Porphine functionalized nanoparticles of star-shaped poly(ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 1000 succinate biodegradable copolymer for chemophotodynamic therapy on cervical cancer.
We developed a system of biodegradable nanoparticles (NPs) of 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphine (TAPP) centered, 4 arm star-shaped copolymers based on poly(ε-caprolactone) (PCL) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for combinatory chemophotodynamic therapy by using docetaxel (DTX) as a model anticancer drug and TAPP as photodynamic sensitizer. TPGS component in the copolymer plays an important role in enhancing the drug encapsulation efficiency, drug release kinetics and cellular uptake of the NPs, as well as in overcoming the multidrug resistance due to inhibition of P-glycoproteins (P-gp) of the cancer cells. We demonstrated in vitro by using the MCF7/ADR breast cancer cells of P-gp overexpression and the HeLa cervical cancer cells that the proposed chemophotodynamic therapy by the DTX-loaded TAPP-PCL-b-TPGS NPs could have much higher therapeutic effect than the original drug Taxotere®. IC50 data showed that the DTX-loaded TAPP-PCL-b-TPGS NPs chemophotodynamic therapy could be 9.36 and 56.5-fold efficient after 24 and 48h treatment, respectively in comparison with the Taxotere® chemotherapy. The in vivo investigation by employing a cervical cancer xenograft model further confirmed the advantages of the proposed chemophotodynamic therapy by the DTX-loaded TAPP-PCL-b-TPGS NPs versus the Taxotere® chemotherapy.
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Wei
W
Cao
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Xiaowei
X
Zeng
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Gan
G
Liu
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
Zhen
Z
Li
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Guangdong Key Laboratory for Research & Development of Natural Drugs, Guangdong Medical College, Zhanjiang 524023, PR China.
Xiaobin
X
Zeng
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Lijun
L
Wang
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Laiqiang
L
Huang
Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore; International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, PR China.
Si-Shen
SS
Feng
The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Life Sciences, Tsinghua University, Beijing 100084, PR China. Electronic address: mei.lin@sz.tsinghua.edu.cn.
Lin
L
Mei
D020341:Absorbable Implants; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D003131:Combined Modality Therapy / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D000077143:Docetaxel; D005260:Female; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011091:Polyesters; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; C016240:polycaprolactone; D011092:Polyethylene Glycols; C107018:porphine; C014225:tocophersolan
Cancer nanotechnology; Multidrug resistance; Multimodality treatment; Photodynamic Therapy; Star-shaped copolymer