Peptide directed phthalocyanine–gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers

Goddard, Zoë Rachael; Beekman, Andrew M.; Cominetti, Marco M. D.; O’Connell, Maria A.; Chambrier, Isabelle; Cook, Michael J.; Marín, María J.; Russell, David A.; Searcey, Mark

doi:10.1039/d0md00284d

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…Of these, AEYLR is of particular interest, as it shows a high binding affinity towards EGFR. The latter was conjugated to a 4 nm AuNP with a self-assembled mixed monolayer of the photosensitizer zinc phthalocyanine C11Pc and PEG [117]. The covalent binding of all components of this nanocarrier avoids any off-target phototoxicity due to desorption of the photosensitizer.…”

Section: Egfr-targeting Peptidesmentioning

confidence: 99%

“…Moreover, the EGFR-targeting peptide AEYLR was modified with a lysine residue at the C-terminus to allow the conjugation to the PEG (HS-PEG-COOH), and with a FITC-βAla at the N-terminus, allowing for imaging. This targeted nanosystem produces singlet oxygen upon irradiation at 633 nm, and a selective phototoxicity was observed for EGFR-overexpressing cells, displaying nanomolar potency and minimal dark toxicity [117].…”

Section: Egfr-targeting Peptidesmentioning

confidence: 99%

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EGFR-Targeted Photodynamic Therapy

et al. 2022

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The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer.

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Section: Egfr-targeting Peptidesmentioning

confidence: 99%

Section: Egfr-targeting Peptidesmentioning

confidence: 99%

EGFR-Targeted Photodynamic Therapy

et al. 2022

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“…No phototoxic response was recorded when the cells were incubated with non-targeted C11Pc-PEG-AuNps. It was concluded that the phototoxicity of peptide-C11Pc-PEG-AuNps was due to the dual effect of photocatalytic activity of C11Pc and the targeting effect [ 97 ]. Shiao et al developed gold nanoparticles modified with aptamer for co-drug delivery in photodynamic therapy.…”

Section: Inorganic and Organic Nanoparticulate For Active Or Passive ...mentioning

confidence: 99%

Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives

et al. 2022

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Numerous treatments are available for cancer, including chemotherapy, immunotherapy, radiation therapy, hormone therapy, biomarker testing, surgery, photodynamic therapy, etc. Photodynamic therapy (PDT) is an effective, non-invasive, novel, and clinically approved strategy to treat cancer. In PDT, three main agents are utilized, i.e., photosensitizer (PS) drug, oxygen, and light. At first, the photosensitizer is injected into blood circulation or applied topically, where it quickly becomes absorbed or accumulated at the tumor site passively or actively. Afterward, the tumor is irradiated with light which leads to the activation of the photosensitizing molecule. PS produces the reactive oxygen species (ROS), resulting in the death of the tumor cell. However, the effectiveness of PDT for tumor destruction is mainly dependent on the cellular uptake and water solubility of photosensitizer molecules. Therefore, the delivery of photosensitizer molecules to the tumor cell is essential in PDT against cancer. The non-specific distribution of photosensitizer results in unwanted side effects and unsuccessful therapeutic outcomes. Therefore, to improve PDT clinical outcomes, the current research is mostly focused on developing actively targeted photosensitizer molecules, which provide a high cellular uptake and high absorption capacity to the tumor site by overcoming the problem associated with conventional PDT. Therefore, this review aims to provide current knowledge on various types of actively and passively targeted organic and inorganic nanocarriers for different cancers.

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“…In another study, AuNPs were conjugated with a PS C11Pc and an EGFR peptide AEYLR to target EGFR markers expressed in lung cancer [ 86 ]. The study showed improved PDT effects, no dark toxicity, and the efficiency of a peptide as an excellent option for the delivery of AuNP-PS to tumor cells.…”

Section: Gold Nanoparticle Bioconjugates For Active Targeted Photodyn...mentioning

confidence: 99%

A Gold Nanoparticle Bioconjugate Delivery System for Active Targeted Photodynamic Therapy of Cancer and Cancer Stem Cells

Didamson

Chandran

Abrahamse

2022

Cancers

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Cancer stem cells (CSCs), also called tumor-initiating cells, are a subpopulation of cancer cells believed to be the leading cause of cancer initiation, growth, metastasis, and recurrence. Presently there are no effective treatments targeted at eliminating CSCs. Hence, an urgent need to develop measures to target CSCs to eliminate potential recurrence and metastasis associated with CSCs. Cancer stem cells have inherent and unique features that differ from other cancer cells, which they leverage to resist conventional therapies. Targeting such features with photodynamic therapy (PDT) could be a promising treatment for drug-resistant cancer stem cells. Photodynamic therapy is a light-mediated non-invasive treatment modality. However, PDT alone is unable to eliminate cancer stem cells effectively, hence the need for a targeted approach. Gold nanoparticle bioconjugates with PDT could be a potential approach for targeted photodynamic therapy of cancer and CSCs. This approach has the potential for enhanced drug delivery, selective and specific attachment to target tumor cells/CSCs, as well as the ability to efficiently generate ROS. This review examines the impact of a smart gold nanoparticle bioconjugate coupled with a photosensitizer (PS) in promoting targeted PDT of cancer and CSC.

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Peptide directed phthalocyanine–gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers

Abstract: Gold nanoparticles, covalently functionalised with the photosensitiser C11Pc and PEG, were actively targeted towards epidermal growth factor receptor overexpressing cancers using the peptide FITC-βAAEYLRK, with selective phototoxicty observed.

Cited by 12 publications

References 35 publications

EGFR-Targeted Photodynamic Therapy

EGFR-Targeted Photodynamic Therapy

Multifunctional Photoactive Nanomaterials for Photodynamic Therapy against Tumor: Recent Advancements and Perspectives

A Gold Nanoparticle Bioconjugate Delivery System for Active Targeted Photodynamic Therapy of Cancer and Cancer Stem Cells

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