Theranostics 2018; 8(10):2634-2645. doi:10.7150/thno.24705
Tumour-homing chimeric polypeptide-conjugated polypyrrole nanoparticles for imaging-guided synergistic photothermal and chemical therapy of cancer
1. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
2. Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer.
Methods: A tumour-homing chimeric polypeptide C-ELP-F3 was genetically engineered, and chemoselectively conjugated to polypyrrole (PPy) nanoparticles via a facile thiol-maleimide coupling reaction to form ELP-F3 conjugated PPy (PPy-ELP-F3) nanoparticles. Doxorubicin (DOX) was physically adsorbed onto PPy-ELP-F3 nanoparticles to yield DOX-loaded PPy-ELP-F3 (DOX/PPy-ELP-F3) nanoparticles. The physicochemical properties of DOX/PPy-ELP-F3 were characterized. The pharmacokinetics of DOX/PPy-ELP-F3 was studied in a mouse model. The photoacoustic imaging and photothermal imaging of tumours were tested in a melanoma-bearing mouse model. The photothermal-chemical combination therapy of tumours was investigated by using melanoma cells in vitro and in a melanoma-bearing mouse model.
Results: DOX/PPy-ELP-F3 nanoparticles showed enhanced cytotoxicity to melanoma cells in vitro and improved tumour-targeting efficiency in vivo, as compared with both DOX/PPy-ELP nanoparticles without the tumour-homing function and free DOX. The photothermal effect of DOX/PPy-ELP-F3 nanoparticles could accelerate the release of DOX from PPy-ELP-F3. Under the guidance of photoacoustic and photothermal imaging, the synergy of photothermal and chemical therapy could completely abolish tumours without detectable systemic toxicity.
Conclusion: Tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles are promising as a new multifunctional drug delivery platform for highly-efficient imaging guided combination therapy.
Keywords: tumour targeting, nanomedicine, polypyrrole, photothermal therapy, combination therapy
Sun M, Guo J, Hao H, Tong T, Wang K, Gao W. Tumour-homing chimeric polypeptide-conjugated polypyrrole nanoparticles for imaging-guided synergistic photothermal and chemical therapy of cancer. Theranostics 2018; 8(10):2634-2645. doi:10.7150/thno.24705. Available from http://www.thno.org/v08p2634.htm