Study of efficiency of the modular nanotransporter for targeted delivery of photosensitizers to melanoma cell nuclei in vivo

Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets

“…injection. These results confirmed the ability of MNT to be selectively delivered to tumors bearing the receptor of interest in vivo [26, 28]. Immunohistochemical analyses of tumor and neighboring normal tissues isolated from Cloudman S91 melanoma bearing mice injected i.v.…”

“…Therefore, the problem of creating the optimal PS distribution in the cell becomes critical, especially taking into account that the most sensitive target for PSs is the cell nucleus [13, 22–24], where uptake of free PSs has not been detected [13, 25]. Thus, there exists a real possibility to significantly increase the effectiveness of PSs by achieving their delivery to the nucleus of target cells, reducing doses required to reach a therapeutic threshold, and thus diminishing side effects [8, 26–28]. …”

“…Currently, several kinds of MNTs [8, 16, 29], including the most extensively studied versions with ligands for melanocortin receptor type 1 (MC1R) [12, 24, 26, 28] and epidermal growth factor receptor (EGFR) [22, 23, 25–27, 37, 38] have been created. However, numerous growth factor receptors are known whose expression is highly increased during tumorigenesis.…”

Preparation, cytotoxicity, and in vivo antitumor efficacy of ¹¹¹In-labeled modular nanotransporters

“…9,36 Potentially germane to the current studies with 111 In-NOTA-MNT-EGF, Chen et al 37 reported significant growth inhibition of In-MNT-EGF construct in the present article; however, we do note that in a previous study using residualizing 125 I labeling, the in vitro cytotoxicity of [ For in vivo proof-of-principle experiments, we selected MNT-MSH, targeted to melanoma cells, which overexpress MC1R. 38 This MNT has been regarded recently as a promising approach for the treatment of malignant melanoma, [39][40][41] including uveal melanoma. 42 Although skin melanomas are usually managed by surgical excision, ocular melanomas are routinely treated with brachytherapy.…”

Malignant melanoma and melanocortin 1 receptor

“…Moreover, non-isotope methods of melanoma treatment based on MC1R selectivity, such as photodynamic therapy and suicide gene therapy, have therapeutic potential as well. For example, the photosensitizer bacteriochlorin p conjugated to modular transporter DTox-HMP-NLS-MSH, delivered into the cell nuclei of experimental mouse melanomas, inhibits tumor growth by 80–98% and increases survival 1.6–2.5-fold after a course of photodynamic therapy [86, 87]. Incorporation of a peptide highly specific for MC1R into a synthetic gene-delivering construct resulted in significantly improved melanoma suicide therapy using polyplexes carrying the Herpes simplex virus thymidine kinase gene [128].…”