Abstract
The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.
Highlights
The emergence of photothermal therapy (PTT) and photodynamic therapy (PDT) has gotten a satisfactory therapeutic effects, and so researchers have attempted to combine PTT and PDT to change therapeutic strategies and improve treatment effects in cancer therapy [1,2,3,4]
3.42 ppm, 4.08 ppm, and 4.14 ppm were attributed to the protons from biodegradable photoluminescent polymers (BPLPs) segments
These results revealed that doxorubicin/cypate-loading biodegradable micelles (DCBMs) decomposition of cypate accompanied the generation of cypate accompanied the generation of O2 [27]
Summary
The emergence of photothermal therapy (PTT) and photodynamic therapy (PDT) has gotten a satisfactory therapeutic effects, and so researchers have attempted to combine PTT and PDT to change therapeutic strategies and improve treatment effects in cancer therapy [1,2,3,4]. PDT therapy is based on the generation of reactive oxygen species to kill cancer cells when photosensitizers are exposed to various wavelengths of light in the presence of dissolved oxygen [6]. These synergic therapy methods have achieved efficient antitumor activity through the phototoxicity of PTT or PDT.
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