An Albumin-Based Therapeutic Nanosystem for Photosensitizer/Protein Co-Delivery to Realize Synergistic Cancer Therapy.
Shu-Lun AiCai-Xia WangYan PengYi TuJin-Ju LeiChang XuXiao-He RenSi-Xue ChengPublished in: ACS applied bio materials (2021)
Oxygen-dependent photodynamic therapy (PDT) is hindered by the limited availability of endogenous oxygen in solid tumors and low tumor accumulation of photosensitizers. Herein, we developed a biocompatible cancer-targeted therapeutic nanosystem based on cRGD conjugated bovine serum albumin (CBSA) co-loaded with a photosensitizer (chlorin e6, Ce6) and a therapeutic protein (cytochrome c, Cytc) for synergistic photodynamic and protein therapy. The nanosystem (Ce6/Cytc@CBSA) can target α V β 3 integrin overexpressed cancer cells to improve tumor accumulation due to incorporation of cRGD. In the intracellular environment, Ce6 is released to produce toxic singlet oxygen upon near-infrared irradiation. At the same time, the therapeutic protein, Cytc, can induce programmed cell death by activating the downstream caspase pathway. Most importantly, Cytc with the catalase-like activity accelerates O 2 generation by decomposing excess H 2 O 2 in cancer cells, thereby relieving the PDT-induced hypoxia to enhance therapeutic efficacy. Both in vitro and in vivo studies reveal the significantly improved antitumor effects of the combined photodynamic/protein therapy, indicating that Ce6/Cytc@CBSA shows great potential in synergetic cancer treatments.
Keyphrases
- photodynamic therapy
- cancer therapy
- fluorescence imaging
- drug delivery
- protein protein
- amino acid
- papillary thyroid
- stem cells
- squamous cell carcinoma
- young adults
- endothelial cells
- cell death
- gene expression
- climate change
- squamous cell
- single cell
- dna methylation
- genome wide
- bone marrow
- human health
- diabetic rats
- stress induced
- smoking cessation