HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.
HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.
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结合 5-氨基乙酰丙酸的 HPMA 共聚物在具有肿瘤响应和靶向特性的光动力疗法中表现出卓越的功效。
DOI：
10.1016/j.nano.2022.102636
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Fang J.
中科院分区：
文献类型：
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作者：
Islam R;Kotalik K;Subr V;Gao S;Zhou J-R;Yokomizo K;Etrych T;Fang J.
在这项研究中，我们开发了一种用于肿瘤靶向光动力治疗的5-氨基乙酰丙酸（5-ALA）纳米配方，其中5-ALA通过腙键（即P-ALA）与生物相容性聚合物n -（2-羟丙基）甲基丙烯酰胺（HPMA）偶联。P-ALA在水溶液中表现为纳米级分子，平均尺寸为5.5 nm。P-ALA在酸性pH下的释放速率明显高于生理pH，说明其在酸性肿瘤环境下具有快速释放的特点。当P-ALA浓度达到0.1 mg/ml时，未表现出明显的细胞毒性，但在光照下，20 ~ 30 μg/ml的ic50浓度可诱导细胞明显死亡。更重要的是，我们发现P-ALA的肿瘤蓄积量明显高于5-ALA，这得益于其纳米尺寸，利用了增强的渗透性和滞留性（EPR）效应。因此，P-ALA在体内抗肿瘤效果明显提高，且无明显副作用。因此，我们期望P-ALA作为纳米光敏剂用于抗癌光动力治疗。
In this study, we developed a nanoformulation of 5-aminolevulinic acid (5-ALA) for tumor-targeted photodynamic therapy, in which 5-ALA was conjugated with a biocompatible polymerN-(2-hydroxypropyl)methacrylamide (HPMA) through the hydrazone bond, i.e., P-ALA. P-ALA behaves as the nano-sized molecule with an average size of 5.5 nm in aqueous solution. P-ALA shows a largely increased release rate in acidic pH than physiological pH, suggesting the rapid release profile in acidic tumor environment. P-ALA did not show apparent cytotoxicity up to 0.1 mg/ml, however, under light irradiation, remarkable cell death was induced with the IC50of 20–30 μg/ml. More importantly, we found significantly higher tumor accumulation of P-ALA than 5-ALA which benefit from its nano-size by taking advantage of the enhanced permeability and retention (EPR) effect. Consequently, P-ALA exhibited much improved in vivo antitumor efficacy without any apparent side effects. We thus anticipate the application of P-ALA as a nano-designed photosensitizer for anticancer photodynamic therapy.