Side-Chain Amino-Acid-Based pH-Responsive Self-Assembled Block Copolymers for Drug Delivery and Gene Transfer

Abstract

Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

α-TOS-based RAFT block copolymers and their NPs for the treatment of cancer

“…Additionally, the SEC curves were bimodal indicating the presence of a minor fraction of unreacted PEG macro-CTA. This behavior is commonly observed for this type of polymerizations, indicating that the efficiency of macro CTA agents was not complete 53, 54 . Finally, it is noteworthy that no high MW species were observed at low retention times, confirming the absence of chain coupling reactions and the appropriate control over the RAFT polymerization.…”

Carbohydrate-Conjugated Amino Acid-Based Fluorescent Block Copolymers: Their Self-Assembly, pH Responsiveness, and/or Lectin Recognition

“…To validate the pH induced stimuli responsiveness, we analysed the turbidity of aqueous solution of 6 (0.1 wt%) at 500 nm by UV-visible spectroscopy as a function of pH, exhibiting hydrophilic to hydrophobic phase transition at pH 6.9 ( Figure 5A). 13 The effect of pH on micellar solution of amphiphilic copolymer 8 carrying multivalent -NH 2 groups on the surface was 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Figure S7 for detailed studies in the Supporting Information). Moreover, as we have shown above the propensity of micellar nanoparticle formation by copolymer 10 in aqueous solution with dual amino and sugar entities projection on the outer surface, their pH-responsive phase transition was investigated by DLS.…”

“…[9][10][11] In particular, naturally occurring amino acids, which are the constitutional component of proteins/peptides, based biohybrid materials create an important class of polymer therapeutics. [12][13][14] Thus, incorporation of both amino acids and carbohydrate biomolecules to the synthetic polymers as a single hybrid material can provides unique opportunities to combine properties of two individual components, with entirely new synergism. [15][16][17] The resultant hybrid materials may create a new class of nonbiological macromolecules which may mimic the biological structures and properties of amino acids as well as bioactivities of natural polysaccharides.…”

“…24 To have pH-responsive feature in the synthetic system, the utilization of biocompatible natural residues such as amino acids are much advantageous, compared to the other non-natural pH-responsive moieties. 13 Importantly, there are several reports available for the thermo-based stimuli responsive glycopolymers, 25,26 while the pH-based stimuli responsive glycopolymers are relatively unexplored. [27][28][29][30][31] In this context, we have revealed the feasibility of side-chain hybrid polymeric system comprised of both sugar and amino acid constituents with pH responsive property.…”

Fabrication and characterization of bifunctional spherical polyelectrolyte brushes

“…[1][2][3][4][5] They are widely applied in many fields, including biomaterials, sensor, drug delivery, and separation. [6][7][8][9][10][11] The spherical polyelectrolyte brushes (SPBs), prepared by photoemulsion polymerization, are stable colloid systems and sensitive to stimulations through functional polymer chains and modified cores. [4,[12][13][14][15] SPBs are classified into three kinds: anionic, cationic, and nonionic according to the changes of polymer chains.…”