Nucleus-Targeted Photosensitizer Nanoparticles for Photothermal and Photodynamic Therapy of Breast Carcinoma

Abstract

Purpose The near-infrared fluorescent dye indocyanine green (ICG) has shown great potential in the photodynamic therapy (PDT) and photothermal therapy (PTT) of cancer. However, its disadvantages of instability in aqueous solution, short half-life, and non-targeting accumulation limit the effectiveness of ICG PDT/PTT. To overcome the disadvantages of ICG in tumor treatment, we designed PEGylated-human serum albumin (PHSA)-ICG-TAT. In this nanoparticle, PEG4000, the HSA package, and nuclear targeting peptide TAT (human immunodeficiency virus 1 [HIV-1]-transactivator protein) were used to improve the water solubility of ICG, prolong the life span of ICG in vivo, and target the nuclei of tumor cells, respectively. Methods The PHSA-ICG-TAT was characterized in terms of morphology and size, ultraviolet spectrum, dispersion stability, singlet oxygen and cellular uptake, and colocalization using transmission electron microscopy and dynamic light scattering, and fluorescence assay, respectively. Subsequently, the anti-tumor effect of PHSA-ICG-TAT was investigated via in vitro and in vivo experiments, including cell viability, apoptosis, comet assays, histopathology, and inhibition curves. Results The designed ICG-loaded nanoparticle had a higher cell uptake rate and stronger PDT/PTT effect than free ICG. The metabolism of PHSA-ICG-TAT in normal mice revealed that there was no perceptible toxicity. In vivo imaging of mice showed that PHSA-ICG-TAT had a good targeting effect on tumors. PHSA-ICG-TAT was used for the phototherapy of tumors, and significantly suppressed the tumor growth. The tumor tissue sections showed that the cell gap and morphology of the tumor tissue had been obviously altered after treatment with PHSA-ICG-TAT. Conclusion These results indicate that the PHSA-ICG-TAT had a significant therapeutic effect against tumors.

Biopolímeros: Aplicaciones de andamios en medicina regenerativa

“…Gracias a su fácil segregación y procedimiento permite una multifincionalidad al modificar un polielectrolito mediante la agregación de polímeros, nanopartículas orgánicas o incluso nanotubos de carbono (Karabasz, Bzowska, & Szczepanowicz, 2020). Su avance durante los últimos años ha permitido la creación de sistemas de administración de fármacos multifuncionales por sus condiciones, en donde se puede desarrollar una incorporación de la proteína objetivo a un direccionamiento de anticuerpos presentes sobre la célula objetivo manteniendo un ambiente controlado, otra aplicación recae en el uso de nanopartículas magnéticas que interactúan sobre un campo magnético externo generado por un nanoportador productor de cargas eléctricas, este tipo de atracción ha permitido la investigación celular en la reparación de tejidos, administración de fármacos, imágenes de resonancia magnética (Liu, et al, 2021;Gomha, et al, 2021).…”

Dual-Target Multifunctional Superparamagnetic Cationic Nanoliposomes for Multimodal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy of Retinoblastoma

“…With low afford and high biosafety, ICG has often been used in fundus choroidal angiography 23 and commonly acted as a good photoacoustic imaging agent in many studies. 24 , 25 In addition to imageology functions, it is noteworthy that ICG also has excellent photothermal/photodynamic properties under the same excitation laser. 26 Given the limited photodynamic effects of ICG caused by hypoxia in the tumor microenvironment, PFH is considered an excellent option to remedy the deficiency.…”

Polymer encapsulated clinical ICG nanoparticles for enhanced photothermal therapy and NIR fluorescence imaging in cervical cancer

“…24,25 Under laser irradiation, the ICG also produces photodynamic (PDT) effects, therefore PDT and PTT are oen combine used. [26][27][28][29] Nevertheless, researchers were more inclined to study ICG-based PTT since ICG produces stronger photothermal effect. Besides, the poor optical and thermal stability of ICG as PTN limited its further applications.…”

“…[27][28][29] Studies have shown that the polymer encapsulated clinical ICG nanoparticles can not only increase the stability of nanoparticles, but also could enhance PDT/PTT effect, meanwhile strengthen biocompatibility of the NPs with negligible toxicity. [27][28][29] Poly(styrene-co-maleic anhydride) (PSMA) is an amphiphilic polymer 40 and oen selected as encapsulation matrix for organic dyes to increase their chemical stability and biocompatibility. [41][42][43][44][45] In addition, PSMA has been used clinically and its covalent binding to proteins has been studied.…”

“…Also, ICG@PSMA NPs showed good PTT property in cervical cancer cells as PTN under 808 nm laser irradiation with PTT efficiency of $70%. Besides, ICG@PSMA NPs [27][28][29] have great potentials in other different types of cancer. Therefore, ICG@PSMA NPs have great potentials as PTN for tumor therapy, and our results can provide a good basis for following in vivo experiments.…”