Photodynamic therapy (PDT) with photosensitizers has been considered an effective strategy for treating tumors by generating reactive oxygen species (ROS) to induce tumor cells apoptosis or necrosis. However, the poor water solubility, rapid blood clearance, and lack of effective targeting of the photosensitizer are still a serious challenge for its satisfactory anti-cancer efficacy. Herein, we fabricated a stem cell membrane–camouflaged gelatin nanogels (Ng), which integrating the drug loading capacity of Ng and targeting ability of stem cell membrane, endowed with many unique advantages for targeted drug delivery. This bioinspired drug delivery system composed of hydrophobic photosensitizer, chlorin e6 (Ce6)-loaded gelatin nanogels (Ng) (Ng/Ce6), as the inner cores and coated stem cell membrane vesicles (SCV) as the outer shells, noted as Ng/Ce6@SCV. The averaged hydrodynamic diameter of Ng/Ce6@SCV was 202.7 ± 11.7 nm (polydispersity index (PDI) = 0.113). Ng/Ce6@SCV could efficiently promote the cellular internalization of Ce6, and generate enough ROS in the tumor cells after near infrared (NIR) laser irradiation, which could efficiently suppress the growth of A549 tumor cells in vitro. After administration, Ng/Ce6@SCV exhibited targeting accumulation and long-term retention at tumor tissues, which was related to the immune escape and tumor targeting ability of the stem cell membrane. The in vivo anti-tumor activity results also demonstrated the enhanced anti-tumor effect of Ng/Ce6@SCV after NIR irradiation by significantly suppressed the primary tumor growth with minimal side effects. All the results indicated this polyphosphoester-based bioinspired nanodrug delivery system could be a suitable strategy for precise and effective PDT of cancers.

通过产生活性氧（ROS）诱导肿瘤细胞凋亡或坏死，使用光敏剂进行光动力疗法（PDT）被认为是治疗肿瘤的有效策略。然而，差的水溶性，快速的血液清除和缺乏光敏剂的有效靶向仍然是其令人满意的抗癌功效的严重挑战。在此，我们制造了一种伪装成干细胞膜的明胶纳米凝胶（Ng），该凝胶整合了Ng的载药量和干细胞膜的靶向能力，并具有靶向药物递送的许多独特优势。这种生物启发性的药物传递系统由疏水性光敏剂，载有二氢卟酚e6（Ce6）的明胶纳米凝胶（Ng）（Ng / Ce6）组成，并以外壳为涂层的干细胞膜囊泡（SCV）组成，记为Ng / Ce6 @ SCV。Ng / Ce6 @ SCV的平均流体动力学直径为202.7±11.7 nm（多分散指数（PDI）= 0.113）。Ng / Ce6 @ SCV可以有效促进Ce6的细胞内在化，并在近红外（NIR）激光照射后在肿瘤细胞中产生足够的ROS，从而可以有效地抑制A549肿瘤细胞的体外生长。给药后，Ng / Ce6 @ SCV在肿瘤组织中表现出靶向积累和长期保留，这与干细胞膜的免疫逃逸和肿瘤靶向能力有关。体内抗肿瘤活性结果还证明了Ng照射后Ng / Ce6 @ SCV的增强的抗肿瘤作用通过显着抑制了原发性肿瘤的生长而具有最小的副作用。