Novel methods to incorporate photosensitizers into nanocarriers for cancer treatment by photodynamic therapy.
Novel methods to incorporate photosensitizers into nanocarriers for cancer treatment by photodynamic therapy.
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DOI：
10.1002/lsm.21113
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发表时间：
2011-09
影响因子：
2.4
通讯作者：
Pandey, Ravindra K.
中科院分区：
文献类型：
--
作者：
Wang, Shouyan;Fan, Wenzhe;Kim, Gwangseong;Hah, Hoe Jin;Lee, Yong-Eun Koo;Kopelman, Raoul;Ethirajan, Manivannan;Gupta, Anurag;Goswami, Lalit N.;Pera, Paula;Morgan, Janet;Pandey, Ravindra K.
将疏水光敏剂2-[1-己氧基乙基]-2-脱乙烯基焦脱镁叶绿酸-a（HPPH）通过3种不同的方法（包封、偶联和后负载）负载到无毒的可生物降解的胺功能化聚丙烯酰胺（AFPAA）纳米颗粒中，形成稳定的水分散体。每种制剂的理化性质以及光动力学性能进行了表征，以确定最有效的纳米载体制剂含有HPPH的光动力学治疗（PDT）。将HPPH或HPPH连接的丙烯酰胺加入到单体混合物中，并在微乳液中聚合，分别用于包封和缀合。对于后加载，将HPPH添加到预形成的纳米颗粒的水性悬浮液中。这些纳米颗粒进行了测试的光学特性，染料负载，染料浸出，粒度，单线态氧的生产，暗毒性，在体外光动力细胞杀伤，全身荧光成像和体内PDT。HPPH被成功地封装、缀合或后负载到AFPAA纳米颗粒中。所得纳米颗粒为球形，平均直径为29 ± 3 nm。HPPH在包封后保持完整，并且对于所有三种制剂，从纳米颗粒浸出的HPPH可忽略不计。最高的单线态氧产量是通过后加载制剂实现的，其在体外测定中引起最高的光毒性。未观察到暗毒性。后加载HPPH AFPAA纳米颗粒定位于小鼠结肠癌模型中的肿瘤，使荧光成像，并产生类似的光动力肿瘤反应的游离HPPH在等效剂量。后负载是一种很有前途的方法，用于将疏水光敏剂负载到纳米颗粒上，以实现有效的体外和体内PDT。Lasers Surg. Med. 43：686-695，2011.
A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. Lasers Surg. Med. 43:686–695, 2011.
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