Specific Targeting of Melanotic Cells with Peptide Ligated Photosensitizers for Photodynamic Therapy

Abstract

A strategy combining covalent conjugation of photosensitizers to a peptide ligand directed to the melanocortin 1 (MC1) receptor with the application of sequential LED light dosage at near-IR wavelengths was developed to achieve specific cytotoxicity to melanocytes and melanoma (MEL) with minimal collateral damage to surrounding cells such as keratinocytes (KER). The specific killing of melanotic cells by targeted photodynamic therapy (PDT) described in this study holds promise as a potentially effective adjuvant therapeutic method to control benign skin hyperpigmentation or superficial melanotic malignancy such as Lentigo Maligna Melanoma (LMM).

Near-Infrared Light Activates Molecular Nanomachines to Drill into and Kill Cells

“…cancer cell lines where light-activation is amenable. 24,25 This could be a photodynamic therapy using a non-invasive approach that can also be coupled with extremely high 3D optical precision. Since the entry of the PI is on a relatively short time scale compared to the time of cell division, the cell has insufficient time to adopt programmed cell death (apoptosis).…”

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

“…The results showed that DOC/peptide NPs can inhibit tumor growth compared to that in the group without peptide, demonstrating the effectiveness of this bifunctional peptide-based vehicle. [87] The resulting peptide was conjugated to the photosensitizer δ-aminolevulinic acid (ALA) and targeted melanoma cells. [82] Hong et al synthesized a cRGD peptidepyropheophorbide-a (Pyro) conjugate for PDT.…”

“…For PDT, an octapeptide derivative of a chelator (DOTA)-modified α-melanocyte-stimulating hormone (α-MSH) was bound specifically to the melanocortin 1 (MC1) receptor. [87] The resulting peptide was conjugated to the photosensitizer δ-aminolevulinic acid (ALA) and targeted melanoma cells. Van Lier et al synthesized several conjugates using bombesin (BBN) (Tyr-Gln-ArgLeu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2) and phthalocyanine to target the gastrin-releasing peptide receptors.…”

“…This conjugate was cleaved by PSA to release TGX‐221 for prostate cancer treatment. For PDT, an octapeptide derivative of a chelator (DOTA)‐modified α‐melanocyte‐stimulating hormone (α‐MSH) was bound specifically to the melanocortin 1 (MC1) receptor . The resulting peptide was conjugated to the photosensitizer δ‐aminolevulinic acid (ALA) and targeted melanoma cells.…”

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

“…Alongside high production costs, heterogeneity of samples can result in poor reproducibility. Recently, the targeting ability of peptides has increased in popularity [10][11][12][13][14][15] as these chemically synthesised molecules can overcome many of the disadvantages that proteins present, while still maintaining selectivity towards the desired target.…”