Fabrication of Redox- Responsive Doxorubicin and Paclitaxel Prodrug Nanoparticles with Microfluidics for Selective Cancer Therapy

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Xiaodong Ma, Ezgi Özliseli, Yuezhou Zhang, Guoqing Pan, Dongqing Wang,Hongbo Zhang
Publiceringsår: 2019
Tidskrift: Biomaterials Science
Volym: 7
Nummer: 2
Artikelns första sida, sidnummer: 634
Artikelns sista sida, sidnummer: 644


Abstrakt

Cancer is a very complicate disease that needs very potent drug/drugs, which induce heavy adverse drug effects. Thus, different approaches have been applied to improve the targeted delivery of cancer drugs, for example by using nanocarriers. However, the nanocarriers are foreign stuffs, that needs further to be validated for their biocompatibility and biodegradability. In this study, we have chemically conjugated hydrophilic anticancer drug doxorubicin (DOX) with hydrophobic drug Paclitaxel (PTX) through redox-sensitive disulfide bond, abbreviated as DOX-S-S-PTX. Subsequently, due to the amphiphilic characterization, the prodrug can self-assemble into nanoparticles under microfluidic nanoprecipitation. This novel prodrug nanoparticle has super high drug loading degree of 89%, which is impossible to be achieved by any nanocarrier systems, and can be tailored to 180 nm to deliver themselves to the target, and release DOX and PTX under redox condition, which is often found in cancer cells. By evaluate the cell variability in MDAMB-231 cell, MDAMB-231-DOX cell and MEFs cell, we noticed that the prodrug nanoparticles efficiently killed the cancer cells, and conquered the MDAMB-231-DOX selective. Meanwhile, it killed much less MEFs cell due to the lacking of redox condition. The cell interaction results show that the reduced intermediate of prodrug can also bind to parent drug bilological targets. The hemolysis results shown that the nanoparticles are biocompatible in blood. Thecomputer modeling suggested that the prodrug is unlikely bind to biological targets that parent drugs still strongly interact with. At last, we confirm that the prodrug nanoparticles have no therapeutic effect in blood and health cells, but can selectively kill the cancer cells are rich of redox condition to cleave the disulfide bond and release the drugs DOX and PTX.


Senast uppdaterad 2019-07-12 vid 03:03

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