Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo.
Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(ε-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG-PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Xiao-Jiao
XJ
Du
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Ji-Long
JL
Wang
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Wei-Wei
WW
Liu
Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
Jin-Xian
JX
Yang
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Chun-Yang
CY
Sun
Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
Rong
R
Sun
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Hong-Jun
HJ
Li
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Song
S
Shen
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Ying-Li
YL
Luo
Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: xdye@ustc.edu.cn.
Xiao-Dong
XD
Ye
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Yan-Hua
YH
Zhu
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Xian-Zhu
XZ
Yang
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: jwang699@ustc.edu.cn.
Jun
J
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007783:Lactones; D011091:Polyesters; D043823:Taxoids; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D000077143:Docetaxel; C016240:polycaprolactone; D011092:Polyethylene Glycols
Biological behaviors; Cancer therapy; Drug delivery; PEGylation; Polymeric nanoparticles; Self-assembly