Bioresponsive albumin-conjugated paclitaxel prodrugs for cancer therapy

Abstract

The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.

A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy

“…The prolonged circulation in the blood could promote the accumulation of the nanoparticles in tumor tissues through the EPR effect (Yang et al., 2018 ). The long half-life of both polymeric micellar preparations contributed to promoting drug accumulation in tumor tissue, and as confirmation, biodistribution assays of all UA formulations were performed using MG-63 tumor-bearing mice.…”

“…PEG-SS-UA can self-assemble to form a micelle (U-SS-M) in an aqueous solution ( Scheme 1 ). U-SS-M can significantly increase the water solubility of UA, exhibit an excellent prolonged blood circulation time, and can selectively accumulate in tumor tissue via enhanced permeability and retention (EPR) effect (Yang et al., 2018 ; Goos et al., 2020 ) mediated-passive-targeting, and thus, sufficiently and selectively release the drug in tumor cells. U-SS-M can effectively suppress aggressive human OS MG-63 tumor growth in vitro and in vivo .…”

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

“…Chemotherapy is still the most effective and efficient way to treat cancer in clinic even with the rapid development of nanotechnology recently (Galluzzi et al, 2015;Hallaj-Nezhadi & Hassan, 2015;Gandhi et al, 2018;Srinivasan et al, 2018). A series of chemical anticancer drugs have been well developed and clinically used in these decades, such as doxorubicin (DOX) (Zhang et al, 2012;Fabbri et al, 2016), paclitaxel (PTX) (Markman & Mekhail, 2002;Yang et al, 2018), and camptothecin (CPT) (Venditto & Simanek, 2010;Llin as et al, 2018); however, these drugs are limited in the further clinical applications due to the serious side-effects caused by offtargeting and low therapeutic efficacy (Jungk et al, 2016;Yoshizawa et al, 2016). To overcome these obstacles, nanoscale drug delivery systems (DDSs) have attracted more and more attention and been extensively investigated (Chen et al, 2014), such as polymeric micelles (PMs), nanoparticles (NPs), prodrug, and liposome (Zhang et al, 2016;Zylberberg & Matosevic, 2016;Huang et al, 2018;Li et al, 2018;Dong et al, 2019).…”

Tumor microenvironment responsive drug delivery systems

“…This is also accompanied with polar transition of the polymer from hydrophilic to hydrophobic, resulting in shell dissociation and further exposure of the positive charged CDs-Pt (IV). In addition to PEG corona, He's group reported a novel strategy to avoid nonspecific absorption from plasma proteins [30] , [31] , [32] . In their works, the model drug was linked with maleimide via tumor responsive moieties to form the prodrug.…”