TY - JOUR
T1 - The impact of PEG chain length on the in vivo tumor accumulation of self-assembled amphiphilic drug-PEG polymeric micelles
AU - Zheng, Meichen
AU - Mei, Ting
AU - Deng, Caiting
AU - Xin, Jingqi
AU - Aras, Omer
AU - An, Feifei
AU - Chen, Nandi
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2024/2/5
Y1 - 2024/2/5
N2 - The integration of a drug and polyethylene glycol (PEG) into an amphiphilic polymer to form self-assembled micelles with high drug loading for self-delivery to tumors is recently reported, which has showed high clinical availability. However, the effect of PEG chain length on cell internalization efficiency and tumor targeting efficiency in this PEG-drug conjugate micelle self-delivery system has yet to be studied. Herein, pyropheophorbide-a (PhA) was used as a model drug and a fluorescent tracer to synthesize amphiphilic polymers with varying PEG chain lengths, which self-assembled into PhA-PEG2000 NPs and PhA-PEG5000 NPs with high drug loading (21.2% and 9.7%, respectively, according to calculation). The results showed that PhA-PEG2000 NPs had higher cell internalization in vitro than PhA-PEG5000 NPs, but much lower tumor accumulation in vivo than PhA-PEG5000 NPs. This was attributed to the longer in vivo blood circulation time of the latter. Furthermore, the in vitro and in vivo examinations revealed negligible side effects, indicating the intrinsic safety of the micelles. This study provides insight into the influence of PEG chain length on biodistribution of organs and tumor accumulation after intravenous administration of PEG-drug conjugate micelle and guides the design of drug incorporated amphiphilic polymer-based micelles.
AB - The integration of a drug and polyethylene glycol (PEG) into an amphiphilic polymer to form self-assembled micelles with high drug loading for self-delivery to tumors is recently reported, which has showed high clinical availability. However, the effect of PEG chain length on cell internalization efficiency and tumor targeting efficiency in this PEG-drug conjugate micelle self-delivery system has yet to be studied. Herein, pyropheophorbide-a (PhA) was used as a model drug and a fluorescent tracer to synthesize amphiphilic polymers with varying PEG chain lengths, which self-assembled into PhA-PEG2000 NPs and PhA-PEG5000 NPs with high drug loading (21.2% and 9.7%, respectively, according to calculation). The results showed that PhA-PEG2000 NPs had higher cell internalization in vitro than PhA-PEG5000 NPs, but much lower tumor accumulation in vivo than PhA-PEG5000 NPs. This was attributed to the longer in vivo blood circulation time of the latter. Furthermore, the in vitro and in vivo examinations revealed negligible side effects, indicating the intrinsic safety of the micelles. This study provides insight into the influence of PEG chain length on biodistribution of organs and tumor accumulation after intravenous administration of PEG-drug conjugate micelle and guides the design of drug incorporated amphiphilic polymer-based micelles.
KW - Fluorescence imaging
KW - PEG chain length
KW - Polyethylene glycol
KW - Tumor accumulation
UR - https://www.scopus.com/pages/publications/85178123415
U2 - 10.1016/j.colsurfa.2023.132823
DO - 10.1016/j.colsurfa.2023.132823
M3 - 文章
AN - SCOPUS:85178123415
SN - 0927-7757
VL - 682
JO - Colloids and Surfaces A: Physicochemical and Engineering Aspects
JF - Colloids and Surfaces A: Physicochemical and Engineering Aspects
M1 - 132823
ER -