EGF Receptor-Targeted Nanocarriers for Enhanced Cancer Treatment

Master, Аlyssa M.; Gupta, Anirban Sen

doi:10.2217/nnm.12.160

Cited by 124 publications

(86 citation statements)

References 81 publications

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“…From this approach, liposomes can be surface decorated with receptor recognition ligands including antibodies, aptamers, peptides, and integrins to facilitate targeting of specific biomarkers that are identified in disease states. For example, EGFR [38], Folate Receptor [39, 40], and HER2 [41] directed nanotherapies have significantly improved global cancer treatment via cell specific endocytosis of therapeutic cargo. In regards to GBM therapy, a wide array of active recognition ligands have been utilized to date including the peptide sequences IL13 [42, 43], CGKRK [44], Pep1 [45], activatable low molecular weight protamine [46], and chlorotoxin [47], antibodies such as EGFRvIII [48], low density lipoprotein receptor related proteins [49, 50], and the GMT8 aptamer [51].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

2016

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Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study the uptake pathway in key cells in the brain including primary astrocytes, microglia, and human GBM cells. We observed that the HALNPs specifically target GBM cells over other brain cells due to higher expression of CD44 in tumor cells. Furthermore, CD44 driven HALNP uptake into GBM cells resulted in lysosomal evasion and increased efficacy of Doxorubicin, a model anti-neoplastic agent, while the astrocytes and microglia cells exhibited extensive HALNP-lysosome co-localization and decreased antineoplastic potency. In summary, novel CD44 targeted lipid based nanocarriers appear to be proficient in mediating site-specific delivery of drugs via CD44 receptors in GBM cells, with an improved therapeutic margin and safety.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

2016

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“…Another study evaluated the application of EGF for skin patches, showing the resistance of this peptide to temperature (T m ~ 79°C) [6]. However, the potential physiological activation and stimulation of cancer growth has hindered the use of EGF as targeting peptide in drug delivery systems, which is dependent on the release of the anticancer drug [7]. When conjugated to metallic nanoparticles, EGF promotes a rapid internalization into cancer cells [8], and cancer destruction can be achieved by injecting the light-absorbing nanoparticles locally and applying the laser-mediated hyperthermia directly into the tumour.…”

Section: Introductionmentioning

confidence: 99%

EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy

et al. 2016

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The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100–200 nm) showed a plasmon absorption band located within the near-infrared range (650–900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0–25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.

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“…The epidermal growth factor receptor (EGFR) is a 170-kD glycoprotein which belongs to the ErbB family of tyrosine kinase receptors. The EGFR plays a crucial role in cancer progression and metastasis since it activates signaling pathways responsible for promoting cell proliferation, angiogenesis, and inhibiting apoptosis [38]. Overexpression of EGFR has been observed in various types of cancer, including breast, lung, colon, ovarian, pancreatic, and kidney cancers [2].…”

Section: Active Targeting Of Tumor Cellsmentioning

confidence: 99%

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

Porfire¹,

Achim²,

Tefas³

et al. 2017

Liposomes

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The liposomes present great potential for applications in targeted delivery of chemotherapeutics in the treatment of cancer. The use of liposomal drug carriers as vehicles for targeting of chemotherapeutic agents to tumor tissues is based on their advantages over other dosage forms, represented by their low systemic toxicity, their bioavailability, and their possibility to enhance the solubility of different chemotherapeutic agents, due to the ability to encapsulate both hydrophilic and lipophilic drugs. They enhance the therapeutic index of anticancer drugs by increasing the drug concentration in tumor cells through tumor targeting. The available approaches used for tumor targeting using liposomes are passive targeting, active targeting, and triggered drug release. The most advanced targeting strategies proposed for cancer treatment are the development of multifunctional liposomes, having combined targeting mechanism. In this chapter, the tumor-targeting mechanisms are described in detail as well as the possibilities to design the targeted liposomal nanocarrier in order to reach the desired target in the body and minimizing the off-target effects. Moreover, the current status of preclinical and clinical evaluation is highlighted.

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EGF Receptor-Targeted Nanocarriers for Enhanced Cancer Treatment

Cited by 124 publications

References 81 publications

Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells

EGF Functionalized Polymer-Coated Gold Nanoparticles Promote EGF Photostability and EGFR Internalization for Photothermal Therapy

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

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