ab0c00163_si_001.pdf (1.38 MB)
Tumor-Targeting Polycaprolactone Nanoparticles with Codelivery of Paclitaxel and IR780 for Combinational Therapy of Drug-Resistant Ovarian Cancer
journal contribution
posted on 2020-03-23, 12:33 authored by Qianqian Pan, Jingjun Tian, Huihui Zhu, Liangjie Hong, Zhengwei Mao, Joaquim Miguel Oliveira, Rui L. Reis, Xiao LiSynergetic treatments
that combine chemotherapy with photothermal/photodynamic
therapy have been developed as promising new strategies for cancer
therapy, especially for drug-resistant cancers. To achieve optimized
synergetic outcomes for cancer therapy, it is highly desirable to
selectively and simultaneously deliver both chemotherapeutics and
near-infrared photosensitizers to the cancer tissues and cells, enhancing
local accumulation. Here we report the preparation of poly-ε-caprolactone
nanoparticles (PCL NPs) using bovine albumin as a stabilizer; the
nanoparticles are loaded with IR780 and paclitaxel (PTX) for combinational
phototherapy and chemotherapy. Moreover, in order to enable active
targeting toward ovarian cancer, a specific peptide recognizing luteinizing
hormone-releasing hormone receptors (LHRH) on ovarian cancer cells
was covalently grafted onto the surface of the as-prepared NPs. As
a result, LHRH peptide modified PCL (PCL-LHRH) NPs demonstrated increased
internalization in ovarian tumor cells in vitro and selective targeting
in tumor xenografts in vivo. PTX and IR780 can be efficiently encapsulated
into PCL-LHRH NPs by an oil-in-water emulsion and solvent evaporation
method. The systematic administration of ovarian tumor targeting PCL-LHRH/IR780-PTX
can efficiently hinder the growth of drug-resistant xenografts in
vivo with the assistance of an 808 nm near-infrared laser. These findings
indicate that peptide mediated tumor targeting multifunctional nanomaterials
may have remarkable profits in controlled drug delivery and synergistic
therapy on drug-resistant cancer.