Docetaxel Prodrug and Hematoporphyrin Co-assembled Nanoparticles for Anti-tumor Combination of Chemotherapy and Photodynamic Therapy

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2022 Nov 18

PMID 36397301

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

Affiliations

Soon will be listed here.

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, anti-tumor activity, pharmacokinetic behavior in rats, 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 (HO). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. 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.

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