Princess Margaret Cancer Centre, University Health Network, PMCRT 5-353, 101 College Street, Toronto, ON, M5G 1L7, Canada.
Institute of Biomedical Engineering, University of Toronto, PMCRT 5-354, 101 College Street, Toronto, ON, M5G 1L7, Canada.
J Nanobiotechnology. 2021 May 25;19(1):154. doi: 10.1186/s12951-021-00898-1.
Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform.
PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core-shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning.
PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment.
卟啉脂质是多功能的构建模块，可实现癌症的治疗诊断一体化，已被应用于创建多种多模式纳米颗粒平台，包括类似脂质体的卟啉体（水核）、卟啉纳米液滴（液化气体核）和超小卟啉脂蛋白。在这里，我们使用卟啉脂质来稳定水/油界面，从而在油核中负载紫杉醇来创建载有紫杉醇的卟啉脂质纳米乳剂（PLNE-PTX），便于在一个平台上结合光动力疗法（PDT）和化学疗法。
PTX（3.1wt%）和卟啉（18.3wt%）被有效地负载到 PLNE-PTX 中，形成直径为 120nm 的球形核壳纳米乳剂。PLNE-PTX 在系统输送中表现出稳定性，导致 KB 肿瘤荷瘤小鼠中的肿瘤积累量高达 5.4 ID%/g。PLNE-PTX 联合治疗以相加的方式抑制肿瘤生长（78%），与 PDT 单药治疗（44%）或化疗（46%）相比，在治疗后 16 天。此外，PLNE-PTX 联合治疗平台中 PTX 剂量减少四倍（1.8mgPTX/kg），与剂量为 7.2mgPTX/kg 的 Taxol 相比，显示出更好的治疗效果，可减少副作用。此外，PLNE-PTX 的固有荧光可实时跟踪纳米颗粒到达肿瘤，有助于治疗计划。
PLNE-PTX 在单一平台上将 PDT 和化学疗法联合起来，可获得更好的抗肿瘤效果，并有可能减少与单一化学疗法相关的副作用。PLNE-PTX 的固有成像方式能够实时跟踪，并允许时空调节，以改善癌症治疗。
