Molecular‐Target‐Based Anticancer Photosensitizer: Synthesis and in vitro Photodynamic Activity of Erlotinib–Zinc(II) Phthalocyanine Conjugates

Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib–zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR‐overexpressing cancer cells owing to the presence of the small molecular‐target‐based anticancer agent erlotinib. All conjugates were found to be essentially non‐cytotoxic in the absence of light (up to 50 μM ), but upon illumination, they show significantly high photo‐cytotoxicity toward HepG2 cells, with IC₅₀ values as low as 9.61–91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm^?2). Structure–activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular‐target‐based photodynamic therapy.     

Amphiphilic star‐shaped poly(ε‐caprolactone)‐block‐poly(l‐lysine) copolymers with porphyrin core: Synthesis,self‐assembly,and cell viability assay

Star‐shaped copolymers poly(ε‐caprolactone)‐bolck‐poly(ε‐benzyloxycarbonyl‐l ‐lysine) (SPPCL‐b‐PZLLs) with porphyrin core were synthesized by a sequential ring‐opening polymerization (ROP) of CL and Nε‐Benzyloxycarbonyl‐l ‐lysine N‐Carboxyanhydride. After the deprotection of benzyloxycarbonyl groups in polylysine blocks, the star‐shaped amphiphilic copolymers SPPCL‐b‐PLLs were obtained. These amphiphilic copolymers can self‐assemble into micelles or aggregates in aqueous solution. Investigation shows that the morphology of micelles/aggregates varied according to the change of pH values of media, indicating the pH‐responsive property of SPPCL‐b‐PLL copolymers. Furthermore, associated with conjugated porphyrin cores, the SPPCL‐b‐PLL copolymers micelles showed a certain degree of Photodynamic Therapy (PDT) effects on tumor cells, suggesting its potential application as carrier for hydrophobic drug with additional therapeutic ability of inherent porphyrin segments. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40097.     

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis,Spectroscopy, Photophysics,and in vitro Photosensitizing Efficacy

Chlorin and bacteriochlorin derivatives of 5,10,15,20‐tetrakis(2‐chloro‐5‐sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK‐MEL‐188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time‐dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.     

Self‐assembled nanoparticles from folate‐decorated maleilated pullulan–doxorubicin conjugate for improved drug delivery to cancer cells

The goal of this study was to develop doxorubicin conjugate nanoparticles with increased antitumor effects, reduced side effects and the ability to overcome multidrug resistance (MDR). In this regard, folate‐decorated maleilated pullulan–doxorubicin conjugate nanoparticles were developed as carriers for co‐delivery of pyrrolidinedithiocarbamate and doxorubicin (FA‐MP‐DOX/PDTC + DOX NPs). The resultant nanoparticles showed spherical geometry, with an average diameter of 152 nm. The two drugs were released from the nanoparticles in a slow, pH‐dependent sustained release. To test the efficacy of these nanoparticles, in vitro tests including cell viability and folate receptor‐mediated endocytosis were conducted against both A2780 cells and A2780/DOX^R cells. Compared to free DOX, the FA‐MP‐DOX/PDTC + DOX NPs showed effective but less potent cytotoxicity against A2780 cells. For A2780/DOX^R cells, they showed enhanced cellular uptake, increased targeting capacity and cytotoxicity. These results suggest that co‐delivery of PDTC and DOX may further overcome MDR by transporting an increased amount of DOX within cells in addition to the folate receptor‐mediated endocytosis process. © 2012 Society of Chemical Industry     

Macromolecular Uptake of Alkyl‐Chain‐Modified Guanidinoglycoside Molecular Transporters

Guanidinoglycosides, a family of cellular transporters capable of delivering high M_w biopolymers, have previously been shown to display high selectivity for cell‐surface heparan sulfate proteoglycans and promote their clustering. Herein, the internalization mechanism of amphiphilic guanidinoglycoside derivatives was investigated by cell‐surface FRET analysis. Unexpectedly, although the heparan sulfate selectivity is maintained, the cellular uptake of these derivatives does not appear to involve clustering of the proteoglycans on the cell surface. This suggests a distinct uptake mechanism when compared to the parent guanidinoglycoside‐based carriers.     

Photocontrol of Protein Activity in Cultured Cells and Zebrafish with One‐ and Two‐Photon Illumination

We have implemented a noninvasive optical method for the fast control of protein activity in a live zebrafish embryo. It relies on releasing a protein fused to a modified estrogen receptor ligand binding domain from its complex with cytoplasmic chaperones, upon the local photoactivation of a nonendogenous caged inducer. Molecular dynamics simulations were used to design cyclofen‐OH, a photochemically stable inducer of the receptor specific for 4‐hydroxy‐tamoxifen (ER^T2). Cyclofen‐OH was easily synthesized in two steps with good yields. At submicromolar concentrations, it activates proteins fused to the ER^T2 receptor. This was shown in cultured cells and in zebrafish embryos through emission properties and subcellular localization of properly engineered fluorescent proteins. Cyclofen‐OH was successfully caged with various photolabile protecting groups. One particular caged compound was efficient in photoinducing the nuclear translocation of fluorescent proteins either globally (with 365 nm UV illumination) or locally (with a focused UV laser or with two‐photon illumination at 750 nm). The present method for photocontrol of protein activity could be used more generally to investigate important physiological processes (e.g., in embryogenesis, organ regeneration and carcinogenesis) with high spatiotemporal resolution.     

Synthesis and photo‐polymerization of bio‐based furanic compounds functionalized by 2‐hydroxypropyl methacrylate group(s)

Bio‐based compounds (FmHPM and FdHPM) with a furan backbone and photo‐polymerizable 2‐hydroxypropyl methacrylate (HPM) group(s) were synthesized from carbohydrate‐derived furanyl alcohols (furan‐2‐methanol and furan‐2,5‐dimethanol) and their photo‐polymerizing behaviors and mechanical properties after photo‐polymerization were investigated. Half time values (t_1/2) of bio‐based FmHPM and FdHPM were 10.4 s and 3.0 s and their shrinkage ratios were 3.0 and 6.1% during photo‐polymerization, respectively. Tensile‐shear strength of glass and polycarbonate joints bonded by bio‐based furanic compounds appeared in range of 0.2–0.6 MPa and pencil hardness of film coated by bio‐based furanic compounds after photo‐polymerization showed 2H–3H. Newly synthesized bio‐based furanic compounds allowed the feasibility to alternate petroleum‐based Bis‐GMA/TEGDMA, photo‐polymerizable composition widely utilized in a variety of applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

A Molecular Hybrid for Mitochondria‐Targeted NO Photodelivery

The design, synthesis, spectroscopic and photochemical properties, and biological evaluation of a novel molecular hybrid that is able to deliver nitric oxide (NO) into mitochondria are reported. This molecular conjugate unites a tailored o‐CF₃‐p‐nitroaniline chromophore, for photo‐regulated NO release, and a rhodamine moiety, for mitochondria targeting, in the same molecular skeleton via an alkyl spacer. A combination of steady‐state and time‐resolved spectroscopic and photochemical experiments demonstrate that the two chromogenic units preserve their individual photophysical and photochemical properties in the conjugate quite well. Irradiation with violet light triggers NO release from the nitroaniline moiety and photoionization in the rhodamine center, which also retains considerable fluorescence efficiency. The molecular hybrid preferentially accumulates in the mitochondria of A549 lung adenocarcinoma cells where it induces toxicity at a concentration of 1 μm , exclusively upon irradiation. Comparative experiments, carried out with ad‐hoc‐synthesized model compounds, suggest that the phototoxicity observed at such a low concentration is probably not due to NO itself, but rather to the formation of the highly reactive peroxynitrite that is generated from the reaction of NO with the superoxide anion.     

Fabrication of thermoresponsive,core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Thermoresponsive amphiphilic copolymer, poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} with a branched structure was designed and synthesized by consecutive reversible addition–fragmentation chain‐transfer polymerization. The further hydrolysis of trimethoxysilyl functions in 3‐(trimethoxysilyl) propyl methacrylate units led to the fabrication of core‐crosslinked (CCL) micelles with silica crosslinks at temperatures above the lower critical solution temperature of the poly(N‐isopropyl acrylamide) block. The thermally induced structural and morphological changes of the CCL micelles in aqueous solution were investigated by transmission electron microscopy and ¹H‐NMR analyses. The resulting CCL micelles were further explored as nanocarriers for the codelivery of an anticancer drug and nucleic acid for enhanced therapeutic efficacy. The CCL micelles effectively condensed the nucleic acid and mediated higher gene transfer in the presence of serum than in serum‐free transduction. A cytotoxicity study revealed that whereas the pure CCL micelles exhibited unapparent cytotoxicity, the codelivery of p53 and doxorubicin with the CCL micelle formulation resulted in better treatment efficiency than sole chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41752.     

Vesicular and micellar self‐assembly of stimuli‐responsive poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) amphiphilic diblock copolymers

Dually responsive amphiphilic diblock copolymers consisting of hydrophilic poly(N‐isopropyl acrylamide) [poly(NIPAAm)] and hydrophobic poly(9‐anthracene methyl methacrylate) were synthesized by reversible addition fragmentation chain‐transfer (RAFT) polymerization with 3‐(benzyl sulfanyl thiocarbonyl sulfanyl) propionic acid as a chain‐transfer agent. In the first step, the poly(NIPAAm) chain was grown to make a macro‐RAFT agent, and in the second step, the chain was extended by hydrophobic 9‐anthryl methyl methacrylate to yield amphiphilic poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) block copolymers. The formation of copolymers with three different hydrophobic block lengths and a fixed hydrophilic block was confirmed from their molecular weights. The self‐assembly of these copolymers was studied through the determination of the lower critical solution temperature and critical micelle concentration of the copolymers in aqueous solution. The self‐assembled block copolymers displayed vesicular morphology in the case of the small hydrophobic chain, but the morphology gradually turned into a micellar type when the hydrophobic chain length was increased. The variations in the length and chemical composition of the blocks allowed the tuning of the block copolymer responsiveness toward both the pH and temperature. The resulting self‐assembled structures underwent thermally induced and pH‐induced morphological transitions from vesicles to micelles and vice versa in aqueous solution. These dually responsive amphiphilic diblock copolymers have potential applications in the encapsulation of both hydrophobic and hydrophilic drug molecules, as evidenced from the dye encapsulation studies. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46474.     

Application of microwave‐assisted click chemistry in the preparation of functionalized copolymers for drug conjugation

The aim of this study is to develop azido‐carrying biodegradable polymers and their postfunctionalization with alkynyl compounds via click chemistry and to investigate their potential use in drug delivery. Azido polymers were prepared by ring‐opening polymerization of cyclic carbonate monomer, 2,2‐bis(azidomethyl)trimethylene carbonate (ATC) with lactide using stannous octoate as catalyst. Several alkynyl compounds were selected to investigate the feasibility and reaction condition of click chemistry. With microwave‐assisting, the reaction time of click chemistry was shortened to 5 min. By using poly(ethylene glycol) (PEG) as macroinitiator, amphiphilic block copolymer mPEG‐b‐P(LA‐co‐ATC) was obtained and it could self‐assemble into micelles by solvent replacement method. The pendant groups were used for conjugating anticancer drugs gemcitabine and paclitaxel and fluorescent dye Rhodamine B. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide was used to assay the cytotoxicity of the conjugate micelles against SKOV‐3 and HeLa cell lines. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Recent advances and potential applications of the photo‐induced macroscopic response of self‐assembled azopolymer in aqueous media

This mini‐review highlights issues related to the photo‐triggered macroscopic response of azopolymer in supramolecular hydrogel and polymer vesicles. Cyclodextrin (CD) can form an inclusion complex with trans‐azobenzene while cis‐azobenzene is expelled out of the CD's cavity. This photo‐reversible supramolecular host ? guest interaction is used to trigger sol ? gel transitions and to induce macroscopic assembly. When substituted azobenzene is located at chain ends of linear polyethylene glycol, monodisperse vesicles are formed exhibiting a photo‐induced pulsating behavior. The macroscopic phase transition and assembly or pulsating behavior of azopolymers can be expected to have potential applications as smart biomedical materials. © 2014 Society of Chemical Industry     

A New Thermo‐, pH‐ and CO2‐Responsive Fluorescent Four‐Arm Star Polymer with Aggregation‐Induced Emission for Long‐Term Cellular Tracing

Development of fluorescent bioprobes for long‐term cell tracking is of great importance to monitor the processes of genesis, development, invasion, and metastasis of cancerous cells. Herein, a new multistimuli‐responsive star polymer of tetraphenylethene‐graft‐tetra‐poly[N‐[2‐(diethylamino)‐ethyl]acrylamide] (TPE‐tetraPDEAEAM) with aggregation‐induced emission (AIE) effect for tracing live cells over a long period of time is synthesized by atom transfer radical polymerization using TPE derivative as initiator. TPE‐tetraPDEAEAM gives both lower critical solution temperature and fluorescence responses to the stimulus of the temperature, pH, and CO₂ by combining the thermoresponsive and pH/CO₂‐responsive moieties of the diethylamino and acrylamide groups. The AIE‐active TPE‐tetraPDEAEAM has the advantages of very low cytotoxicity, efficient cellular uptake, and strong fluorescence of polymer‐treated cells, which ensure its good performance in long‐term cell tracing. This facile tracking of HeLa cells for as long as nine passages exhibits superior performance in long‐term cell tracing as compared with some commercial cell tracing probes.     

Plasmon‐enhanced,two‐photon absorption in Schiff‐base‐modified poly(styrene‐co‐maleic anhydride)–gold nanocomposites

Poly(styrene‐co‐maleic anhydride) (SMA) is a synthetic copolymer with interesting thermal and membrane properties. Schiff bases are one of the most widely used organic compounds with chelating ligands having N, S, and O as donor atoms. A Schiff‐base‐modified SMA was synthesized by the reaction of the copolymer with salicylaldehyde thiosemicarbazone. Gold (Au) nanoparticles (NPs), synthesized by a citrate reduction method were used to prepare the polymer–Au nanocomposites. In this research, we explored and investigated the effects on the linear and nonlinear optical properties of the Schiff‐base‐modified SMA copolymer with the incorporation of Au NPs. Open‐aperture Z‐scan measurements were recorded for the polymer, modified polymer, and polymer–Au nanocomposites at 532 nm with an Nd:YAG laser with a repetition rate of 10 Hz and a pulse width of 5 ns. The results indicate that the addition of the Au NPs effectively enhanced the two‐photon absorption coefficients of the polymer and, thereby, provided a platform for the development of nonlinear optical devices with good optical‐limiting properties. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45377.     

“One‐pot” synthesis of well‐defined functional copolymer and its application as tumor‐targeting nanocarrier in drug delivery

A one‐pot synthesis is developed for PEG₆₀₀‐b‐poly(glycerol monoacrylate) (PEG₆₀₀‐b‐PGA), by which folate and superparamagnetic iron oxide nanoparticles (SPIONs) are assembled to form folic acid‐conjugated magnetic nanoparticles (FA‐MNPs) as a tumor targeting system. The synthesis consists of a “click” reaction and atom transfer radical polymerization (ATRP) to obtain the well‐defined furan‐protected maleimido‐terminated PEG₆₀₀‐b‐poly(solketal acrylate) (PEG₆₀₀‐b‐PSA) copolymer. After deprotection, the key copolymer N‐maleimido‐terminated PEG₆₀₀‐b‐PGA is successfully conjugated with thiol derivatives of folate and FITC, respectively. FA‐MNPs are developed by assembling of the resulting polymer FA‐PEG₆₀₀‐b‐PGA with SPIONs, and characterized for their size, surface charge, and superparamagnetic properties. To investigate the cellular uptake of the nanoparticles by Hela cells and φ2 cells using fluoresce technique, FA‐FITC‐MNPs are also obtained by assembling of FA‐PEG₆₀₀‐b‐PGA, FITC‐PEG₆₀₀‐b‐PGA with SPIONs. Qualitative and quantitative determinations of FA‐FITC‐MNPs show that the particles specifically internalized to Hela cells. No significant cytotoxicity is observed for these two kinds of cell lines. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40405.     

Photo‐curing behaviors of bio‐based isosorbide dimethacrylate by irradiation of light‐emitting diodes and the physical properties of its photo‐cured materials

Bio‐based isosorbide (1,4:3,6‐dianhydroglucitol), which was obtained from biomass‐derived carbohydrates, has recently attracted much attention as an alternative to bisphenol A (BPA) because of its rigidity and transparency. BPA is still widely used for a variety of chemical applications even though it is known to be an endocrine‐disrupting chemical. BPA is a key precursor to most photo‐curable materials ranging from encapsulants of electronic devices to dental sealants. In this study, photo‐curable isosorbide dimethacrylate (ISDM) was synthesized from bio‐based isosorbide as a substitute for BPA, and the photo‐curing behaviors of ISDM by irradiation with light‐emitting diode (LED) light were investigated. The photo‐curing conversion and rates of ISDM formation were determined based on the change in the peak corresponding to the double bond within the methacrylate groups using attenuated total reflectance Fourier transform infrared (ATR–FTIR) spectroscopy. The effects of initiators and the wavelength of LED light on the photo‐curing conversion and rates of ISDM formation were examined, and a comparative study was carried out with 2,2‐bis[4(2‐hydroxy‐3‐methacryloyloxy‐propyloxy)phenylpropane] (Bis‐GMA), which is a photo‐curing material bearing a BPA moiety. In addition, the mechanical properties, such as surface hardness, adhesion strength, and transparency, after photo‐curing of ISDM were evaluated. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42726.     

Thermal and mechanical properties of nanocomposites based on a PLLA‐b‐PEO‐b‐PLLA triblock copolymer and nanohydroxyapatite

Composites which combine biocompatible polymers and hydroxyapatite are unique materials with regards to their mechanical properties and bioactivity in the development of temporary bone‐fixation devices. Nanocomposites based on a biocompatible and amphiphilic triblock copolymer of poly(l‐ lactide) (PLLA) and poly(ethylene oxide) (PEO) —PLLA‐b‐PEO‐b‐PLLA— and neat (nHAp) or PEO‐modified (nHAp@PEO) hydroxyapatite nanoparticles were prepared by dispersion in benzene solutions, followed by freeze‐drying and injection moulding processes. The morphology of the copolymers of a PEO block dispersed throughout a PLLA matrix was not changed with addition of the nanofillers. The nHAp particles were spherical and, after modification, the nHAp@PEO nanoparticles were partially agglomerated. In the nanocomposites, these particles characteristics remained unchanged, and the nHAp particles and nHAp@PEO agglomerates were uniformly dispersed through the copolymer matrix. These particles acted as nucleating agents, with nHAp@PEO being more efficient. The incorporation of nHAp increased both the reduced elastic modulus (～22%) and the indentation hardness (～15%) in comparison to the copolymer matrix, as determined by nanoindentation tests, while nHAp@PEO addition resulted in lower increments of these mechanical parameters. The incorporation of untreated nHAp was, therefore, more beneficial with regards to the mechanical properties, since the amphiphilic PLLA‐b‐PEO‐b‐PLLA matrix was already efficient for nHAp nanoparticles dispersion. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44187.     

Preparation and characterization of magnetic star‐shaped amphiphilic copolymer nanoparticles of S‐Fe3O4‐PLA‐b‐MPEG

Magnetic star‐shaped amphiphilic copolymers (S‐Fe₃O₄‐PLA‐b‐MPEG) consisting of Fe₃O₄ as the core, poly(L ,D ‐lactide) (PLA) as the inner layer, and monomethyl polyethylene glycol (MPEG) as the out shell were synthesized. The syntheses included ring‐opening polymerization of L ,D ‐lactide initiated by hydroxyl modified Fe₃O₄ (Fe₃O₄‐(OH) _n), followed by the esterification of the PLA with MPEG. The structure of the star block copolymers were characterized by Fourier Transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, transmission electron microscopy, nanoparticle size analyzer, and vibrating sample magnetometer. The nanoparticles in aqueous solution were made from the amphiphilic star copolymer. The average size of the nanoparticles was adjustable and increased with the increase of the PLA segments in the copolymer. The cytotoxicity grade of the nanoparticles was zero determined by the analysis of cytotoxicity. The nanoparticles could potentially be used as the drug vehicles for magnetic‐response controlled release. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers     

Synthesis and Evaluation of Glycoconjugates Comprising N‐Acyl‐Modified Thomsen–Friedenreich Antigens as Anticancer Vaccines

Thomsen–Friedenreich (TF) antigen is an important tumor‐associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N‐acyl‐modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross‐reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross‐reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF‐positive tumor cells (4T1). In particular, the N‐monofluoroacetyl‐modified TF conjugate 4 ‐CRM197 showed the strongest complement‐dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.     

Properties of new cationic amphiphilic polymers in hydro‐alcoholic media

BACKGROUND: Following our recent synthesis and characterization of three new families of cationic amphiphilic polymers with great structural variability, this paper reports their physical chemical properties in aqueous media in relation to their chemical structure. These amphiphilic polymers are comb poly(meth)acrylamides laterally substituted by groups containing a quaternary ammonium site and hydrophobic n‐alkyl side chains with variable lengths. RESULTS: Viscometry first showed that these polymers display typical polysoap behaviour in hydro‐alcoholic mixtures. Fluorescence spectrometry was then used to characterize the corresponding intramolecular association with two complementary fluorescent probes. In addition to confirming macromolecular folding, pyrene provided information about the probe local environment polarity whereas a molecular rotor gave interesting complementary information about the compactness of the corresponding nano‐domains. CONCLUSION: It was shown that increasing the length of the n‐alkyl side chain induced much better polysoap properties whereas increasing the size of the spacer between the two polar amide and ammonium groups and the presence of a methyl side group had the greatest impact on the nano‐domain characteristics. Copyright © 2009 Society of Chemical Industry