Bio-Applications of Multifunctional Melanin Nanoparticles: From Nanomedicine to Nanocosmetics

Abstract

Bioinspired nanomaterials are ideal components for nanomedicine, by virtue of their expected biocompatibility or even complete lack of toxicity. Natural and artificial melanin-based nanoparticles (MNP), including polydopamine nanoparticles (PDA NP), excel for their extraordinary combination of additional optical, electronic, chemical, photophysical, and photochemical properties. Thanks to these features, melanin plays an important multifunctional role in the design of new platforms for nanomedicine where this material works not only as a mechanical support or scaffold, but as an active component for imaging, even multimodal, and simple or synergistic therapy. The number of examples of bio-applications of MNP increased dramatically in the last decade. Here, we review the most recent ones, focusing on the multiplicity of functions that melanin performs in theranostics platforms with increasing complexity. For the sake of clarity, we start analyzing briefly the main properties of melanin and its derivative as well as main natural sources and synthetic methods, moving to imaging application from mono-modal (fluorescence, photoacoustic, and magnetic resonance) to multi-modal, and then to mono-therapy (drug delivery, anti-oxidant, photothermal, and photodynamic), and finally to theranostics and synergistic therapies, including gene- and immuno- in combination to photothermal and photodynamic. Nanomedicine aims not only at the treatment of diseases, but also to their prevention, and melanin in nature performs a protective action, in the form of nanopigment, against UV-Vis radiations and oxidants. With these functions being at the border between nanomedicine and cosmetics nanotechnology, recently examples of applications of artificial MNP in cosmetics are increasing, paving the road to the birth of the new science of nanocosmetics. In the last part of this review, we summarize and discuss these important recent results that establish evidence of the interconnection between nanomedicine and cosmetics nanotechnology.

Keywords: biocompatible; bioimaging; drug delivery; melanin; nanomedicine; nanotoxicity; photodynamic therapy; photothermal therapy; polydopamine; theranostics.

Figure 1

Scheme summarizing the interconnections between melanin, MNP and their applications. Melanin in nature is responsible for photoprotection and coloration. Its properties inspired the development of MNP for imaging and therapy and finally for theranostics in nanomedicine. Recently MNP have been considered as a supplement to natural melanin for photoprotection and coloration contributing to the development of nanocosmetics.

Figure 2

Reactions involved in the formation of natural pheomelanin, eumelanin and neuromelanin starting from tyrosine.

Figure 3

(a) UV-Vis-NIR absorption spectrum of DOPA melanin in aqueous solution (black line). Hypothetical distinct chromophores, some of which can be selectively excited at selected wavelength (black arrow), are shown as colored Gaussian functions. (b) Synthesis of DOPA melanin: L-DOPA oxidation produces DHI and DHICA intermediates that polymerize to give the typical structural motifs proposed for eumelanin shown in (c) and (d). Adapted from [69], with permission from Royal Society of Chemistry, 2020.

Figure 4

(A) Synthesis of polydopamine-based NP. (B) Radical-enriched MNP result from the copolymerization of dopamine with radical monomers generates. (C) TEM images of the NP. (D) Confocal microscopy of NHEK live-cells after incubating radical NPs. Adapted from [35], with permission from American Chemical Society, 2020.

Figure 5

(a) Au@mPDA loading with protein. Intracellular delivery and release of (b) GFP and (c) RNaseproteins activated by NIR irradiation. Reproduced from [108], with permission from Elsevier, 2020.

Figure 6

Scheme of the formation of OMVMel (OMV is outer membrane vesicle): OMVMel is purified after vesiculation from the parental bacteria. Reproduced from [116], with permission from Springer Nature, 2019.

Figure 7

Scheme of the synthesis of MNP loaded with metal ions proposed as MRI contrast agents. Reproduced from [36], with permission from Royal Society of Chemistry, 2020.

Figure 8

Scheme of the formation of PPy–PDA Hybrid Nanoshells. The energy transfer process between the components is also schematized. Reproduced from [135], with permission from American Chemical Society, 2018.

Figure 9

Scheme of the synthesis of MMPP for PET/MR bimodal imaging-guided AKI therapy. The activity of the NP as a naturally antioxidative platform is also schematized. Adapted from [140], with permission from John Wiley and Sons, 2019.

Figure 10

Scheme showing the neuroprotective action of Metformin nanoformulation (Met loaded PDANPs). Resulting NP inhibit rotenone-induced neurotoxicity by promoting EZH2 mediated α-Synuclein ubiquitination and degradation to prevent PD pathogenesis. Reproduced from [147], with permission from Elsevier, 2020.

Figure 11

Scheme of preparation of doxorubicin/T-pDA-Fe₃O₄ NP conjugates. Sulfonamide link is exploited as pH-responsive group to activate the release of drug. Reproduced from [153], with permission from American Chemical Society, 2020.

Figure 12

Beclin 1-induced autophagy was exploited for photothermal killing of cancer cells. Internalization of PPBR by cancer cells, via RGD-αvβ3 recognition, was exploited while Beclin 1, bound to the NP surface, contributed to up-regulate autophagy to sensitize cancer cells to PTT. Reproduced from [171], with permission from Elsevier, 2019.

Figure 13

Scheme showing the role of CINPs in inhibiting tumor growth by producing macrophage repolarization and activating synergistic photothermal therapy. Reproduced from [181], with permission from American Chemical Society, 2019.

Figure 14

Structure of the OBX loaded MMNs (OBX-MMNs) for PA/MR multimodality imaging guided mild hyperthermia-enhanced chemotherapy. OBX is exploited as an inhibitor of the Wnt/β-catenin signaling pathway. Reproduced from [194], with permission from Elsevier, 2020.

Figure 15

Scheme of the preparation of PDA-coated nucleic acid nanogel and its application in siRNA-mediated low-temperature PTT in vivo. (A) Synthesis of PDA-coated nucleic acid nanogel with PEGylated surface (PEG-PDA-Nanogel). (B) Processes involved in the siRNA-mediated low-temperature photothermal therapy induced by PEG-PDA-Nanogel. Reproduced from [201], with permission from Elsevier, 2020.

Figure 16

Schematic illustration of the preparation of BV/PTX@Au@PDA/DOX NP (top) and of the hierarchical drug release process (bottom) that combine pH-activated and NIR-triggered localized/systematic cascade cancer therapy in tumor-bearing mice. Reproduced from [209], with permission from Ivyspring International Publisher, 2019.

Figure 17

Scheme of the preparation and application of AmmRBCs for tumor therapy. (A) Preparation of AmmRBC. (B) Accumulation of AmmRBCs in tumor site enhances singlet oxygen generation for more efficient PDT. (C) PDA in AmmRBC mimics CAT and SOD in RBC to protect Hb from oxidant damage during the circulation. Reproduced from [220], with permission from John Wiley and Sons, 2018.

Figure 18

Schematic illustration showing synthesis, delivery, and the process of T-ZnPc release from PATP NP for its PTT/PDT treatment to tumor. Reproduced from [120], with permission from John Wiley and Sons, 2019.

Figure 19

Schematic illustration of the preparation of allomelanin NP. Confocal microscopy images of NHEK cells incubated the NP are also shown. Reproduced from [58], with permission from American Chemical Society, 2019.

Figure 20

Schematic illustration of the synthesis of PDA NP and optical and SEM images of hair before and after treatment with the NP. Reproduced from [246], with permission from American Chemical Society, 2020.