Poly (acrylic acid) (PAA), an anionic polymer was used to prepare ion pair self-assembly (IPSAM) with 4-(methylthio)aniline (MTA), a hydrophobic counter ion, which is responsive to temperature and oxidation. The IPSAM was formed when the carboxylic to amino group molar ratio was 7/3-5/5. The structure of the IPSAM nanoparticle was spherical whose diameter was 30-40 nm on the TEM images. The PAA/MTA ion pair showed the upper critical solution temperature (UCST) that hiked with increasing MTA content. When the MTA of the ion pair was oxidized by H2O2, the UCST was also increased. The amphiphilic property of the ion pair was responsible for interface activity which declined upon the oxidation of the MTA. The surface tension was low for the ratio of PAA/MTA (5/5), which made the 5/5 ratio suitable for further studies. The interaction between PAA and MTA, which was ionic, and the oxidation of MTA was confirmed by FT-IR spectroscopy. The release of payload (i.e. Nile red) in IPSAM was restrained below the UCST but it was triggered above the phase transition temperature possibly due to the disintegration of the IPSAM whereas on MTA oxidation the release was shielded due to more hydrophobicity. The release was found to be higher in tumor environment temperature which could be controlled with the input concentration of H2O2 giving a stable IPSAM. The cell viability results showed that IPSAM has no significant cytotoxicity and can serve as a drug carrier for stimulus-response.
ArkabanHBaraniMAkbarizadehMR, et al.Polyacrylic acid nanoplatforms: antimicrobial, tissue engineering, and cancer theranostic applications. Polymers2022; 14: 1259.
2.
XuMZhuJWangF, et al.Improved in vitro and in vivo biocompatibility of graphene oxide through surface modification: poly(acrylic acid)-functionalization is superior to PEGylation. ACS Nano2016; 10: 3267–3281.
3.
JiaXYinJHeD, et al.Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging. J Biomed Nanotechnol2013; 9: 2063–2072.
4.
KadlubowskiSGrobelnyJOlejniczakW, et al.Pulses of fast electrons as a tool to synthesize poly(acrylic acid) nanogels. Intramolecular cross-linking of linear polymer chains in additive-free aqueous solution. Macromolecules2003; 36: 2484–2492.
5.
KhanlariSDubéMA. Bioadhesives: a review. Macromol React Eng2013; 7: 573–587.
6.
DaiYZhangCChengZ, et al.pH-responsive drug delivery system based on luminescent CaF2:Ce3+/Tb3+-poly(acrylic acid) hybrid microspheres. Biomaterials2012; 33: 2583–2592.
7.
JiangLGaoLWangX, et al.The application of mucoadhesive polymers in nasal drug delivery. Drug Dev Ind Pharm2010; 36: 323–336.
8.
SwilemAEElshazlyAHMHamedAA, et al.Nanoscale poly(acrylic acid)-based hydrogels prepared via a green single-step approach for application as low-viscosity biomimetic fluid tears. Mater Sci Eng C2020; 110: 110726.
9.
MaalekipourMSafariMBarekatainM, et al.Effect of adhesive resin as a modeling liquid on elution of resin composite restorations. Int J Dent2021; 2021: 1–9.
10.
RoostaeeMSheikhshoaieI. Fabrication of a sensitive sensor for determination of xanthine in the presence of uric acid and ascorbic acid by modifying a carbon paste sensor with Fe3O4@Au core–shell and an ionic liquid. J Food Meas Charact2022; 16: 731–739.
11.
RivasB. Water-soluble polymer–metal ion interactions. Prog Polym Sci2003; 28: 173–208.
12.
SethyPKMohapatraPPatraS, et al.Antimicrobial and barrier properties of polyacrylic acid/GO hybrid nanocomposites for packaging application. Nano-Structures & Nano-Objects2021; 26: 100747.
13.
ZhaoGHuangYMeiC, et al.Chiral nematic coatings based on cellulose nanocrystals as a multiplexing platform for humidity sensing and dual anticounterfeiting. Small2021; 17: 2103936.
14.
LiuHChenHCaoF, et al.Amphiphilic block copolymer poly (acrylic acid)-B-polycaprolactone as a novel pH-sensitive nanocarrier for anti-cancer drugs delivery: in-vitro and in-vivo evaluation. Polymers2019; 11: 820.
15.
PásztorSIvánBKaliG. Extreme difference of polarities in a single material: poly(acrylic acid)-based amphiphilic conetworks with polyisobutylene cross-linker. J Polym Sci Part A Polym Chem2017; 55: 1818–1821.
16.
SantosSMedronhoBSantosT, et al.Amphiphilic molecules in drug delivery systems. Berlin, Germany: Springer, 2013, pp. 35–85.
17.
ZhuYWangXZhangJ, et al.Exogenous vitamin C boosts the antitumor efficacy of paclitaxel containing reduction-sensitive shell-sheddable micelles in vivo. J Control Release2017; 250: 9–19.
18.
KimTHAlleMParkSC, et al.Self-assembly prepared using an ion pair of poly(ethylene imine) and (phenylthio) acetic acid as a drug carrier for oxidation, temperature, and NIR-responsive release. Chem Eng J2021; 415: 128954.
19.
YanRHuYLiuF, et al.Activatable NIR fluorescence/MRI bimodal probes for in vivo imaging by enzyme-mediated fluorogenic reaction and self-assembly. J Am Chem Soc2019; 141: 10331–10341.
20.
KimJAYoonDYKimJ-C. Oxidation-triggerable liposome incorporating poly(hydroxyethyl acrylate-co-allyl methyl sulfide) as an anticancer carrier of doxorubicin. Cancers2020; 12: 180.
21.
CiferriAPericoA (eds) Ionic interactions in natural and synthetic macromolecules. Hoboken: Wiley, 2012. Epub ahead of print. DOI: 10.1002/9781118165850.
22.
KriwetBWalterEKisselT. Synthesis of bioadhesive poly(acrylic acid) nano- and microparticles using an inverse emulsion polymerization method for the entrapment of hydrophilic drug candidates. J Control Release1998; 56: 149–158.
23.
MorimotoKIwamotoTMorisakaK. Possible mechanisms for the enhancement of rectal absorption of hydrophilic drugs and polypeptides by aqueous polyacrylic acid gel. J Pharmacobio-Dyn1987; 10: 85–91.
24.
LiuXHuDJiangZ, et al.Multi-stimuli-responsive amphiphilic assemblies through simple postpolymerization modifications. Macromolecules2016; 49: 6186–6192.
25.
WangYWengJWenX, et al.Recent advances in stimuli-responsive in situ self-assembly of small molecule probes for in vivo imaging of enzymatic activity. Biomater Sci2021; 9: 406–421.
26.
GantaSDevalapallyHShahiwalaA, et al.A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release2008; 126: 187–204.
27.
ZhuangJGordonMRVenturaJ, et al.Multi-stimuli responsive macromolecules and their assemblies. Chem Soc Rev2013; 42: 7421.
28.
López RuizARamirezAMcEnnisK. Single and multiple stimuli-responsive polymer particles for controlled drug delivery. Pharmaceutics2022; 14: 421.
ManoJF. Stimuli-responsive polymeric systems for biomedical applications. Adv Eng Mater2008; 10: 515–527.
31.
LiXLiuJLiD, et al.Bioinspired multi-stimuli responsive actuators with synergistic color- and morphing-change abilities. Adv Sci2021; 8: 2101295.
32.
WellsCMHarrisMChoiL, et al.Stimuli-responsive drug release from smart polymers. J Funct Biomater2019; 10: 34.
33.
LeNTTNguyenTNQCaoDuV, et al.Recent progress and advances of multi-stimuli-responsive dendrimers in drug delivery for cancer treatment. Pharmaceutics2019; 11: 591.
34.
ParkSHKimJ-C. Monoolein cubic phase containing poly(hydroxyethyl acrylate-co-propyl methacrylate-co-methacrylic acid) and its electric field-driven release property. J Ind Eng Chem2019; 70: 226–233.
35.
KimTHLeeS-HKimJ-C. Spray-dried microparticles composed of carboxylated cellulose nanofiber and cysteamine and their oxidation-responsive release property. Colloid Polym Sci2020; 298: 157–167.
36.
LongWKimJ-C. Electric field-responsive ion pair self-assembly. Int J Polym Mater Polym Biomater2023; 72: 485–496.
37.
ParkSCKimJ-C. Monoolein cubic phase incorporating poly(dimethylaminoethyl methacrylate- co -phenyl vinyl sulfide) and its hydrogen peroxide, temperature, and near infrared-responsive release properties. Int J Polym Mater Polym Biomater. 2023; 1–16.
38.
ParkSCSharmaGKimJ-C. Temperature- and oxidation-dependent doxorubicin release from poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) cryogel. Colloid Polym Sci2023; 301: 331–345.
39.
ZhaoFSharmaGKimJ-C. Temperature and oxidation-sensitive dioleoylphosphatidylethanolamine liposome stabilized with poly(ethyleneimine)/(phenylthio)acetic acid ion pair. J Biomater Sci Polym Ed2023; 34: 632–649.
40.
ChengRMengFDengC, et al.Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials2013; 34: 3647–3657.
41.
JiaZWongLDavisTP, et al.One-pot conversion of RAFT-generated multifunctional block copolymers of HPMA to doxorubicin conjugated acid- and reductant-sensitive crosslinked micelles. Biomacromolecules2008; 9: 3106–3113.
42.
ReddyPGMamidiNPradeepCP. An organic–inorganic hybrid supramolecular framework material based on a [P 2 W 18 O 62 ] 6− cluster and Yb & Na complexes of pyridine-2,6-dicarboxylic acid: a catalyst for selective oxidation of sulfides in water with H 2 O 2. CrystEngComm2016; 18: 4272–4276.
43.
WangpimoolKRanaKKimJ-C. Temperature and oxidation-responsive ion pair self-assembly composed of hydroxyethyl cellulose ethoxylate and phenylthio acetic acid. Cellulose2023; 30: 1–16. Epub ahead of print 24 July 2023. DOI: 10.1007/s10570-023-05375-6
44.
ZhangHKimJ-C. Reduction-responsive monoolein cubic phase containing hydrophobically modified poly(ethylene imine) and dithiodipropionic acid. Colloids Surfaces A Physicochem Eng Asp2016; 506: 526–534.
45.
LeeJSFeijenJ. Polymersomes for drug delivery: design, formation and characterization. J Control Release2012; 161: 473–483.
46.
MukherjeeSRaghuramanHChattopadhyayA. Membrane localization and dynamics of nile red: effect of cholesterol. Biochim Biophys Acta - Biomembr2007; 1768: 59–66.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
