Preparation, characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS, phospholipase D inhibitor and doxorubicinPreparation, characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS, phospholipase

In the present study, we aimed to co-load the α-TOS conjugate Tat-TOS with the phospholipase D inhibitor FIPI and the antitumor drug doxorubicin（DOX） in a liposome delivery system for antitumor metastasis. Firstly, Tat-TOS was synthesized by solid-phase synthesis, and its structure was confirmed. The ability of free and liposomal Tat-TOS to induce apoptosis in vitro was evaluated by flow cytometry. Biodistribution of Tat-TOS-loaded liposomes was investigated by a molecular imaging system. Multi-component-loaded liposomes modified with Tat-TOS containing FIPI and DOX was prepared by thin film dispersion method in combination with p H gradient method and post-insertion method. Physicochemical properties were determined, and the in vitro uptake ability of the formulations was evaluated. The results showed that the prepared liposomes were characterized by a uniform particle size distribution and small particle size. The encapsulation efficiency of FIPI and DOX exceeded 85%. Both free and liposomal Tat-TOS significantly improved the activity of inducing apoptosis of tumor cells. The liposomes modified with Tat-TOS were apparently accumulated in normal lung tissue and tumor metastasized lung. Multi-component-loaded liposomes exhibited the strongest cell uptake capacity, suggesting a stronger anti-metastatic effect and anti-tumor activity in vivo.

Mitochondria-targeting polydopamine-coated nanodrugs for effective photothermal-and chemo-synergistic therapies against lung cancer

Targetingmitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance.Here,a mitochondria-targeting nanoparticle(TOS-PDA-PEG-TPP)was designed to precisely deliver polydopamine(PDA)as the photothermal agent and alphatocopherol succinate(α-TOS)as the chemotherapeutic drug to the mitochondria of the tumor cells,which inhibits the tumor growth through chemo-and photothermal-synergistic therapies.TOSPDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled byα-TOS,followed by grafting PEGand triphenylphosphonium(TPP)on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells.In vitro studies showed that TOS-PDA-PEGTPP could be efficiently internalized by tumor cells and accumulated atmitochondria,resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation.In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects.Conclusively,the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.