Park In-Kyu, Ju Do-Bin, Babu Amal, Lee Jeong-Cheol, Pyung Young Jin, Cho Chong-Su, Kim Hyun-Joong
Department of Biomedical Sciences, BK21 PLUS Center for Creative Biomedical Scientists, Chonman National University Medical School, Gwangju, 61469, South Korea.
Department of Agricultural Biotechnology, Seoul National University, Seoul, 08824, South Korea.
Biomater Res. 2022 Jun 27;26(1):28. doi: 10.1186/s40824-022-00273-7.
Combination therapies comprising multiple methods, such as photodynamic therapy have been applied to be complements chemotherapy as they increase the therapeutic efficiency by enabling the intelligent drug delivery to target sites by exposing the photosensitizer to light and activating it in the tumor tissue. This study evaluated in vitro photodynamic therapy of methylene blue (MB)-loaded acetyl resistant starch (ARS) nanoparticles (NPs).
ARS was synthesized by the reaction between resistant starch (RS) and acetic anhydride. MB-loaded ARS NPs and ARS NPs were prepared by a single emulsion method. Synthesized ARS was measured by NMR. Prepared ARS NPs and MB-loaded ARS NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction, UV/Vis, and circular dichroism (CD). MB-loaded ARS NPs were treated in mouse colon cancer cells (CT-26) and they were treated under near-infrared (NIR) laser irradiation.
Synthesis of ARS was confirmed by NMR and the degree of substitutions in the ARS was 7.1. The morphologies of ARS NPs observed by TEM were spherical shapes and the particle sizes of ARS NPs were 173.4 nm with a surface charge of - 17.24 mV. The d-spacing of ARS NPs was smaller than those of RS and the conformational changes of RS occurred by the formation of self-assembled polymeric NPs with induction of CD of the MB by chiral ARS NPs. The phototoxicity of CT-26 cells treated by MB-loaded ARS NPs dramatically decreased in a dose-dependent manner under NIR laser irradiation compared to free MB.
This study demonstrated the ordered nanosized structures in the ARS NPs and conformational change from random coil structure of RS to alpha-helices one of ARS occurred and CD of the achiral MB was induced. The MB-loaded ARS NPs showed a higher generation of reactive oxygen species (ROS) in the CT-26 cells than free MB with the NIR laser irradiation and resulting in phototoxicity under irradiation.
包括光动力疗法等多种方法的联合疗法已被应用以补充化疗，因为它们通过将光敏剂暴露于光并在肿瘤组织中激活它，从而实现智能药物递送至靶位点，提高了治疗效率。本研究评估了负载亚甲蓝（MB）的乙酰化抗性淀粉（ARS）纳米颗粒（NPs）的体外光动力疗法。
通过抗性淀粉（RS）与乙酸酐反应合成ARS。采用单乳液法制备负载MB的ARS NPs和ARS NPs。通过核磁共振（NMR）测定合成的ARS。通过透射电子显微镜（TEM）、动态光散射（DLS）、X射线衍射、紫外/可见光谱和圆二色性（CD）对制备的ARS NPs和负载MB的ARS NPs进行表征。将负载MB的ARS NPs作用于小鼠结肠癌细胞（CT-26），并在近红外（NIR）激光照射下进行处理。
通过NMR证实了ARS的合成，ARS中的取代度为7.1。通过TEM观察到ARS NPs的形态为球形，ARS NPs的粒径为173.4 nm，表面电荷为-17.24 mV。ARS NPs的d间距小于RS的d间距，并且通过手性ARS NPs诱导MB的CD形成自组装聚合物NPs，导致RS的构象发生变化。与游离MB相比，在NIR激光照射下，负载MB的ARS NPs处理的CT-26细胞的光毒性以剂量依赖性方式显著降低。
本研究证明了ARS NPs中有序的纳米结构，并且发生了从RS的无规卷曲结构到ARS的α-螺旋结构的构象变化，并且诱导了非手性MB的CD。在NIR激光照射下，负载MB的ARS NPs在CT-26细胞中比游离MB产生更高的活性氧（ROS），并在照射下导致光毒性。
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