Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City 32001, Taiwan R.O.C.
Department of Chemical and Materials Engineering, National Central University, Taoyuan City 32001, Taiwan R.O.C.
ACS Biomater Sci Eng. 2024 Oct 14;10(10):6332-6343. doi: 10.1021/acsbiomaterials.4c01150. Epub 2024 Sep 12.
Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 μM ICG/CPT, MICFNS + NIR can provide comparable cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents . Moreover, the MICFNS with 40/10 μM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.
光化疗已被公认为癌症治疗的一种很有前途的联合治疗方法。然而，药物靶向递送、全身毒性和肿瘤微环境的缺氧性质等困难仍然阻碍了其应用。为了克服这些挑战，本研究开发了一种具有吲哚菁绿（ICG）和喜树碱（CPT）的氟辛烷溴（PFOB）双层纳米聚合物囊泡，命名为 MICFNS，以黑色素瘤为模型，用于 MICFNS 的制造和治疗应用。我们的数据表明，MICFNS 能够稳定纳米载体中的 ICG 和 CPT，并由于黑色素瘤膜介导的同源性，能够被 B16F10 细胞快速内化。在近红外照射下，由于 PFOB 的掺入，MICFNS 可以引发热疗并提供增强的单线态氧产生。当 ICG/CPT 浓度≥10/2.5 μM 时，MICFNS + NIR 可以提供与单独使用 8 倍高剂量封装 CPT 相当的抗癌效果。通过动物研究，我们进一步证明 MICFNS 可以迅速到达肿瘤部位，并且比游离药物具有更长的保留时间。此外，与 30 s 近红外照射相结合的 40/10 μM ICG/CPT 的 MICFNS 可以成功抑制肿瘤生长，而在 14 天的治疗过程中没有全身毒性。我们推测，这种抗肿瘤作用是通过光疗和化疗联合实现的，MICFNS 通过两步杀瘤过程发挥作用。综上所述，我们预计 MICFNS 作为一种光化疗纳米平台，具有在临床癌症治疗中应用的巨大潜力。
