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1.
J Mater Chem B ; 9(12): 2845-2853, 2021 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-33704321

RESUMEN

Photothermal therapy (PTT) is a promising strategy for cancer treatment. However, the development of highly efficient photothermal agents with excellent biosafety, particularly with low liver retention, is very meaningful for clinical applications, but it is also challenging. We herein prepared a pH-sensitive nanoagent (NanoPc3) by the self-assembly of a zinc(ii) phthalocyanine substituted with hexadeca-sulphonates linked by hydrazone bonds for photoacoustic imaging and PTT. Due to the highly negative surface potential (-30.80 mV in water), NanoPc3 could effectively escape the phagocytosis of the reticuloendothelial system and be rapidly cleared from normal tissues, leading to little accumulation in the liver and excellent biosafety. The highly negatively-charged NanoPc3 changed into nearly neutral nanoparticles (NanoPc3H) under slightly acidic conditions, resulting in enhanced cellular uptake and retention time in tumor tissues. Moreover, the tumor of H22 tumor-bearing mice treated with NanoPc3 almost disappeared, suggesting an outstanding photothermal antitumor effect. NanoPc3 also hardly showed skin phototoxicity under irradiation. Its excellent antitumor effect and biosafety make NanoPc3 highly promising in clinical applications. This work will provide a new strategy for the design of tumor-targeted photothermal nanoagents with high biosafety.


Asunto(s)
Antineoplásicos/farmacología , Indoles/farmacología , Nanopartículas/química , Terapia Fototérmica , Zinc/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Indoles/química , Isoindoles , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/patología , Ratones , Estructura Molecular , Zinc/química
2.
J Photochem Photobiol B ; 213: 112086, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33232881

RESUMEN

With a view to developing highly efficient photosensitizers for both antitumor and antimicrobial photodynamic therapies, herein, we reported a super cationic zinc(II) phthalocyanine (Pc4), which was prepared through the quaternization of the N, N-dimethyl-3-aminophenoxyl-hexadeca-substituted precursor Pc3. Meanwhile, two disubstituted analogues (Pc1 and Pc2) were also prepared as controls. The cationic Pc2 and Pc4 had higher photoactivities including fluorescence and singlet oxygen than the neutral counterparts Pc1 and Pc3, probably because of the inhibition of intramolecular charge transfer (ICT) effect of the amino groups. With the bulky steric effect and high hydrophilicity, Pc4 presented non-aggregated behavior in aqueous solutions. Therefore, it exhibited the highest in vitro photodynamic activity toward HepG2 cancer cells with an IC50 value as low as 0.04 µM. Furthermore, Pc4 showed a highly efficient in vivo PDT effect on H22 tumor-bearing mice with 98.7% tumor growth inhibition. In addition, Pc4 also exhibited an excellent in vitro and in vivo photodynamic inactivation against S. aureus. The results indicate that the non-aggregated hexadeca-cationic Pc4 could serve as a promising photosensitizer for both antitumor and antimicrobial photodynamic therapies.


Asunto(s)
Antibacterianos/química , Antineoplásicos/síntesis química , Indoles/síntesis química , Compuestos Organometálicos/síntesis química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/síntesis química , Animales , Antibacterianos/farmacología , Antineoplásicos/farmacología , Cationes/química , Permeabilidad de la Membrana Celular , Transporte de Electrón , Femenino , Células Hep G2 , Humanos , Indoles/farmacología , Isoindoles , Ratones , Conformación Molecular , Neoplasias Experimentales , Compuestos Organometálicos/farmacología , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete/química , Espectrometría de Fluorescencia , Staphylococcus aureus/efectos de la radiación , Relación Estructura-Actividad , Compuestos de Zinc
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