Developing biocompatible and photodegradable photothermal agents (PTAs) holds great promise for potential clinical applications in photothermal cancer therapy. Herein, a new PTA was innovatively constructed by conjugating the hydrophobic near-infrared (NIR) heptamethine cyanine molecule IR825-NH2 with a double hydrophilic block copolymer methoxypoly(ethylene glycol)5k-block-poly(L-aspartic acid sodium salt)10 (abbreviated as PEG-PLD) via amine-carboxyl reaction. The as-designed PEG-PLD(IR825) was amphiphilic and could self-assemble into polymeric nanomicelles in aqueous solutions. Benefiting from the chemical conjugation strategy, PEG-PLD(IR825) nanomicelles realized a considerably high drug loading rate (∼21.0%) and substantially avoided the premature release of IR825 during systemic circulation. Confocal imaging revealed that the nanomicelles mainly located at mitochondria and endoplasmic reticulum after cellular internalization. In vitro photothermal therapy demonstrated the excellent cancer killing efficiency of PEG-PLD(IR825) nanomicelles due to their high light-to-heat conversion efficiency upon NIR laser irradiation. In addition, PEG-PLD(IR825) nanomicelles showed polarity-sensitive fluorescence at ∼610 nm (under 552 nm excitation) and 830 nm (under 780 nm excitation), which was especially useful for both in vitro visible fluorescence imaging and in vivo near-infrared fluorescence imaging-guided photothermal therapy (PTT). At the in vivo level, PEG-PLD(IR825) nanomicelles exhibited an excellent tumor-homing ability and a long retention time in tumor tissues as evidenced by the in vivo fluorescence imaging results. The desirable properties of PEG-PLD(IR825) nanomicelles ensured their effective tumor ablation during PTT treatment. More importantly, the PEG-PLD(IR825) nanomicelles underwent degradation after laser irradiation, which ensured their post-treatment biosafety. Therefore, the nanomicelles are promising to serve as an efficient and safe PTA for imaging-guided photothermal cancer therapy.
Xiaowei Wang,Yanhong Liu,Yue Hu,Hong Gao,Meiling Ge,Jie Ding,Dongkai Wang
The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo . The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol) 5000 (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death . indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.
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