Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic-Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport.
Song-Yu WuYa-Xi YeQing ZhangQian-Jin KangZhu-Min XuShen-Zhen RenFan LinYong-Tao DuanHao-Jun XuZi-Yi HuSui-Sui YangHai-Liang ZhuMei-Juan ZouZhong-Chang WangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti-tumor treatment. In addition, central nervous system neoplasm-targeted nanoplatforms are urgently required. To address these issues, a new multi-functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP-TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione-responsive disulfide bond. Mechanistically, ODP-TH crosses the blood-brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down-regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1-α (HIF-1α). The results reveal that ODP-TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP-TH achieves a more efficient tumor-inhibiting effect. This study not only overcomes the hypoxia-related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi-functional targeted and intensive anti-tumor nanoplatform.
Keyphrases
- cancer therapy
- photodynamic therapy
- drug delivery
- combination therapy
- protein protein
- fluorescence imaging
- binding protein
- dna damage
- multidrug resistant
- locally advanced
- signaling pathway
- blood brain barrier
- genome wide
- drug release
- single cell
- gene expression
- low grade
- high grade
- microbial community
- transcription factor
- red blood cell