Synergistic chemo-photothermal therapy of castration-resistant prostate cancer by single-walled carbon nanotube / 上海交通大学学报（医学版）

ABSTRACT

Objective : To study the synergistic effect of chemo-photothermal on castration-resistant prostate cancer (CRPC) for enhancing the efficacy of chemotherapy by single-walled carbon nanotubes (SWCNTs). Methods ¡¤ High-purity SWCNTs were used as the drug carrier. Firstly, SWCHTs were truncated (shorten SWCNTs, s-SWCNTs) by mixed acid solutions. At the same time, a large amount of -COOH were in-troduced onto the surface of s-SWCNTs. Secondly, the polyethylene glycol (PEG) with amino terminated was successfully modified onto s-SWCNTs through amido linkage in N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride solutions to endow s-SWCNTs with water solubility and biocompatibility. Finally, docetaxel (DTX) was successfully loaded through nano-deposition method and π-π stacking on the surface of s-SWCNTs. Thus a nanosystem with both chemotherapy and photothermal properties was established. The chemo-photothermal therapy synergistic inhibition on CRPC cell line C4-2 in vitro and the anti-tumor effect in vivo were evaluated. Results ¡¤ Fourier transform infrared spectrum and zeta potential test showed that -COOH was successfully introduced onto s-SWCNTs, and the amount of -COOH was 0.412 mol per gram of SWCNTs determined by automatic conduct metric titration. The UV absorption spectrum showed that DTX was successfully loaded onto the nanosystem. By monitoring the UV absorption of the dialysate, DTX could be loaded onto SWCNTs up to 1.35 mg per gram of s-SWCNTs. Under the stimulation of acidic conditions, DTX could be rapidly released from the surface of the nanosystem. The in vitro cell viability and in vivo anti-tumor experiment showed that DTX combined with photothermal had a synergetic effect on killing C4-2 cells than any single treatment model. Conclusion ¡¤ DTX-loaded s-SWCNTs nanosystem with high stability and photothermal effect can inhib-it the growth of CRPC cells and the tumor growth in mice bearing CRPC. The nanosystem with synergistic effect of chemotherapy and photo-thermal therapy could be used in the treatment of prostate cancer which is resistant to chemotherapy drugs.