Photodynamic therapy(PDT)is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent chemotherapy.Previously,we demonstrated that liposomes containing a bilayer-anchored photosensitiz...Photodynamic therapy(PDT)is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent chemotherapy.Previously,we demonstrated that liposomes containing a bilayer-anchored photosensitizer(porphyrin-phospholipid;PoP)can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with red-light.In the present work,we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of liposomes.Cabazitaxel(CTX)is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar%PoP,generating CTX-loaded PoP liposomes(CTX-PoP-Lip).CTX-PoP-Lip showed unilamellar vesicle morphology,and exhibited integrity in storage and serum,while maintaining drug stability under laser irradiation.In vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip,compared to control treatments.In vivo pharmacokinetic analysis revealed that following intravenous administration to mice,CTX and PoP exhibited somewhat altered circulation profiles,suggesting that the CTX may have exchanged with serum factors in blood.Nevertheless,when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors,tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were ineffective.These results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.展开更多
基金supported by the National Institutes of Health of the US(DP5OD017898 and R01EB017270)the National Science Foundation of the US(1555220)+1 种基金the National Natural Science Foundation of China(32071384)the National Key Research and Development Program of China(2021YFC2102300)。
基金This study was supported by the National Institutes of Health(No.R01EB017270)The National Natural Science Foundation of China(No.82001752)。
文摘Photodynamic therapy(PDT)is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent chemotherapy.Previously,we demonstrated that liposomes containing a bilayer-anchored photosensitizer(porphyrin-phospholipid;PoP)can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with red-light.In the present work,we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of liposomes.Cabazitaxel(CTX)is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar%PoP,generating CTX-loaded PoP liposomes(CTX-PoP-Lip).CTX-PoP-Lip showed unilamellar vesicle morphology,and exhibited integrity in storage and serum,while maintaining drug stability under laser irradiation.In vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip,compared to control treatments.In vivo pharmacokinetic analysis revealed that following intravenous administration to mice,CTX and PoP exhibited somewhat altered circulation profiles,suggesting that the CTX may have exchanged with serum factors in blood.Nevertheless,when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors,tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were ineffective.These results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.
