Docetaxel prodrug and hematoporphyrin co-assembled nanoparticles for anti-tumor combination of chemotherapy and photodynamic therapy.

Abstract

To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, in vitro anti-tumor activity, pharmacokinetic behavior in rats, in vivo distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (H2O2). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. In vivo pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.

• Authors: Guolian Ren, Yujie Li, Canqi Ping, Danyu Duan, Ning Li, Jiaqi Tang, Rongrong Wang, Wenju Guo, Xiaomin Niu, Qiuyue Ji, Guoshun Zhang, Ruili Wang, Shuqiu Zhang
• Journal: Drug delivery (Drug Deliv) Vol. 29 Issue 1 Pg. 3358-3369 (Dec 2022) ISSN: 1521-0464 [Electronic] England
• PMID: 36397301 (Publication Type: Journal Article)

Chemical References

• Hematoporphyrins
• Docetaxel
• Prodrugs
• Hydrogen Peroxide
• Drug Carriers

Topics

• Rats
• Mice
• Animals
• Hematoporphyrins (pharmacology)
• Docetaxel (pharmacology)
• Photochemotherapy
• Prodrugs (pharmacology)
• Hydrogen Peroxide
• Drug Carriers
• Nanoparticles
• Neoplasms