MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Theranostics. 2022 May 16;12(9):4250-4268. doi: 10.7150/thno.68996. eCollection 2022.
Despite their outstanding properties in high surface-to-volume ratio and deep penetration, the application of ultrasmall nanoparticles for tumor theranostics remains limited because of their dissatisfied targeting performance and short blood circulation lifetime. Various synthetic materials with complex structures have been prepared as a multifunctional platform for loading ultrasmall nanoparticles. However, their use in nanomedicine is restricted because of unknown metabolic processes and potential physiological toxicity. Therefore, versatile and biocompatible nanoplatforms need to be designed through a simple yet effective method for realizing specific delivery and responsible release of ultrasmall nanoparticles. Iron-gallic acid coordination polymer nanodots (FeCNDs) exhibits outstanding photothermal ability and Fenton catalytic performance, which can be applied for tumor inhibition via hyperthermia and reactive oxygen species. A pH-responsive platelet-based hybrid membrane (pH-HCM) was prepared via co-extrusion and acted as a safe nanoplatform to load FeCNDs (pH-HCM@FeCNDs). Subsequently, their responsive performance and penetration ability were valued considering the multicellular sphere (MCS) model in an acidic or neutral environment. Thereafter, fluorescence image was performed to assess targeting capability of pH-HCM@FeCNDs. Finally, the corresponding antitumor and antimetastatic effects on orthotropic breast cancer were investigated. In 4T1 MCS model, pH-HCM@FeCNDs group exhibited higher penetration efficiency (72.84%) than its non-responsive counterparts (17.77%) under an acidic environment. Moreover, the fluorescence intensity in pH-HCM@FeCNDs group was 3.18 times higher than that in group without targeting performance in the fluorescence image experiment. Finally, through experiments, pH-HCM@FeCNDs was confirmed to exhibit the best antitumor effect (90.33% tumor reduction) and antimetastatic effects (only 0.29% tumor coverage) on orthotropic breast cancer. Hybrid cell membrane was an ideal nanoplatform to deliver nanodots because of its good responsibility, satisfactory targeting ability, and excellent biocompatibility. Consequently, this study provides novel insights into the delivery and release of nanodots in a simple but effect method.
尽管超小纳米粒子具有高的比表面积和深穿透的优异性质，但由于其靶向性能不佳和血液循环寿命短，它们在肿瘤治疗中的应用仍然受到限制。各种具有复杂结构的合成材料已被制备为装载超小纳米粒子的多功能平台。然而，由于未知的代谢过程和潜在的生理毒性，它们在纳米医学中的应用受到限制。因此，需要通过一种简单而有效的方法设计多功能和生物相容的纳米平台，以实现超小纳米粒子的特异性传递和负责释放。
铁-鞣酸配合物纳米点（FeCND）表现出优异的光热能力和 Fenton 催化性能，可通过高热和活性氧来抑制肿瘤。通过共挤出制备了一种 pH 响应性血小板基混合膜（pH-HCM），并用作装载 FeCND 的安全纳米平台（pH-HCM@FeCND）。随后，在酸性或中性环境下，考虑到多细胞球体（MCS）模型，评估了其响应性能和穿透能力。此后，通过荧光图像评估 pH-HCM@FeCND 的靶向能力。最后，研究了它们在原位乳腺癌中的抗肿瘤和抗转移作用。
在 4T1 MCS 模型中，在酸性环境下，pH-HCM@FeCND 组的穿透效率（72.84%）高于其无响应对照物（17.77%）。此外，在荧光图像实验中，pH-HCM@FeCND 组的荧光强度比无靶向性能的组高 3.18 倍。最后，通过实验证实，pH-HCM@FeCND 对原位乳腺癌具有最佳的抗肿瘤效果（肿瘤减少 90.33%）和抗转移效果（肿瘤覆盖率仅为 0.29%）。
混合细胞膜是一种理想的纳米载体，用于输送纳米点，因为它具有良好的响应性、令人满意的靶向能力和优异的生物相容性。因此，本研究为以简单但有效的方法输送和释放纳米点提供了新的思路。
