Abstract
Polymeric micelles have great potential in drug delivery systems because of their multifunctional adjustability, excellent stability, and biocompatibility. To further increase the drug loading efficiency and controlled release ability, a pH-responsive hyperbranched copolymer methoxy poly(ethylene glycol)-b-polyethyleneimine-poly(Nε-Cbz-l-lysine) (MPEG-PEI-PBLL) was synthesized successfully. MPEG-PEI-NH2 was synthesized to initiate the ring-opening polymerization of benzyloxycarbonyl substituted lysine N-carboxyanhydride (Z-lys NCA). The introduction of Schiff bases in the polymer make it possible to respond to the variation of pH values, which cleaved at pH 5.0 while stable at pH 7.4. As the polymer was amphiphilic, MPEG-PEI-PBLL could self-assemble into micelles. Owing to the introduction of PEI, which make the copolymer hyperbranched, the pH-responsive micelles could efficiently encapsulate theranostic agents, such as doxorubicin (DOX) for chemotherapy and NIRF dye DiD for in vivo near-infrared (NIR) imaging. The drug delivery system prolonged the drug circulation time in blood and allowed the drug accumulate effectively at the tumor site. Following the guidance, the DOX was applied in chemotherapy to achieve cancer therapeutic efficiency. All the results demonstrate that the polymer micelles have great potential for cancer theranostics.
Highlights
Signi cant advancements have been made in cancer therapy
In order to aggregate at tumor site, particle size of the micelles should meet the condition of Enhanced Permeability and Retention (EPR) effect,[53] which was important for drug aggregating at the tumor site with no need of targeting modi cation
PH-responsive polymer micelles were successfully prepared based on triblock copolymer MPEG-PEI-PBLL
Summary
Signi cant advancements have been made in cancer therapy. Polymeric micelles are considered as one of the most effective means with a promising prospect to effectively improve the pesticide effect and reduce the side effect to the normal cells.[1,2,3,4,5,6,7] Despite the bright prospects they have, there are still some challenges need to be overcome, such as controllable drug release behavior, degradable in the body and good biocompatibility, and high drug loading capacity.[8,9,10,11,12] Without these characteristics, it is difficult to achieve the ideal therapeutic effect and even possible to cause some side effects in cancer therapy.[13,14,15]. Researchers endow the polymeric micelles pH responsiveness via introducing acid-sensitive covalent bonds.[23,24,25,26,27,28,29] Among them, Schiff base is o en used as pH-responsive linker in polymer chains. A pH-responsive copolymer based on Schiff base consisting of PEG, polyethyleneimine (PEI) and polypeptide chains was synthesized and studied as polymeric micelles. PEG was widely used as a gold standard in drug delivery system recent research revealed that it may lead to immunoreaction.[45] On one hand, hyperbranched polyethyleneimine (PEI) was introduced in the polymer to connect with PEG through Schiff base linkages to initiate ring opening reaction of lysine NCA. It is anticipated that this pHresponsive drug delivery system can greatly enhance the drug delivery efficiency and therapeutic outcome
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