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基于光敏明胶的水凝胶的合成与表征及其在 HeLa-CCL2 细胞系的光动力疗法中的应用。

Synthesis and characterization of photosensitive gelatin-based hydrogels for photodynamic therapy in HeLa-CCL2 cell line.

机构信息

Research and Development Institute - IPD, Vale do Paraíba University - UNIVAP, Av. Shishima Hifumi, 2911., São José dos Campos, SP CEP 12244-000, Brazil.

Research and Development Institute - IPD, Vale do Paraíba University - UNIVAP, Av. Shishima Hifumi, 2911., São José dos Campos, SP CEP 12244-000, Brazil.

出版信息

Photodiagnosis Photodyn Ther. 2022 Jun;38:102818. doi: 10.1016/j.pdpdt.2022.102818. Epub 2022 Mar 22.

DOI:10.1016/j.pdpdt.2022.102818
PMID:35331952
Abstract

BACKGROUND

Hydrogel systems are increasingly gaining visibility involving biomedicine, tissue engineering, environmental treatments, and drug delivery systems. These systems have a three-dimensional network composition and high-water absorption capacity, are biocompatible, allowing them to become an option as photosensitizer carriers (PS) for applications in Photodynamic Therapy (PDT) protocols.

METHODS

A nanohydrogel system (NAHI), encapsulated with chloroaluminium phthalocyanine (ClAlPc) was synthesized for drug delivery.. NAHI was synthesized using gelatin as based polymer by the chemical cross-linking technique. The drug was encapsulated by immersing the hydrogel in a 1.0 mg.mL ClAlPc solution. The external morphology of NAHI was examined by scanning electron microscopy (SEM). The degree of swelling of the synthesized system was evaluated to determine the water absorption potential. The produced nanohydrogel system was characterized by photochemical, photophysical and photobiologial studies.

RESULTS

The images from the SEM analysis showed the presence of three-dimensional networks in the formulation. The swelling test demonstrated that the nanohydrogel freeze-drying process increases its water holding capacity. All spectroscopic results showed excellent photophysical parameters of the drug studied when served in the NAHI system. The incorporation efficiency was 70%. The results of trypan blue exclusion test have shown significant reduction (p < 0.05) in the cell viability for all groups treated with PDT, in all concentrations tested. In HeLa cells, PDT mediated by 0,5 mg.mL ClAlPc encapsulated in NAHI showed a decrease in survival close to 95%. In the internalization cell study was possible to observe the internalization of phthalocyanine after one hour of incubation, at 37 °C, with the the accumulation of PS in the cytoplasm and inside the nucleus at both concentrations tested.

CONCLUSIONS

Given the peculiar performance of the selected system, the resulting nanohydrogel is a versatile platform and display potential applications as controlled delivery systems of photosensitizer for photodynamic therapy application.

摘要

背景

水凝胶系统在生物医学、组织工程、环境处理和药物输送系统等领域的应用日益受到关注。这些系统具有三维网络结构和高吸水性,生物相容性好,因此成为光敏剂载体(PS)用于光动力疗法(PDT)方案的选择。

方法

合成了一种纳米水凝胶系统(NAHI),用于药物输送,该系统包裹了氯铝酞菁(ClAlPc)。NAHI 是通过化学交联技术以明胶为基础聚合物合成的。通过将水凝胶浸入 1.0mg.mL ClAlPc 溶液中,实现药物的封装。通过扫描电子显微镜(SEM)观察 NAHI 的外部形态。评估合成系统的溶胀程度,以确定其吸水潜力。通过光化学、光物理和光生物研究对所制备的纳米水凝胶系统进行了表征。

结果

SEM 分析图像显示配方中存在三维网络。溶胀试验表明,纳米水凝胶冻干过程增加了其保水能力。所有光谱结果均表明,当药物在 NAHI 系统中使用时,其具有优异的光物理参数。包封效率为 70%。台盼蓝排除试验结果表明,所有接受 PDT 治疗的组在所有测试浓度下,细胞活力均显著降低(p<0.05)。在 HeLa 细胞中,由 0.5mg.mL ClAlPc 包封在 NAHI 中介导的 PDT 显示接近 95%的存活率下降。在细胞内化研究中,在 37°C 孵育 1 小时后,可以观察到酞菁的内化,并且在两种测试浓度下,PS 都在细胞质和核内积累。

结论

鉴于所选系统的特殊性能,所得纳米水凝胶是一种多功能平台,具有作为光敏剂控释系统用于光动力治疗应用的潜力。

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