Peptide dendrimer-Doxorubicin conjugate-based nanoparticles as an enzyme-responsive drug delivery system for cancer therapy.
Peptide dendrimers have shown promise as an attractive platform for drug delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive drug delivery vehicle. The drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale drug delivery vehicle for the breast cancer therapy.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
Chengyuan
C
Zhang
Dayi
D
Pan
Kui
K
Luo
Wenchuan
W
She
Chunhua
C
Guo
Yang
Y
Yang
Zhongwei
Z
Gu
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution; D014184:Transplantation, Homologous
D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; D004798:Enzymes; C504380:Gly-Phe-Leu-Gly; D009842:Oligopeptides; D011092:Polyethylene Glycols; D004317:Doxorubicin
breast cancer therapy; drug delivery system; nanoparticles; peptide dendrimers