Multistage pH‐Responsive Liposomes for Mitochondrial‐Targeted Anticancer Drug Delivery

Abstract

Zwitterionic oligopeptide liposomes (HHG2C(18)-L) containing a smart lipid (1,5-dioctadecyl-L-glutamyl 2-histidyl-hexahydrobenzoic acid, HHG2C(18)) are developed to overcome the barriers faced by anticancer drugs on the route from the site of injection into the body to the final antitumor target within transport steps with multiple physiological and biological barriers. HHG2C(18)-L show the multistage pH-responsive to the tumor cell (the mitochondria in this case). Their multistage pH response leads to more effective entry of the tumor cell, improved escape from the endolysosomes, and accumulation at the mitochondria (see picture).

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

“…Acid-labile zwitterionic peptide lipid derivatives are another class of pH-responsive lipids that have been employed to devising fusogenic liposomes that facilitates uptake as well as drug release (79)…”

ATP-triggered anticancer drug delivery

“…8), followed by internalization via the clathrin-mediated pathway ( Supplementary Fig. 9) and subsequent transportation into the endosomes and lysosomes 43,44 . As shown in Fig.…”

A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery

“…In brief, 500 mL of P-GFLG-FITC or P-GG-FITC conjugates containing FITC-labeled subunits (equivalent FITC concentration: 600 mg/mL) were transferred into the dialysis membrane (MWCO 5000) and dialyzed against 8 mL of 0.1 M citrate/phosphate buffer (pH 6.0) containing 2 Â 10 À3 M EDTA with or without 2 mM papain at 37 C. At 0.1, 0.5, 1, 2, 3, 4, 6,7,8,9,19,21,24, and 48 h, 100 mL of the external buffer was collected and replaced by the fresh buffer. The concentration of FITC (excitation at 485 nm and emission at 518 nm) was determined with a Varioskan Flash.…”