College of Pharmacy,Seoul National University,Republic of Korea

Potential of nano carriers as cancer cell-specifc drug delivery systems in photodynamic therapy

Chang-Koo Shim*,1,Ji-Eun Chang2

College of Pharmacy,Seoul National University,Republic of Korea

A R T I C L E I N F O

Article history:

Available online 23 November 2015

Photodynamic therapy

Hematoporphyrin

Doxorubicin

Nanoparticles

Liver cancer

Photodynamic therapy(PDT)in combination with chemotherapy has great potential for cancer treatment[1,2].However, there have been very few attempts to develop cancer-targeted co-delivery systems of photosensitizers and anticancer drugs. We developed hematoporphyrin(HP)-modifed doxorubicin (DOX)-loaded bovine serum albumin nanoparticles(HP-NPs)in an attempt to improve the therapeutic effect of PDT in treating liver cancer.

The HP-NPs were prepared by conjugation of amino groups on the surface of nanoparticles with HP,which is not only a ligand for low density lipoprotein(LDL)receptors on the hepatoma cells but also a well-known photosensitizer for PDT.In vitro phototoxicity in HepG2(human hepatocellular carcinoma)cells and in vivo anticancer effcacy in HepG2 tumor-bearing mice of free HP and HP-NPs were evaluated. The laser conditions were fxed at 630 nm and 400 mW, while the irradiation time and the number of PDT sessions were variable.

The in vitro phototoxicity in HepG2 cells determined by MTT assay,annexin V-FITC staining and FACS analysis was enhanced in HP-NPs compared with free HP.Furthermore, compared with free HP-based PDT,in vivo anticancer effcacy in HepG2 tumor-bearing mice was markedly improved by HPNPs-based PDT.Moreover,in both cases,the therapeutic effect was increased according to the irradiation time and the number of PDT sessions.

In conclusion,the HP-NPs prepared in this study represent a potentially effective co-delivery system of photosensitizer(HP)and anticancer drug(DOX),which improved the effects of PDT in liver cancer.

Fig.1–H&E staining of tumor tissues in HepG2 tumor-bearing mice on days 7 and 14,after double(on days 0 and 7) intravenous injection of PBS,free HP and HP-NPs with 200 J/cm2light irradiation 1 day after each injection(on days 1 and 8).

Acknowledgement

The authors are indebted to J.Patrick Barron,Professor Emeritus,Tokyo Medical University,and Adjunct Professor,Seoul National University Bundang Hospital,for his pro bono editing of this manuscript.

R E F E R E N C E S

[1]Canti G,Nicolin A,Cubeddu R,et al.Antitumor effcacy of the combination of photodynamic therapy and chemotherapy in murine tumors.Cancer Lett 1998;125(1–2):39–44.

[2]Casas A,Fukuda H,Riley P,et al.Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin.Cancer Lett 1997;121(1):105–113.

*E-mail address:shimck@daewoong.co.kr.

1Present address:Daewoong Life Science Research Institute,Yongin-Si,Gyeonggi-do,Republic of Korea.

2Present address:Department ofThoracic and Cardiovascular Surgery,Seoul National University Bundang Hospital,Seongnam-Si,Gyeonggido,Republic of Korea.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.008

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).