The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines

Abstract

Fundamental studies on the cellular uptake and drug release of PEGylated nanomedicines are beneficial to understand their fate in vivo and construct ideal nanoparticle formulations. In this work, the detailed metabolic process of PEGylated doxorubicin (Dox) nanomedicines were investigated via confocal laser scanning microscopy (CLSM), flow cytometry (FCM), cytotoxicity test, fluorescence imaging in vivo (FLIV) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Among them, only LC-MS/MS could accurately determine the content of PEGylated Dox and Dox in vitro and in vivo. To the best of our knowledge, this was the first time the PEGylated Dox and released Dox were simultaneously quantified. The interplay of molecular structures, cellular uptake, drug release, and antitumor effect was well characterized. PEG with high molecular weight impeded the cellular uptake of nanoparticles, and the acid-labile hydrazone bond between Dox and PEG promoted Dox release significantly. Cellular uptake and drug release play decisive roles in cytotoxicity and antitumor effect, as evidenced by LC-MS/MS. We emphasized that LC-MS/MS would be a practicable method to quantify PEGylated drugs without complex tags, which could be more in-depth to understand the interaction between PEGylated nanomedicines and their antitumor efficacy.

Green Light‐Triggered Intraocular Drug Release for Intravenous Chemotherapy of Retinoblastoma

“…Meanwhile, DSPE‐mPEG (10%, w/w to DTAEA) was co‐assembled with DTAEA for surface PEGylation, which can increase the water stability of the nanoparticles, reduce immune clearance, and prolong the circulation time after systemic administration. [ 27 , 28 , 29 ] Dynamic light scattering (DLS) results showed the hydrodynamic size of 89.46 nm with a polydispersity index (PDI) of 0.14 ( Figure 2 A ). The prepared DSPE‐mPEG 2000 /DTAEA nanoparticles (abbreviated as DTNPs) were observed by transmission electron microscopy and identified as well‐dispersed spherical nanoparticles with the size of approximate 100 nm (Figure 2B ), which was consistent with the DLS result.…”

Tailoring nanoparticles based on boron dipyrromethene for cancer imaging and therapy

“…Using BODIPY as the core and hydrophilic groups as the shell, BDP NPs can be stable in aqueous solution. The hydrophilic molecules that can be bonded with BODIPY, include polyethylene glycol (Kolate et al, ; W. Li, Zhan, De Clercq, Lou, & Liu, ; Lin et al, ; Yu Zhu et al, ), zwitterions (Debayle et al, ; Ji et al, ; Sinclair et al, ; Su et al, ), peptides (T. Li, Li, et al, ; Y. Sun, Liang, et al, ), dextran (Heo et al, ; W. S. Kim et al, ; Lv et al, ; Siewert et al, ), and so on.…”

“…The hydrophilic molecules that can be bonded with BODIPY, include polyethylene glycol (Kolate et al, 2014;W. Li, Zhan, De Clercq, Lou, & Liu, 2013;Lin et al, 2018;Yu Zhu et al, 2017), zwitterions (Debayle et al, 2019;Ji et al, 2019;Sinclair et al, 2018;Su et al, 2018), peptides (T. Y. Sun, Liang, et al, 2019), dextran (Heo et al, 2017; W. S. Kim et al, 2019;Lv et al, 2018;Siewert et al, 2019), and so on.…”

Light‐triggered dePEGylation with decreasing the diameter of hydroxyapatite nanocarriers for enhanced cellular uptake and tumor penetration

“…PEG as a linear polymer, showing negative potential, has been extensively used to modify nanocarriers to improve the biocompatibility, solubility and prolong drug circulation. [ 13–21 ] PEG ligands conjugated to the surface of nanoparticles can effectively reduce the nonspecific protein adsorption and cellular uptake of the reticuloendothelial system (RES) to improve the biodistribution and prolong the blood circulation half‐life of the DDSs by the enhanced permeability and retention (EPR) effect. [ 16,18,22,23 ] However, due to the increase in the size of the nanoparticles, PEGylation of the NDDs disturbs the cellular uptake and tumor penetration.…”