Overcoming the polyethylene glycol dilemma via pathological environment-sensitive change of the surface property of nanoparticles for cellular entry

Journal of Controlled Release : Official Journal of the Controlled Release Society
Susumu HamaK Kogure

Abstract

Modification with polyethylene glycol (PEG) is currently considered an important strategy for anti-cancer drug delivery, because PEGylated-nanoparticles would be effectively delivered to tumor tissue by enhanced permeation and retention effects. However, PEGylation suppresses the cellular uptake of nanoparticles (NPs) to target cells (known as the PEG dilemma). Here, we propose a novel strategy, namely conferring a pathological environment-sensitive property of nanoparticles for overcoming the PEG dilemma. Specifically, although nanoparticles have an overall negative surface charge to avoid interactions with biogenic substances in blood circulation, inversion of surface charge (to positive) at the pH of the tumor microenvironment may allow the nanoparticles to be taken up by cancer cells. To prove this concept, charge-invertible nanoparticles modified with novel slightly acidic pH-sensitive peptide (SAPSP-NPs) were developed. The negatively-charged SAPSP-NPs were delivered to tumor tissue, and were successfully taken up by cancer cells upon inversion of the surface charge to positive at intratumoral pH. SAPSP-NPs may serve as an alternative carrier to the PEGylated NP for anti-cancer drug delivery.

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Citations

Jan 27, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Qiang Peng, Huiling Mu
Oct 7, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rahel ZulligerMuna I Naash
May 18, 2016·Advanced Drug Delivery Reviews·Hanna J WagnerWilfried Weber
Sep 7, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Anna LechanteurGéraldine Piel
Apr 6, 2017·Nanomaterials·Katyayani TatipartiArun K Iyer
Feb 16, 2019·Current Medicinal Chemistry·Xinyu HeZiyang Cao
Feb 25, 2017·Advanced Materials·Qihang SunYouqing Shen
Feb 18, 2021·ACS Applied Materials & Interfaces·Miguel Gisbert-GarzaránMaría Vallet-Regí
Jun 30, 2016·Advanced Drug Delivery Reviews·Hyun Jin KimKazunori Kataoka
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gennara CavallaroGaetano Giammona
Jun 22, 2021·International Journal for Numerical Methods in Biomedical Engineering·Abhignyan NagesettiAnthony J McGoron
Jul 20, 2018·ACS Omega·Joan EstelrichMaría Del Carmen Morán
Jan 30, 2019·ACS Applied Materials & Interfaces·Barbara PoinardJames Chen Yong Kah
Apr 11, 2019·Molecular Pharmaceutics·Xinlong ZangDawei Chen
May 13, 2019·ACS Biomaterials Science & Engineering·Dimitrina BabikovaIvaylo Dimitrov
Jul 7, 2021·Nature Materials·Irene de Lázaro, David J Mooney

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