Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.
Enhanced antitumor activity of the photosensitizer meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate through encapsulation in antibody-targeted chitosan/alginate nanoparticles.
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DOI：
10.1021/bm301858a
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发表时间：
2013-02-11
影响因子：
6.2
通讯作者：
Scott, Christopher J.
中科院分区：
文献类型：
--
作者：
Abdelghany, Sharif M.;Schmid, Daniela;Deacon, Jill;Jaworski, Jakub;Fay, Francois;McLaughlin, Kirsty M.;Gormley, Julie A.;Burrows, James F.;Longley, Daniel B.;Donnelly, Ryan F.;Scott, Christopher J.
中位四甲（n -甲基-4-吡啶基）卟啉四甲磺酸（TMP）是一种光敏剂，可用于光动力治疗（PDT），通过在靶向肿瘤细胞中产生活性氧诱导细胞死亡。然而，TMP是高度亲水的，因此，它在细胞内积累的能力有限。在这项研究中，研究了一种通过将化合物包封在水凝胶基壳聚糖/海藻酸盐纳米颗粒配方中来提高TMP进入细胞的策略。制备了直径为560nm的纳米颗粒，每mg制剂包埋9.1 μg的TMP，并用细胞为基础进行了检测。这些颗粒被内吞到人类结直肠癌HCT116细胞中，并引起比游离药物更强的光细胞毒性作用。然后将靶向死亡受体5 （DR5）的抗体偶联到颗粒上，DR5是一种细胞表面凋亡诱导受体，在各种类型的癌症中上调，并在HCT116细胞中发现。结合抗体进一步增强了纳米颗粒的摄取和细胞毒性。综上所述，这些结果表明抗体偶联的壳聚糖/海藻酸盐纳米颗粒显著提高了包埋TMP的治疗效果。这种新方法为使用PDT治疗结直肠肿瘤提供了一种靶向部位特异性递送TMP和其他光敏剂药物的策略。
meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species in targeted tumor cells. However, TMP is highly hydrophilic, and therefore, its ability to accumulate intracellularly is limited. In this study, a strategy to improve TMP uptake into cells has been investigated by encapsulating the compound in a hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles of 560 nm in diameter entrapping 9.1 μg of TMP per mg of formulation were produced and examined in cell-based assays. These particles were endocytosed into human colorectal carcinoma HCT116 cells and elicited a more potent photocytotoxic effect than free drug. Antibodies targeting death receptor 5 (DR5), a cell surface apoptosis-inducing receptor up-regulated in various types of cancer and found on HCT116 cells, were then conjugated onto the particles. The conjugated antibodies further enhanced uptake and cytotoxic potency of the nanoparticle. Taken together, these results show that antibody-conjugated chitosan/alginate nanoparticles significantly enhanced the therapeutic effectiveness of entrapped TMP. This novel approach provides a strategy for providing targeted site-specific delivery of TMP and other photosensitizer drugs to treat colorectal tumors using PDT.
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DOI：
10.3390/molecules13092069
发表时间：
2008-09-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
d'Ayala GG;Malinconico M;Laurienzo P
通讯作者：
Laurienzo P
影响因子：
2.5
作者：
Arora, Saahil;Gupta, Sankalp;Budhiraja, Ramji D
通讯作者：
Budhiraja, Ramji D
影响因子：
8
作者：
Longley, DB;Wilson, TR;Johnston, PG
通讯作者：
Johnston, PG
影响因子：
3.6
作者：
Kaplan-Lefko, Paula J.;Graves, Jonathan D.;Gliniak, Brian C.
通讯作者：
Gliniak, Brian C.
影响因子：
10.8
作者：
Kocbek, Petra;Obermajer, Natasa;Kristl, Julijana
通讯作者：
Kristl, Julijana