Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy
Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy
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DOI：
10.1039/c6bm00011h
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发表时间：
2016-01-01
影响因子：
6.6
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Nomoto, Takahiro;Fukushima, Shigeto;Kataoka, Kazunori
光动力疗法（PDT）是一种具有光选择性的恶性肿瘤治疗方法。为了提高PDT的疗效，人们开发了多种纳米载体，将光敏剂（ps）选择性地通过泄漏的肿瘤相关血管输送到肿瘤中。然而，纳米载体在血液中相应的长时间滞留可能导致对正常组织（如皮肤）不利的光化学损伤。在这里，我们报道了一种有机-无机杂化纳米载体，其PDT效率具有ph响应的开关。该杂化纳米载体由钙/磷酸盐离子、氯e6（两亲性低分子量PS）和聚乙二醇-b-聚天冬氨酸（PEG-PAsp）共聚物在水溶液中简单混合而成。该杂化纳米载体采用磷酸钙（CaP）芯包裹聚乙二醇（PEG）屏蔽层。在生理条件下（pH 7.4），纳米载体通过降低氧分子对纳入的PS的通路来抑制PS的光化学活性，而由于CaP的溶解和最终恢复氧气和PS之间的通路，PDT的效果以pH响应的方式恢复。由于这种开关，纳米载体减少了血液中的光化学损伤。同时，它在肿瘤细胞内诱导有效的PDT效果，以响应内切酶/溶酶体的酸性条件。
Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors in a light-selective manner. To improve the PDT efficacy, numerous kinds of nanocarriers have been developed to deliver photosensitizers (PSs) selectively into the tumor through leaky tumor-associated vasculature. However, the corresponding prolonged retention of the nanocarrier in the bloodstream may lead to unfavorable photochemical damage to normal tissues such as skin. Here, we report an organic-inorganic hybrid nanocarrier with a pH-responsive on/off switch of PDT efficacy. This hybrid nanocarrier is constructed by hydrothermal synthesis after simple mixing of calcium/phosphate ions, chlorin e6 (amphiphilic low molecular weight PS), and poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) copolymers in an aqueous solution. The hybrid nanocarrier possesses a calcium phosphate (CaP) core encapsulating the PSs, which is surrounded by a PEG shielding layer. Under physiological conditions (pH 7.4), the nanocarrier suppressed the photochemical activity of PS by lowering the access of oxygen molecules to the incorporated PS, while PDT efficacy was restored in a pH-responsive manner because of the dissolution of CaP and eventual recovery of access between the oxygen and the PS. Owing to this switch, the nanocarrier reduced the photochemical damage in the bloodstream, while it induced effective PDT efficacy inside the tumor cell in response to the acidic conditions of the endo-/lysosomes.