Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents

Abstract

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile β-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.

Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer

“…PZL copolymers with a PEI core and poly(ε-benzyloxycarbonyl-L-lysine) side chains were synthesized using ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydride (NCA), as described in our previous study [ 24 , 25 ]. Briefly, ε-benzyloxycarbonyl-L-lysine N-carboxyanhydride (Lys(Z)-NCA) was prepared via the Fuchs–Farthing method using ε-benzyloxycarbonyl-L-lysine and triphosgene in anhydrous ethyl acetate [ 26 ]. Subsequently, Lys(Z)-NCA was dissolved in an anhydrous mixture of DMSO and DCM (1:5 volume ratio).…”

Switching it Up: The Promise of Stimuli‐Responsive Polymer Systems in Biomedical Science

“…Poly(L-ornithine)-block-poly(L-phenylalanine) (PLO-block-PLF) copolypeptides self-assembling as nanosized micelles, which can interact with cancer cells through electrostatic interactions and kill them via membrane lysis, were synthesized in work. [108] By adding 1,2-dicarboxylic-cyclohexene anhydride (DCA) to the PLO side chains, PLO(DCA)-block-PLF was fabricated (Figure 9e), which showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recov-Figure 9. pH-sensitive LbL thin films containing insulin and insulin release (a).…”

“…These pH-responsive systems and their pharmaceutical applications were intensively studied by the Khutorianskiy group. [107][108][109] In particular, in these studies poly(acrylic acid), poly(methacrylic acid), or a polymer with hydroxyl groups were used to prepare interpolymer or intrapolymer complexes for the encapsulation of drugs. These polymers can be complexed with various classes of water-soluble non-ionic polymers: [109][110][111] 1. polymers containing lactam groups such as poly(vinyl pyrrolidone), poly(vinyl caprolactam); 2. polymers containing ether groups in the backbone, such as poly(ethylene oxide), poly(propylene oxide), or as pendants, such as poly(vinyl methyl ether); 3. acrylic type polymers, such as polyacrylamide, poly(Nisopropylacrylamide), poly(N,N-dimethyl acrylamide); 4. polymeric alcohols such as poly(vinyl alcohol), poly(2hydroxyethylacrylate), poly(vinyl ether of ethyleneglycol) and poly(vinyl ether of diethyleneglycol); 5. other synthetic polymers such as poly(ethyloxazoline) and poly(N-acetyliminoethylene); 6. polysaccharides such as water-soluble non-ionic cellulose ethers (e. g., hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose).…”

Copolymer Micelles: A Focus on Recent Advances for Stimulus-Responsive Delivery of Proteins and Peptides

“…This system showed excellent antimicrobial activity on biofilm-infected diabetic mice. Interestingly, a similar approach of negative-to-positive charge reversal induced in mildly acidic conditions (with maleic anhydride derivative) was used to recover the cationic character of antimicrobial poly(L-ornithine) at the micelle surface and thus cytotoxic efficiency selectively on tumor cells [63].…”