Tumor-Targeting Polycaprolactone Nanoparticles with Codelivery of Paclitaxel and IR780 for Combinational Therapy of Drug-Resistant Ovarian Cancer
- Qianqian PanQianqian PanWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P. R. ChinaZhejiang Financial College, No. 118 Xueyuan Street, Hangzhou, Zhejiang 310018, P. R. ChinaMore by Qianqian Pan,
- Jingjun TianJingjun TianWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P. R. ChinaMore by Jingjun Tian,
- Huihui ZhuHuihui ZhuWomen’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P. R. ChinaMore by Huihui Zhu,
- Liangjie HongLiangjie HongMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. ChinaMore by Liangjie Hong,
- Zhengwei Mao*Zhengwei Mao*E-mail: [email protected] (Z.M.).MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. ChinaMore by Zhengwei Mao,
- Joaquim Miguel OliveiraJoaquim Miguel Oliveira3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables, and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco GMR, PortugalICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga/Guimarães, PortugalThe Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, PortugalMore by Joaquim Miguel Oliveira,
- Rui L. ReisRui L. Reis3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables, and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco GMR, PortugalICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga/Guimarães, PortugalThe Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, PortugalMore by Rui L. Reis, and
- Xiao Li*Xiao Li*E-mail: [email protected] (X.L.).Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P. R. ChinaMore by Xiao Li
Abstract
Synergetic 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.
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