Radiation-induced photodynamic therapy using calcium tungstate nanoparticles and 5-aminolevulinic acid prodrug
Radiation-induced photodynamic therapy using calcium tungstate nanoparticles and 5-aminolevulinic acid prodrug
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DOI：
10.1039/d3bm00921a
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发表时间：
2023-08-02
影响因子：
6.6
通讯作者：
Won，You-Yeon
中科院分区：
文献类型：
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作者：
Viswanath，Dhushyanth;Shin，Sung-Ho;Won，You-Yeon
使用5-氨基乙酰丙酸（ALA）前药的光动力疗法（PDT）是一种经过临床试验和验证的表面病变治疗方式。然而，由于激活由ALA代谢产生的光敏剂原卟啉IX（PPIX）所需的可见光的穿透深度差，其用于深部肿瘤受到限制。本文报道了聚乙二醇-b-乳酸（PEG-PLA）包裹的钨酸钙（CaWO 4，简称CWO）纳米粒子（PEG-PLA/CWO NPs）作为能量转换器用于ALA的X射线激活PDT。由于CWO核提供的放射性发光与PPIX的吸光度之间的光谱重叠，这些NP可以在放射治疗（RT）期间用作原位可见光激活源，从而减轻穿透深度的限制。我们证明了这种效应在具有不同放射敏感性的不同细胞系中观察到。重要的是，PPIX和PEG-PLA/CWO NP在不存在辐射的情况下在治疗剂量下均不表现出显著的毒性。为了评估这种方法的有效性，我们使用皮下植入固有抗辐射4 T1肿瘤的同基因小鼠模型进行了一项研究。结果显示，与常规RT相比，即使仅使用2次4戈伊X射线，预后也显著改善。综上所述，这些结果表明，PEG-PLA/CWO纳米颗粒是在深层肿瘤中应用ALA-PDT的有前途的药物，从而显著扩展了已经建立的治疗策略的效用。
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) prodrug is a clinically tried and proven treatment modality for surface-level lesions. However, its use for deep-seated tumors has been limited due to the poor penetration depth of visible light needed to activate the photosensitizer protoporphyrin IX (PPIX), which is produced from ALA metabolism. Herein, we report the usage of poly(ethylene glycol-b-lactic acid) (PEG–PLA)-encapsulated calcium tungstate (CaWO4, CWO for short) nanoparticles (PEG–PLA/CWO NPs) as energy transducers for X-ray-activated PDT using ALA. Owing to the spectral overlap between radioluminescence afforded by the CWO core and the absorbance of PPIX, these NPs can serve as an in situ visible light activation source during radiotherapy (RT), thereby mitigating the limitation of penetration depth. We demonstrate that this effect is observed across different cell lines with varying radio-sensitivity. Importantly, both PPIX and PEG–PLA/CWO NPs exhibit no significant toxicities at therapeutic doses in the absence of radiation. To assess the efficacy of this approach, we conducted a study using a syngeneic mouse model subcutaneously implanted with inherently radio-resistant 4T1 tumors. The results show a significantly improved prognosis compared to conventional RT, even with as few as 2 fractions of 4 Gy X-rays. Taken together, these results suggest that PEG–PLA/CWO NPs are promising agents for application of ALA-PDT in deep-seated tumors, thereby significantly expanding the utility of the already established treatment strategy.