Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive po...

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Main Authors: Ka Hong Wong (Author), Zhaopei Guo (Author), Di Jiang (Author), Xingzhi Zhou (Author), Lizhu Lin (Author), Denggao Zhao (Author), Meiwan Chen (Author)
Format: Book
Published: Elsevier, 2023-01-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Ka Hong Wong  |e author 
700 1 0 |a Zhaopei Guo  |e author 
700 1 0 |a Di Jiang  |e author 
700 1 0 |a Xingzhi Zhou  |e author 
700 1 0 |a Lizhu Lin  |e author 
700 1 0 |a Denggao Zhao  |e author 
700 1 0 |a Meiwan Chen  |e author 
245 0 0 |a Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy 
260 |b Elsevier,   |c 2023-01-01T00:00:00Z. 
500 |a 1818-0876 
500 |a 10.1016/j.ajps.2022.100773 
520 |a Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy. 
546 |a EN 
690 |a Dimeric camptothecin 
690 |a pH-sensitive 
690 |a Redox-responsive 
690 |a Cancer therapy 
690 |a Self-assembled micelle 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Asian Journal of Pharmaceutical Sciences, Vol 18, Iss 1, Pp 100773- (2023) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1818087622001222 
787 0 |n https://doaj.org/toc/1818-0876 
856 4 1 |u https://doaj.org/article/b80b3c02e2a441fc9b9f5ebf26c6981c  |z Connect to this object online.