Polydopamine Nanoparticle as a Multifunctional Nanocarrier for Combined Radiophotodynamic Therapy of Cancer

Combination of different therapeutic strategies to treat cancer has attracted tremendous attention in recent years. Herein, the authors develop polydopamine (PDA) nanoparticles with polyethylene glycol (PEG) modification as a multifunctional nanocarrier for coloading photosensitizer chlorine6 (Ce6) and curcumin (Cur) for combined photodynamic therapy (PDT) and radiotherapy (RT) of cancer. PEGylated PDA nanoparticles (PDA‐PEG) exhibit well water soluble and biocompatible in different physiological solutions and cause no obvious toxicity to cancer cells. In this nanoparticle, the loaded Ce6 can trigger the generation of single oxygen under near‐infrared laser irradiation for PDT, while the loaded Cur can act as an excellent radiosensitizer under X‐ray irradiation for enhanced external RT. As demonstrated by in vitro and in vivo therapeutic efficiency, combined PDT and RT based on PDA‐PEG/Cur/Ce6 nanoparticles exhibits significant inhibition the growth of cancer cells, revealing perfect performance in cancer treatment. Therefore, the study not only presents a polymer‐based theranostic platform for cancer treatment but also demonstrates the potential applications of combined RT and PDT for the future clinic cancer therapy.     

An investigation into the role of macromolecules of different polarity as passivating agent on the physical,chemical and structural properties of fluorescent carbon nanodots

In this study, comparative evaluation of fluorescent carbon nanodots (C-Dots) prepared using carob molasses was reported by screening various biocompatible macromolecules as passivating agent (PA). Incorporation of PAs with different molecular weight, polarity, and chemical structure was examined, and compared with the polyethylene glycol (PEG, Mn = 10 kN) passivated and pristine C-Dots. Not only the fluorescence properties but also many other features including size, crystal structure, colloidal conductivity, resistance to photobleaching, quantum yield, and UV-modulated surface interaction of them with the reactive oxygen species (ROS) as well as ROS production were investigated. Photoluminescence (PL) capacity of C-Dots was found to be associated with the number of surface alkyl groups and polymeric hydrogen bounding present on the C-Dot surface (increased number is associated with decreased PL) while surface conductivity of C-Dots in water was proportional to the PL intensity. More importantly, C-Dots with relatively poorer fluorescent were investigated in various organic solvents (hexane, methanol, acetone, ethanol, dimethylformamide (DMF), and DMSO). As happens with the fluorescent dyes, their PL intensities were significantly enhanced (even for pristine C-Dots) depending on the solvent characteristics. All of the C-Dots synthesized were further evaluated by means of UV-induced generation of ROS and inhibition of ROS by using H₂O₂ as model. In contrary to other carbonaceous nanomaterials, they did not show any ROS generation, on the contrary, they showed ROS scavenging activity that can be modulated by UV-irradiation (λ _exc = 365 nm). PEG and alginate passivated C-Dots inhibited H₂O₂ activity at LC₅₀ values below 10 mg/mL.

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Glutathione‐Mediated Degradation of Surface‐Capped MnO2 for Drug Release from Mesoporous Silica Nanoparticles to Cancer Cells

Owing to its higher concentration in cancer cells than that in the corresponding normal cells, glutathione (GSH) provides an effective and flexible mechanism to design drug delivery systems. Here a novel GSH‐responsive mesoporous silica nanoparticle (MSN) is reported for controlled drug release. In this system, manganese dioxide (MnO₂) nanostructure, formed by the reduction of KMnO₄ on the surface of carboxyl‐functionalized MSN can block the pores (MSN@MnO₂). By a redox reaction, the capped MnO₂ nanostructure can dissociate into Mn²⁺ in the presence of GSH molecules. The blocked pores are then uncapped, which result in the release of the entrapped drugs. As a proof‐of‐concept, doxorubicin (DOX) as model drug is loaded into MSN@MnO₂. DOX‐loaded MSN@MnO₂ shows an obvious drug release in 10 × 10^?3 m GSH, while no release is observed in the absence of GSH. In vitro studies using human hepatocellular liver carcinoma cell line (HepG2) prove that the DOX‐loaded MSN@MnO₂ can entry into HepG2 cells and efficiently release the loaded DOX, leading to higher cytotoxicity than to that of human normal liver cells (L02). It is believed that further developments of this GSH‐responsive drug delivery system will lead to a new generation of nanodevices for intracellular controlled delivery.     

Analysis of the optical properties of poly(3‐octylthiophene) partially dedoped

In this work, poly(3‐octylthiophene) (P3OT) films were synthesized electrochemically in non‐aqueous media through the oxidation of the monomer, (3‐octylthiophene), using a standard three‐electrode cell in acetonitrile with 0.05 mol L^?1 LiClO₄ or 0.05 mol L^?1 Et₄NBF₄. The polymeric films were deposited on fluorine tin oxide (FTO). The partial dedoping was obtained in NH₄OH solution, providing a good chemical stability of the formed material. The films obtained through this method have been characterized by Fourier‐transform infrared spectroscopy (FT‐IR), electron paramagnetic resonance (EPR), UV–Vis absorption, and photoluminescence (PL) spectroscopy. The FT‐IR and EPR spectra together gave the results that led to characterization of two structures (pristine and non‐pristine forms of thiophene rings) while forming the P3OT polymer chain. These results were associated with the stabilization of pristine chains and mixed chains (non‐pristine structures) in the polymeric film. Their bands in the PL spectra are wide and asymmetric and their adjustments by Gaussian functions was necessary; this was the main indication that there are two distinct contributions to the emission spectra. These two contributions are attributed to the emission by mixed chains (Gaussian centered at higher energy) and by pristine chains (Gaussian of lower energy) present in the formed polymeric material. Copyright © 2010 John Wiley & Sons, Ltd.     

Uptake and Intracellular Fate of Peptide Surface‐Functionalized Silica Hybrid Magnetic Nanoparticles In Vitro

Recently, the use of nanomaterials as intracellular targeting tools for theranostics has gained heightened interest. Despite the clear advantages posed by surface‐functionalized nanoparticles (NPs) in this regard, limited understanding currently exists due to difficulties in reliably synthesizing NPs with surface functionalizations adequate for use in such applications, as well as the manner of analytics used to assess the cellular uptake and intracellular localization of these NPs. In the present study, two key surface functionalities (a nuclear localization sequence (NLS) and integrin‐ligand (cRGD)) are attached to the surface of multifunctional, silica hybrid magnetic nanoparticles (SHMNPs) containing a polyethylene glycol (PEG) polymer coating using a well‐described, reliable, and reproducible microreactor set‐up. Subsequent analytical interpretation, via laser scanning confocal, transmission electron and dark‐field microscopy, as well as flow cytometry, of the interaction of SHMNPs‐PEG‐cRGD‐NLS with macrophage (J774A.1) and epithelial (HeLa) cells shows internalization of the SHMNPs‐PEG‐cRGD‐NLS in both cell types up to 24 h after 20 μg mL^?1 exposure, as well as increasing aggregation inside of vesicles over this time period. The findings of this study show that by incorporating a variety of state‐of‐the‐art analytical and imaging approaches, it is possible to determine the specific effectiveness of surface peptide and ligand sequences upon multifunctional SHMNPs.     

Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents

Imaging guided combined therapy has attracted great attention in recent years. This study develops core–shell Au@FeS nanoparticles with polyethylene glycol (PEG) coating as multifunctional nanotheranostic agent for tumor imaging and combined photothermal therapy (PTT) and radiotherapy (RT). In this Au@FeS nanostructure, the gold core can act as a radiosensitizer for enhanced RT, while FeS shell offers contrast for T2‐weighted magnetic resonance imaging and endows the nanoparticles with strong high near‐infrared (NIR) for photoacoustic imaging and PTT. As demonstrated by both in vitro and in vivo experiments, Au@FeS‐PEG can act as excellent therapeutic agent for cancer synergistic treatment. More importantly, mild PTT boosts the blood flow into tumor and increases oxygenation to overcome the tumor hypoxia microenvironment, further enhancing the efficacy of RT. Moreover, Au@FeS‐PEG induces on obvious toxicity at a high dose (20 mg kg^?1) to the treated mice as evidenced by blood biochemistry. Therefore, this study brings an excellent strategy for cancer enhanced RT through NIR‐triggered mild PTT to overcome hypoxia‐associated radioresistance.     

Polymeric Micelles Employing Platinum(II) Linker for the Delivery of the Kinase Inhibitor Dactolisib

Polymeric micelles are attractive nanocarriers for hydrophobic drug molecules such as the kinase inhibitor dactolisib. Two different poly(ethylene glycol)–poly(acrylic acid) (PEG‐b‐PAA) block‐copolymers are synthesized, PEG(5400)‐b‐PAA(2000) and PEG(10000)‐b‐PAA(3700), respectively. Polymeric micelles are formed by self‐assembly once dactolisib is conjugated via the ethylenediamine platinum(II) linker (Lx) to the PAA block of the block copolymers. Dactolisib micelles with dactolisib loading content of 17% w/w show good colloidal stability and display sustained release of Lx‐dactolisib over 96 h in PBS at 37 °C, while media containing reagents that compete for platinum coordination (e.g., glutathione (GSH) or dithiothreitol (DTT)) effectuate release of the parent inhibitor dactolisib at similar release rates. Dactolisib/lissamine‐loaded micelles are internalized by human breast adenocarcinoma cells (MCF‐7) in a dose and time‐dependent manner as demonstrated by confocal microscopy. Dactolisib‐loaded micelles inhibit the PI3K/mTOR signaling pathway at low concentrations (400 × 10^?9 m ) and exhibit potent cytotoxicity against MCF‐7 cells with IC₅₀ values of 462 ± 46 and 755 ± 75 × 10^?9 m for micelles with either short or longer PEG‐b‐PAA block lengths. In conclusion, dactolisib loaded PEG‐b‐PAA micelles are successfully prepared and hold potential for nanomedicine‐based tumor delivery of dactolisib.     

Luminescent properties of PEG-added nanocrystalline YVO4:Eu phosphor prepared by a hydrothermal method

In an effort to obtain enhanced luminescence under photoexcitation as well as to clarify the underlying correlation between non-radiative sites and a surface modifier in a nanoscale phosphor, YVO₄:Eu³⁺ was synthesized via a polyethylene glycol (PEG)-assisted hydrothermal process. The temperature variable photoluminescence reveals that the overall emission behaviors of PEG-added YVO₄:Eu³⁺ phosphor was similar to those of a post-annealed sample without PEG addition. This polymeric agent induces a rough thin layer onto the YVO₄:Eu³⁺ nanoparticle during synthetic procedure, resulting in the prevention of surface-adsorbed species known as non-radiative sites such as NH₄⁺ as well as hydroxyl groups.     

Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL<Superscript>®</Superscript> and <Superscript>90</Superscript>Y-Lactosome for orthotopic mammary tumor

Polymeric micelles (Lactosome) in the size of 20–30 nm were labeled with radionuclides of ¹¹¹In (¹¹¹In-DOTA-Lactosome) for SPECT imaging and ⁹⁰Y (⁹⁰Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of ¹¹¹In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of ⁹⁰Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of ⁹⁰Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of ⁹⁰Y-DOTA-Lactosome and DOXIL^® inhibited the tumor growth during 15 days with their administrations.     

Shell‐isolated nanoparticle enhanced Raman spectroscopy (SHINERS) investigation of benzotriazole film formation on Cu(100), Cu(111), and Cu(poly)

Benzotriazole (BTAH) is well known as an effective corrosion inhibitor for Cu because of its ability to make a coordination polymer film on the surface that provides a barrier to Cu oxidation. BTA⁻ film formation was investigated on single‐crystal and polycrystalline Cu surfaces with shell‐isolated nanoparticle enhanced Raman spectroscopy (SHINERS) using silica‐encapsulated Au nanoparticles. Potential‐dependent spectra display reversible film formation on polycrystalline Cu and irreversible film formation on single‐crystal Cu. Grain boundaries leading to smaller BTA⁻‐Cu oligomers are proposed to be the reason for cathodic degradation of the BTA⁻ polymeric films on polycrystalline Cu. Copyright © 2011 John Wiley & Sons, Ltd.     

Core–Shell Bi2Se3@mSiO2‐PEG as a Multifunctional Drug‐Delivery Nanoplatform for Synergistic Thermo‐Chemotherapy with Infrared Thermal Imaging of Cancer Cells

Thermo‐chemotherapy combining photothermal therapy (PTT) with chemotherapy has become a potent approach for antitumor treatment. In this study, a multifunctional drug‐delivery nanoplatform based on polyethylene glycol (PEG)‐modified mesoporous silica‐coated bismuth selenide nanoparticles (referred to as Bi₂Se₃@mSiO₂‐PEG NPs) is developed for synergistic PTT and chemotherapy with infrared thermal (IRT) imaging of cancer cells. The product shows no/low cytotoxicity, strong near‐infrared (NIR) optical absorption, high photothermal conversion capacity, and stability. Utilizing the prominent photothermal effect, high‐contrast IRT imaging and efficient photothermal killing effect on cancer cells are achieved upon NIR laser irradiation. Moreover, the successful mesoporous silica coating of the Bi₂Se₃@mSiO₂‐PEG NPs cannot only largely improve the stability but also endow the NPs high drug loading capacity. As a proof‐of‐concept model, doxorubicin (DOX) is successfully loaded into the NPs with rather high loading capacity (≈50.0%) via the nanoprecipitation method. It is found that the DOX‐loaded NPs exhibit a bimodal on‐demand pH‐ and NIR‐responsive drug release property, and can realize effective intracellular drug delivery for chemotherapy. The synergistic thermo‐chemotherapy results in a significantly higher antitumor efficacy than either PTT or chemotherapy alone. The work reveals the great potential of such core–shell NPs as a multifunctional drug‐delivery nanosystem for thermo‐chemotherapy.     

Polyacrylamide Nanoparticles with Visible and Near‐Infrared Autofluorescence

Nowadays, self‐fluorescent materials such as quantum dots are widely studied and applied in biomedical field. However, the biggest obstacle is biocompatibility. Here, a novel autofluorescent nanoparticle is constructed by crosslinking polyacrylamide nanoparticles (PAANPs) that contain ε‐poly‐l ‐lysine with glutaraldehyde (named fPAANPs). The nanoparticle has a mean size of about 16 nm, a zeta potential of about +16 mV, and strong visible and near‐infrared autofluorescence. The nanoparticle can be efficiently internalized into cells with high biocompatibility, the LC50 of which in RAW264.7, HepG2, and Hepa1‐6 cells is 6, 9, and 7.5 mg mL^?1, respectively. The nanoparticle shows no visible impact on the mice vitality even at a high intravenously administered dose (126 mg kg^?1). The autofluorescence of fPAANPs shows high stability, persistence, allowing long‐term dynamic imaging for 25 d in subcutaneous injections and 18 d in xenograft tumors in mice. The nanoparticle thus provides a self‐traceable nanomaterial that can be exploited as drug carrier and potential photodynamic therapy photosensitizer.     

Synthesis of biocompatible uniform NaYF4:Yb3+,Er3+ nanocrystals and their characteristic photoluminescence

For biological application, lanthanide ion doped upconverting nanocrystals should be modified to be biocompatible. Here, we show a viable and efficient procedure for producing biocompatible NaYF₄:Yb³⁺,Er³⁺ upconverting nanocrystals. The uniform NaYF₄:Yb,Er upconverting nanocrystals were firstly synthesized by a mild chemical procedure, which were subsequently coated with a layer of polyethylene-glycol (PEG) to be biocompatible. The photoluminescent intensity of the PEG coated NaYF₄:Yb,Er nanocrystals varies nonlinearly with increasing the thickness of the PEG coating. In particular, it was noted that the Intensity Ratio of Red to Green Emission (IRRGE) of PEG coated NaYF₄:Yb,Er was highly depended on the excitation power density: IRRGE keeping almost constant with increasing the excitation power density below 826 W/cm², but remarkably increasing when increasing the excitation power density above 826 W/cm². For this unique phenomenon, the excitation and emission mechanisms related to PEG coating were discussed.     

Polymerization of 2‐(hydroxyethyl)methacrylate by two different initiator/accelerator systems: a Raman spectroscopic monitoring

The control of monomer polymerization is important when preparing biocompatible devices. The compound 2‐(hydroxyethyl)methacrylate can be polymerized by redox systems using benzoyl peroxide (BPO) (as accelerator) and a substituted amine (as initiator). However, this system is associated with a highly exothermic polymerization, and end‐products with inflammatory properties are produced. We have used ascorbic acid (AA) to induce BPO fragmentation and have compared the kinetics of the reaction, by Raman microscopy, with that obtained with a substituted amine. The breaking of the C bond (Raman stretching vibration at 1641 cm⁻¹) could be monitored in both cases and reflected the incorporation of new monomer molecules into the chain. The AA‐induced polymerization was slower than with the substituted amine and was accompanied by the appearance of a new band at 1603 cm⁻¹, assigned to the stretching vibrations of  COOH species incorporated into the chains. Raman microscopy appears to be a powerful tool in the study of polymeric biomaterial preparation. Copyright © 2008 John Wiley & Sons, Ltd.     

Multifunctional Plasmonic Co‐Doped Fe2O3@polydopamine‐Au for Adsorption,Photocatalysis, and SERS‐based Sensing

A new type of multifunctional plasmonic nanoparticles, cobalt‐doped Fe₂O₃@polydopamine‐Au (Co‐Fe₂O₃@PDA‐Au), is fabricated via coating PDA through self‐polymerization onto Co‐Fe₂O₃ and further loading gold nanoparticles by in situ reduction onto the surface of PDA shell. Benefiting from the universal adhesive ability of PDA and negative zeta potetntial of the composite, the Co‐Fe₂O₃@PDA‐Au shows strong adsorptivity for cationic dyes. The presence of gold nanoparticle with the diameter of 15 nm in the Co‐Fe₂O₃@PDA‐Au system promotes surface‐enhanced Raman scattering (SERS) activity with an impressive detection limit of 1 × 10^?6 m . Thanks to the synergistic effect of the light harvesting of PDA, the surface plasmon resonance of Au, and the electron conductibility of PDA and Au, the Co‐Fe₂O₃@PDA‐Au exhibits an enhanced photocatalytic activity comparing with unmodified Co‐Fe₂O₃. All the above‐mentioned functions enable Co‐Fe₂O₃@PDA‐Au to be a multifunctional material system for various applications toward environmental pollutants.     

Laser synthesis of aluminium nanoparticles in biocompatible polymer solutions

Pulsed laser ablation of Aluminium (Al) in pure water rapidly forms a thin alumina (Al₂O₃) layer which drastically modifies surface plasmon resonance (SPR) absorption characteristics in deep-UV region. Initially, pure aluminium nanoparticles (NPs) are generated in water without any stabilizers or surfactants at low laser fluence which gradually transform to stable Al-Al₂O₃ core-shell nanostructure with increasing either residency time or fluence. The role of laser wavelength and fluence on the SPR properties and oxidation characteristics of Al NPs has been investigated in detail. We also present a one-step in situ synthesis of oxide-free stable Al NPs in biocompatible polymer solutions using laser ablation in liquid method. We have used nonionic polymers (PVP, PVA and PEG) and anionic surfactant (SDS) stabilizer to suppress the Al₂O₃ formation and studied the effect of polymer functional group, polymeric chain length, polymer concentration and anionic surfactant on the incipient embryonic aluminium particles and their sizes. The different functional groups of polymers resulted in different oxidation states of Al. PVP and PVA polymers resulted in pure Al NPs; however, PEG and SDS resulted in alumina-modified Al NPs. The Al nanoparticles capped with PVP, PVA, and PEG show a good correlation between nanoparticle stability and monomeric length of the polymer chain.     

Facile Synthesis of Lactobionic Acid‐Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)‐targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)‐stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol‐LA (LA‐PEG‐COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA‐targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA‐targeted Fe₃O₄ NPs are colloidally stable and water‐dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10^?3 m ^?1 s^?1) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA‐targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine‐mediated conjugation chemistry, a range of different Fe₃O₄ NP‐based nanoprobes may be developed for theranostics of different types of cancer.     

Nano‐opto‐mechanical effects in plasmonic waveguides

In order to achieve interaction between light beams, a mediating material object is required. Nonlinear materials are commonly used for this purpose. Here a new approach to control light with light, based on a nano‐opto‐mechanical system integrated in a plasmonic waveguide is proposed. Optomechanics of a free‐floating resonant nanoparticle in a subwavelength plasmonic V‐groove waveguide is studied. It is shown that nanoparticle auto‐oscillations in the waveguide induced by a control light result in the periodic modulation of a transmitted plasmonic signal. The modulation depth of 10% per single nanoparticle of 25 nm diameter with the clock frequencies of tens of MHz and the record low energy‐per‐bit energies of 10⁻¹⁸ J is observed. The frequency of auto‐oscillations depends on the intensity of the continuous control light. The efficient modulation and deep‐subwavelength dimensions make this nano‐optomechanical system of significant interest for opto‐electronic and opto‐fluidic technologies.     

Cell Membrane-Coated AuNPs as a New Biomimetic Platform for ROS Scavenger Provides Cytoprotection from Apoptosis Induced by Oxidative Stress

Biocompatible nanoparticles have attracted considerable attention as cellular antioxidant agents for the improvement of new therapeutics for several and diverse oxidative stress related disorders. Here, it is shown that the biocompatible cell membrane@gold nanoparticle displays catalase-mimic behavior by decomposing H₂O₂. This interesting behavior can be used for cell protection against induced oxidative injury by reactive oxygen species (ROS). So, after characterizing this novel biocompatible nanostructure, the protective effect of cell membrane@AuNPs pretreatment in front of a well-defined oxidative stress-inducing chemotherapy drug, doxorubicin (Dox) is assessed. Doxorubicin pretreatment significantly reduces the intracellular ROS production. Similarly, a reduction in the levels of DNA oxidative damage, as measured with the AO/EB staining, is also observed. Obtained results would support that this novel nanostructure can show how a pharmacological agent can be used against oxidative stress-mediated diseases.     

Structural role of polyethylene glycol in the formation of anatase nanocrystalline titania at low temperature

Anatase nanocrystalline TiO₂ thin films were obtained by a sol–gel dip‐coating method, in which the nanocrystallization is effected by a simple hot water treatment of the deposited films at temperatures below 90 °C under atmospheric pressure for 1 h. The dip‐coating sol was prepared by reacting titanium tetra‐n‐butoxide [Ti(OⁿBu)₄] with polyethylene glycol (PEG) in ethanol. Films obtained from a sol that do not contain PEG show no sign of crystallization, demonstrating the importance of PEG in the crystallization process. Raman studies of reaction dynamics show that PEG undergoes a nucleophilic substitution reaction replacing butoxy groups in Ti(OⁿBu)₄. Stoichiometric reactions of Ti(OⁿBu)₄ with PEG in polar and nonpolar solvents were performed, and they yielded different titanium–PEG hybrid polymers, which were isolated and characterized by various spectroscopic techniques such as IR, Raman, solid‐state NMR and MALDI‐TOF‐MS. NMR studies evidenced the location and the way in which PEG is bonded with titanium atoms in the titanium–PEG hybrid polymers. On the basis of these studies, we have proposed structures for these polymers. It is demonstrated that the structure of the obtained polymers plays an important role in the formation of anatase TiO₂ nanoparticles in hot water at temperatures below 90 °C under atmospheric pressure. Copyright © 2009 John Wiley & Sons, Ltd.