The synthesis of peptide‐conjugated poly(2‐ethyl‐2‐oxazoline)‐b‐poly(L‐lactide) (PEtOx‐b‐PLA) polymeric systems through the combination of controlled polymerization techniques and click reactions

Abstract

To optimize the therapeutic effect of pharmaceutical agents, drug delivery systems tailored from FDA‐approved polymers like poly(L‐lactide) (PLA) is an effective strategy. Because of their hydrophobic character, these systems greatly suffer from reduced circulation time thus, amphiphilic block copolymers became favorable to overcome this limitation. Of them, poly(oxazoline)‐b‐poly(L‐lactide) are of choice as poly(oxazoline) (PEtOx) is compatible, biodegradable, while exhibiting minimum cytotoxicity. To tailor selective drug targeting drug delivery systems, whereby their selectivity for tumor tissues is maximized, these polymers should be decorated with so‐called tumor‐homing agents, such as antibodies, peptides and so forth. To this respect, we designed a new block copolymer, allyl‐poly(2‐ethyl‐2‐oxazoline)‐b‐poly(L‐lactide) allyl‐(PEtOx‐b‐PLA) and its subsequent conjugation to tumor‐homing peptides, peptide‐18, and peptide‐563 at the terminal position. In this manuscript, we report our synthetic route to obtain this building block and its conjugation to tumor‐homing agents.

pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug

“…28,30 As promising as they appear, the development of these polymerbased nanocarriers did not obviate all the problems, including insufficient intracellular delivery and uncontrolled release of drugs within tumors. 31 Therefore, extensive research efforts have been dedicated to the development of stimuli-responsive polymeric micelles. These micelles are designed to release their payload in response to specific intracellular stimuli, including pH, reactive oxygen species (ROS), reduction, and enzymes.…”

“…Among the various options available, poly­(oxazoline) has gained significant attention as a potential substitute for PEG in biomedical applications. This is primarily due to its tunable functionality, ease of synthesis, stability, and stealth properties. , As promising as they appear, the development of these polymer-based nanocarriers did not obviate all the problems, including insufficient intracellular delivery and uncontrolled release of drugs within tumors . Therefore, extensive research efforts have been dedicated to the development of stimuli-responsive polymeric micelles.…”