Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising therapeutic strategy for cancer treatment. In this study, we synthesized a pHPMA conjugated pyropheophorbide-a (P-PyF) as a cancer theranostic agent for PDT and photodynamic diagnostics (PDD). Pyropheophorbide-a has one carboxyl group which was conjugated to pHPMA via amide bond yielding the intended product with high purity. In aqueous solutions, P-PyF showed a mean particle size of ∼200 nm as it forms micelle which exhibited fluorescence quenching and thus very little singlet oxygen (¹O₂) production. In contrast, upon disruption of micelle strong fluorescence and ¹O₂ production were observed. In vitro study clearly showed the PDT effect of P-PyF. More potent ¹O₂ production and PDT effect were observed during irradiation at ∼420 nm, the maximal absorbance of pyropheophorbide-a, than irradiation at longer wavelength (i.e., ∼680 nm), suggesting selection of proper absorption light is essential for successful PDT. In vivo study showed high tumor accumulation of P-PyF compared with most of normal tissues due to the enhanced permeability and retention (EPR) effect, which resulting in superior antitumor effect under irradiation using normal xenon light source of endoscope, and clear tumor imaging profiles even in the metastatic lung cancer at 28 days after administration of P-PyF. On the contrary irradiation using long wavelength (i.e., ∼680 nm), the lowest Q-Band, exhibited remarkable tumor imaging effect with little autofluorescence of background. These findings strongly suggested P-PyF may be a potential candidate-drug for PDT/PDD, particularly using two different wavelength for treatment and detection/imaging, respectively.

使用聚合物光敏剂的肿瘤靶向光动力疗法（PDT）是一种有前途的癌症治疗策略。在这项研究中，我们合成了pHPMA共轭焦脱镁叶绿酸-a（P-PyF）作为PDT和光动力诊断（PDD）的癌症治疗药物。焦脱镁叶绿酸-a具有一个羧基，该羧基通过酰胺键与pHPMA缀合，从而得到具有高纯度的目标产物。在水溶液中，P-PyF形成胶束时表现出约200 nm的平均粒径，该胶束表现出荧光猝灭作用，因此几乎不产生单线态氧（¹ O ₂）。相反，在破坏胶束时，强烈的荧光和¹ O ₂观察生产。体外研究清楚地表明了P-PyF的PDT效应。更有效的¹ Ò ₂在~420纳米，最大吸光度的照射过程中观察生产和PDT效果焦-A，比在较长波长（即，~680纳米），适当的吸收光的提示选择照射是成功PDT必不可少。体内研究显示，由于增强的通透性和保留（EPR）效应，与大多数正常组织相比，P-PyF具有较高的肿瘤蓄积性，从而在使用内窥镜的普通氙气光源照射下具有优异的抗肿瘤作用，甚至在正常情况下也能获得清晰的肿瘤影像给予P-PyF后28天时转移性肺癌。相反，使用长波长（约680 nm）的最低Q波段辐射显示出显着的肿瘤成像效果，而背景的自发荧光很少。这些发现强烈表明，P-PyF可能是PDT / PDD的潜在候选药物，特别是分别使用两种不同的波长进行治疗和检测/成像。