Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.

中文翻译：

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负载锌酞菁的细胞外囊泡提高光动力疗法在结肠癌共培养和临床前模型中的有效性和选择性

光动力疗法 (PDT) 是一种很有前途的临床批准的癌症治疗方法。然而，PDT 的疗效往往受到光敏剂 (PS) 对恶性肿瘤的选择性和分布差的限制，导致皮肤光敏反应时间延长。在这项工作中，我们提出了一种简单而直接的策略，通过在纯化的、自然分泌的细胞外囊泡 (EV) 中稳定来增加亲脂性 PS 酞菁锌 (ZnPc) 在结肠癌中的肿瘤分布、选择性和功效。PS ZnPc 通过不影响尺寸分布或表面电荷的直接孵化策略纳入 EV（EV-ZnPc）。通过使用模拟肿瘤微环境的共培养模型，与巨噬细胞和树突细胞相比，我们确定了 EV-ZnPc 对结肠癌细胞的优先摄取。我们观察到 PDT 促进了正常细胞和免疫细胞中的总肿瘤细胞死亡，但在共培养模型中显示出对癌细胞的选择性。体内试验表明，在单次静脉内或瘤内注射后，EV-ZnPc 能够靶向肿瘤细胞并在 15 天内强烈减少肿瘤生长。这些数据揭示了使用简单的非合成策略来增强 PDT 的潜力和功效的机会，这些策略可能有助于转化为临床实践。体内试验表明，在单次静脉内或瘤内注射后，EV-ZnPc 能够靶向肿瘤细胞并在 15 天内强烈减少肿瘤生长。这些数据揭示了使用简单的非合成策略来增强 PDT 的潜力和功效的机会，这些策略可能有助于转化为临床实践。体内试验表明，在单次静脉内或瘤内注射后，EV-ZnPc 能够靶向肿瘤细胞并在 15 天内强烈减少肿瘤生长。这些数据揭示了使用简单的非合成策略来增强 PDT 的潜力和功效的机会，这些策略可能有助于转化为临床实践。