cells for Alzheimer's Disease

et al. 2022

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Alzheimer's disease (AD), the most common cause of dementia, is a complex condition characterized by multiple pathophysiological mechanisms including amyloid‐β (Aβ) plaque accumulation and neuroinflammation in the brain. The current immunotherapy approaches, such as anti‐Aβ monoclonal antibody (mAb) therapy, Aβ vaccines, and adoptive regulatory T (Treg) cell transfer, target a single pathophysiological mechanism, which may lead to unsatisfactory therapeutic efficacy. Furthermore, Aβ vaccines often induce T helper 1 (Th1) cell‐mediated inflammatory responses. Here, a nanovaccine composed of lipid nanoparticles loaded with Aβ peptides and rapamycin is developed, which targets multiple pathophysiological mechanisms, exhibits the combined effects of anti‐Aβ antibody therapy and adoptive Aβ‐specific Treg cell transfer, and can overcome the limitations of current immunotherapy approaches for AD. The Nanovaccine effectively delivers rapamycin and Aβ peptides to dendritic cells, produces both anti‐Aβ antibodies and Aβ‐specific Treg cells, removes Aβ plaques in the brain, alleviates neuroinflammation, prevents Th1 cell‐mediated excessive immune responses, and inhibits cognitive impairment in mice. The nanovaccine shows higher efficacy in cognitive recovery than an Aβ vaccine. Unlike anti‐Aβ mAb therapy and adoptive Treg cell transfer, both of which require complicated and costly manufacturing processes, the nanovaccine is easy‐to‐prepare and cost‐effective. The nanovaccines can represent a novel treatment option for AD.

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Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells

Cited by 30 publications

References 52 publications

Peripheral blood transcriptome identifies high-risk benign and malignant breast lesions

Peripheral blood transcriptome identifies high-risk benign and malignant breast lesions

Ultrasound-triggered Release of Calcein and Doxorubicin from HER2-targeted Liposomes in Breast Cancer Therapy

A Therapeutic Nanovaccine that Generates Anti‐Amyloid Antibodies and Amyloid‐specific Regulatory T Cells for Alzheimer's Disease

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