Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

Figures & data

Figure 1. Energy transfer in photodynamic therapy. Following a light beam, the photosensitizer reaches an excited singlet state and moves to a triplet excited state. The excited triplet photosensitizer reacts directly with oxygen through energy transfer generating activated oxygen.

Figure 2. Mechanism of cytocidal effect of photodynamic therapy. Irradiation with light beam induces the formation of activated oxygen through energy transfer. Activated oxygen is highly reactive and cytotoxic. It reacts with biomolecules (i.e. lipids, proteins, and nucleic acids of cellular or lysosomal origin) inducing cell death through activation of the apoptotic pathway.

Table 1. A list of photodynamic molecules used in PDT.

Compound	Structure	References
Acai oil		^107
Acridine orange (AO)		^29
5-Aminolevulinic acid (ALA)		^109–111
Chlorins		^112–115
C-Phycocyanin		^116
Cyclodextrin		^117^,^118
Coumarin derivative		^119^,^120
Curcumin		^121^,^122
DPAO2		^123
DPP-ZnP/DPP-ZnP-DPP		^124
Erythrosine		^125
Folate–albumin–photosensitizer conjugate
Hypericin		^126–130
Methylene blue (MB)		^43^,^131^,^132
PdTPPo/TPPo		^133
Phthalocyanines		^62^,^65^,^66^,^68
PPaN-20		^134
Porphyrin		^135–141
PyP/yPyyPy/porphycenes		^142
Quinone		^143

Monge-Fuentes V, Muehlmann LA, Longo JP, et al. Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: a potential treatment for melanoma. J Photochem Photobiol B 2017;166:301–10.

 PubMed Web of Science ®Google Scholar

Kusuzaki K, Hosogi S, Ashihara E, et al. Translational research of photodynamic therapy with acridine orange which targets cancer acidity. Curr Pharm Des 2012;18:1414–20.

 PubMed Web of Science ®Google Scholar

Conte C, Scala A, Siracusano G, et al. Nanoassembly of an amphiphilic cyclodextrin and Zn(II)-phthalocyanine with the potential for photodynamic therapy of cancer. RSC Advances 2014;4:43903–11.

 Web of Science ®Google Scholar

Lourenco LMO, Pereira PM, Maciel E, et al. Amphiphilic phthalocyanine-cyclodextrin conjugates for cancer photodynamic therapy. Chem Commun 2014;50:8363–6.

 PubMed Web of Science ®Google Scholar

Medina FG, Marrero JG, Macías-Alonso M, et al. Coumarin heterocyclic derivatives: chemical synthesis and biological activity. Nat Prod Rep 2015;32:1472–507.

 PubMed Web of Science ®Google Scholar

Wu H, Zeng F, Zhang H, et al. A nanosystem capable of releasing a photosensitizer bioprecursor under two-photon irradiation for photodynamic therapy. Adv Sci (Weinh) 2015;3:1500254.

 PubMedGoogle Scholar

Lee WH, Loo CY, Bebawy M, et al. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol 2013;11:338–78.

 PubMed Web of Science ®Google Scholar

Haukvik T, Bruzell E, Kristensen S, Tønnesen HH. Photokilling of bacteria by curcumin in selected polyethylene glycol 400 (peg 400) preparations. Studies on curcumin and curcuminoids, xli. Pharmazie 2010;65:600–6.

 PubMed Web of Science ®Google Scholar

LoTempio MM, Veena MS, Steele HL, et al. Curcumin suppresses growth of head and neck squamous cell carcinoma. Clin Cancer Res 2005;11:6994–7002.

 PubMed Web of Science ®Google Scholar

Duco W, Grosso V, Zaccari D, Soltermann AT. Generation of ROS mediated by mechanical waves (ultrasound) and its possible applications. Methods 2016;109:141–8.

 PubMed Web of Science ®Google Scholar

Schmitt J, Heitz V, Sour A, et al. Diketopyrrolopyrrole-porphyrin conjugates with high two-photon absorption and singlet oxygen generation for two-photon photodynamic therapy. Angew Chem Int Ed Engl 2015;54:169–73.

 PubMed Web of Science ®Google Scholar

Letuta SN, Pashkevich SN, Ishemgulov AT, et al. Delayed luminescence of erythrosine in biological tissue and photodynamic therapy dosimetry. J Photochem Photobiol B 2016;163:232–6.

 PubMed Web of Science ®Google Scholar

Tardivo JP, del Giglio A, de Oliveira CS, et al. Methylene blue in photodynamic therapy: from basic mechanisms to clinical applications. Photodiagn Photodyn Ther 2005;2:175–91.

 PubMed Web of Science ®Google Scholar

De Freitas LM, Soares CP, Fontana CR. Synergistic effect of photodynamic therapy and cisplatin: a novel approach for cervical cancer. J Photochem Photobiol B Biol 2014;140:365–73.

 PubMed Web of Science ®Google Scholar

Samy NA, Salah MM, Ali MF, Sadek AM. Effect of methylene blue-mediated photodynamic therapy for treatment of basal cell carcinoma. Lasers Med Sci 2014;30:109–15.

 PubMed Web of Science ®Google Scholar

Arnbjerg J, Jiménez-Banzo A, Paterson MJ, et al. Two-photon absorption in tetraphenylporphycenes: are porphycenes better candidates than porphyrins for providing optimal optical properties for two-photon photodynamic therapy? J Am Chem Soc 2007;129:5188–99.

 PubMed Web of Science ®Google Scholar

Şahin B, Topal SZ, Atilla D. Synthesis, photophysical and photochemical properties of a set of silicon phthalocyanines bearing anti-inflammatory groups. J Fluoresc 2017;27:407–16.

 PubMed Web of Science ®Google Scholar

Ranyuk E, Cauchon N, Klarskov K, et al. Phthalocyanine-peptide conjugates: receptor-targeting bifunctional agents for imaging and photodynamic therapy. J Med Chem 2013;56:1520–34.

 PubMed Web of Science ®Google Scholar

Swavey S, Tran M, Porphyrin and phthalocyanine photosensitizers as pdt agents: a new modality for the treatment of melanoma. In: David LM, ed. Recent advances in the biology, therapy and management of melanoma. INTECH Open Access Publisher: Rijeka, Croatia; 2013. p. 253–82.

 Google Scholar

Zasedatelev AV, Dubinina TV, Krichevsky DM, et al. Plasmon-induced light absorption of phthalocyanine layer in hybrid nanoparticles: enhancement factor and effective spectra. J Phys Chem C 2016;120:1816–23.

 Web of Science ®Google Scholar

Jeong K, Park S, Lee YD, et al. Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer. Colloids Surf B Biointerfaces 2016;144:303–10.

 PubMed Web of Science ®Google Scholar

Drobizhev M, Stepanenko Y, Dzenis Y, et al. Extremely strong near-IR two-photon absorption in conjugated porphyrin dimers: quantitative description with three-essential-states model. J Phys Chem B 2005;109:7223–36.

 PubMed Web of Science ®Google Scholar

KR, PR Fernandez A, Laila SP, B, et al. Synthesis, spectral characterization, crystal structure, cytotoxicity and apoptosis – inducing activity of two derivatives of 2-hydroxy-1,4-naphthaquinone. Photodiagnosis Photodyn Ther 2017;17:250–9.

 PubMed Web of Science ®Google Scholar