Enling Chang1,2, Jiachuan Bu1, Lili Ding1, Jenny W H Lou1,3, Michael S Valic1,2, Miffy H Y Cheng1, Véronique Rosilio4, Juan Chen5, Gang Zheng6,7,8. 1. Princess Margaret Cancer Centre, University Health Network, PMCRT 5-353, 101 College Street, Toronto, ON, M5G 1L7, Canada. 2. Institute of Biomedical Engineering, University of Toronto, PMCRT 5-354, 101 College Street, Toronto, ON, M5G 1L7, Canada. 3. Department of Medical Biophysics, University of Toronto, Toronto, Canada. 4. Institut Galien Paris-Saclay, Université Paris-Saclay, CNRS, Châtenay-Malabry, France. 5. Princess Margaret Cancer Centre, University Health Network, PMCRT 5-353, 101 College Street, Toronto, ON, M5G 1L7, Canada. juan.chen@uhnresearch.ca. 6. Princess Margaret Cancer Centre, University Health Network, PMCRT 5-353, 101 College Street, Toronto, ON, M5G 1L7, Canada. gang.zheng@uhnres.utoronto.ca. 7. Institute of Biomedical Engineering, University of Toronto, PMCRT 5-354, 101 College Street, Toronto, ON, M5G 1L7, Canada. gang.zheng@uhnres.utoronto.ca. 8. Department of Medical Biophysics, University of Toronto, Toronto, Canada. gang.zheng@uhnres.utoronto.ca.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. RESULTS: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. CONCLUSION: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.
Entities:
Keywords:
Cancer therapy; Chemotherapy; Drug delivery; Nanoparticle; Paclitaxel; Photodynamic therapy; Porphyrin
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