Chlorin e6-Encapsulated Polyphosphoester Based Nanocarriers with Viscous Flow Core for Effective Treatment of Pancreatic Cancer.
Lack of effective treatment results in the low survival for patients with pancreatic cancer, and photodynamic therapy (PDT) with photosensitizers has emerged as an effective therapeutic option for treatment of various tumors by light-generated cytotoxic reactive oxygen species (ROS) to induce cell apoptosis or necrosis. However, the poor solubility, rapid blood clearance, and weak internalization of the photosensitizer seriously inhibit its anticancer efficacy. To overcome these obstacles, a polyphosphoester-based nanocarrier (NP-PPE) is employed as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6), for photodynamic therapy. The Ce6-encapsulated nanocarrier (NP-PPE/Ce6) significantly promoted the cellular internalization of Ce6, enhanced the generation of ROS in the tumor cells after irradiation. Therefore, the cellular phototoxicity of NP-PPE/Ce6 against BxPC-3 pancreatic cancer cells was markedly enhanced than that of free Ce6 in vitro. Furthermore, NP-PPE/Ce6 improved accumulation of Ce6 in tumor tissue and treatment with NP-PPE/Ce6 significantly enhanced antitumor efficacy in human BxPC-3 pancreatic cancer xenografts. These results suggest that using a polyphosphoester-based nanocarrier as the delivery system for a photosensitizer has great potential for PDT of pancreatic cancer.
Division of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University , No.17 Lu Jiang Road, Hefei, Anhui 230001, China.
Fei
F
Ding
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui 230027, P.R. China.
Hong-Jun
HJ
Li
Department of Medical Materials and Rehabilitation Engineering, School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, China.
Jun-Xia
JX
Wang
Department of Medical Materials and Rehabilitation Engineering, School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, China.
Wei
W
Tao
Department of Medical Materials and Rehabilitation Engineering, School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, China.
Yan-Hua
YH
Zhu
Division of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University , No.17 Lu Jiang Road, Hefei, Anhui 230001, China.
Yue
Y
Yu
Department of Medical Materials and Rehabilitation Engineering, School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, China.
Xian-Zhu
XZ
Yang
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D002735:Chlorophyllides; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C062985:phytochlorin
drug delivery; nanomedicine; pancreatic cancer; photodynamic therapy; polyphosphoester