Dual‐Mode Antibacterial Conjugated Polymer Nanoparticles for Photothermal and Photodynamic Therapy

In this work, dual‐mode antibacterial conjugated polymer nanoparticles (DMCPNs) combined with photothermal therapy (PTT) and photodynamic therapy (PDT) are designed and explored for efficient killing of ampicillin‐resistant Escherichia coli (Amp^r E. coli). The DMCPNs are self‐assembled into nanoparticles with a size of 50.4 ± 0.6 nm by co‐precipitation method using the photothermal agent poly(diketopyrrolopyrrole‐thienothiophene) (PDPPTT) and the photosensitizer poly[2‐methoxy‐5‐((2‐ethylhexyl)oxy)‐p‐phenylenevinylene] (MEH‐PPV) in the presence of poly(styrene‐co‐maleic anhydride) which makes nanoparticles disperse well in water via hydrophobic interactions. Thus, DMCPNs simultaneously possess photothermal effect and the ability of sensitizing oxygen in the surrounding to generate reactive oxygen species upon the illumination of light, which could easily damage resistant bacteria. Under combined irradiation of near‐infrared light (550 mW cm^?2, 5 min) and white light (65 mW cm^?2, 5 min), DMCPNs with a concentration of 9.6 × 10^?4 µm could reach a 93% inhibition rate against Amp^r E. coli, which is higher than the efficiency treated by PTT or PDT alone. The dual‐mode nanoparticles provide potential for treating pathogenic infections induced by resistant microorganisms in clinic.     

Phosphorescent Polymeric Nanoparticles by Coordination Cross‐Linking as a Platform for Luminescence Imaging and Photodynamic Therapy

Water‐soluble phosphorescent polymeric nanoparticles with an average diameter of approximately 100 nm were synthesized by a coordination cross‐linking reaction. The pyridine blocks in poly(4‐vinyl pyridine‐b‐ethylene oxide) (P4VP‐b‐PEO) were cross‐linked by the iridium chloride‐bridged dimer in DMF solution. Owing to the presence of an iridium complex with different ligands in the core of the polymeric nanoparticles, NP‐1, NP‐2, and NP‐3 showed bright green, yellow, and red phosphorescence, respectively. PEG chains in the shell gave the polymeric nanoparticles solubility and biocompatibility, which was confirmed by an MTT assay using HeLa cells as a model cancer cell line. The flow cytometry and laser confocal fluorescence microscopy results revealed NP‐2, as an example, could be effectively uptaken by HeLa cells. Therefore, these polymeric nanoparticles can be used as luminescent probes for living cells. In addition, ¹O₂ could be effectively generated in the presence of NP‐2 upon irradiation with visible light (λ>400 nm, 300 mW cm^?2), which was confirmed by a clear decrease in the fluorescence intensity of 9,10‐dimethylanthracene (DMA). After incubation with NP‐2 at a concentration of 200 μg mL^?1 for 6 h, approximately 90 % of HeLa cells were effectively ablated upon irradiation with visible light for only 10 min, indicating the potential for photodynamic therapy with polymeric nanoparticles.     

Harvesting Light To Produce Heat: Photothermal Nanoparticles for Technological Applications and Biomedical Devices

The photothermal properties of nanoparticles (NPs), that is, their ability to convert absorbed light into heat, have been studied since the end of the last century, mainly on gold NPs. In the new millennium, these studies have developed into a burst of research dedicated to the photothermal ablation of tumors. However, beside this strictly medical theme, research has also flourished in the connected areas of photothermal antibacterial surface coatings, gels and polymers, of photothermal surfaces for cell stimulation, as well as in purely technological areas that do not involve medical biotechnology. These include the direct conversion of solar light into heat, a more efficient sun-powered generation of steam and the use of inkjet-printed patterns of photothermal NPs for anticounterfeit printing based on temperature reading, to cite but a few. After an analysis of the photothermal effect (PTE) and its mechanism, this minireview briefly considers the antitumor-therapy theme and takes an in-depth look at all the other technological and biomedical applications of the PTE, paying particular attention to photothermal materials whose NPs have joined those based on Au.     

Near Infrared Dye Conjugated Nanogels for Combined Photodynamic and Photothermal Therapies

There is a need for new and smart formulations that will help overcome the limitations of organic dyes used in photodynamic (PDT) and photothermal (PTT) therapy and significantly accelerate their clinical translation. Therefore the aim of this work was to create a responsive nanogel scaffold as a smart vehicle for dye administration. We developed a methodology that enables the conjugation of organic dyes to thermoresponsive nanogels and yields biocompatible, nanometer‐sized products with low polydispersity. The potential of the dye‐nanogel conjugate as a photothermal and photodynamic agent has been demonstrated by an in vitro evaluation with a model human carcinoma cell line. Additionally, confocal cell images showed their cellular uptake profile and their potential for bioimaging and intracellular drug delivery. These conjugates are a promising scaffold as a theranostic agents and will enable further applications in combination with controlled drug release.

     

Semiconducting Polycomplex Nanoparticles for Photothermal Ferrotherapy of Cancer

This study reports the development of iron‐chelated semiconducting polycomplex nanoparticles (SPFeN) for photoacoustic (PA) imaging‐guided photothermal ferrotherapy of cancer. The hybrid polymeric nanoagent comprises a ferroptosis initiator (Fe³⁺) and an amphiphilic semiconducting polycomplex (SP_C) serving as both the photothermal nanotransducer and iron ion chelator. By virtue of poly(ethylene glycol) (PEG) grafting and its small size, SPFeN accumulates in the tumor of living mice after systemic administration, which can be monitored by PA imaging. In the acidic tumor microenvironment, SPFeN generates hydroxyl radicals, leading to ferroptosis; meanwhile, under NIR laser irradiation, it generates localized heat to not only accelerate the Fenton reaction but also implement photothermal therapy. Such a combined photothermal ferrotherapeutic effect of SPFeN leads to minimized dosage of iron compared to previous studies and effectively inhibits the tumor growth in living mice, which is not possible for the controls.     

以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究进展

光动力疗法作为一种非侵入性治疗手段已广泛应用于肿瘤的临床治疗。然而其疗效却深受紫外-可见光组织穿透深度的限制。镧系掺杂上转换纳米颗粒可以将近红外光转换为紫外-可见光,被广泛用于与传统光敏剂结合实现更为高效的光动力治疗。近年来,以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究备受关注,本文重点介绍了该领域的最新研究进展,并对其未来发展方向作出了展望。     

含碘二氧化硅纳米颗粒对BODIPY染料光动力效果的影响

利用含碘硅烷前体制备包裹BODIPY染料分子的纳米二氧化硅颗粒.颗粒中的碘原子通过重原子效应有效提高了BODIPY染料分子的系间窜越效率,进而提高了染料分子的单重态氧量子产率及光损伤DNA的能力.这一结果表明,含碘二氧化硅纳米颗粒可以成为众多荧光染料分子在光动力疗法领域应用的一个有效药物负载和输送体系.     

Rapid Colorimetric Identification and Targeted Photothermal Lysis of Salmonella Bacteria by Using Bioconjugated Oval‐Shaped Gold Nanoparticles

Salmonella bacteria are the major cause for the infection of 16 million people worldwide with typhoid fever each year. Antibiotic‐resistant Salmonella strains have been isolated from various food products. As a result, the development of ultrasensitive sensing technology for detection and new approaches for the treatment of infectious bacterial pathogens that do not rely on traditional therapeutic regimes is very urgent for public health, food safety, and the world economy. Driven by this need, we report herein a nanotechnology‐driven approach that uses antibody‐conjugated oval‐shaped gold nanoparticles to selectively target and destroy pathogenic bacteria. Our experiments have shown the use of a simple colorimetric assay, with an anti‐salmonella antibody conjugated to oval‐shaped gold nanoparticles, for the label‐free detection of S. typhimurium with an excellent detection limit (10⁴ bacteria per mL) and high selectivity over other pathogens. When bacteria conjugated to oval‐shaped gold nanoparticles were exposed to near‐infrared radiation, a highly significant reduction in bacterial cell viability was observed due to photothermal lysis. Ideally, this nanotechnology‐based assay would have enormous potential for rapid, on‐site pathogen detection to avoid the distribution of contaminated foods.     

Assembly of Fe2O3 Nanoparticles with Polymer Microspheres by Encapsulated Copolymerization

Inorganic nanoparticles Fe₂O₃ in diameter of 3-5 nm have been assembled with polymer microspherer and then encapsulated in copolymer of St/BA/AA by polymerization process. Fe₂O₃ encapsulated microspheres can obtained through interaction between surface groups of the two component particles and by adjusting the pH value in the emulsion. Pre-treatment of the composite particles using a certain amount of surfactant before polymerization can give a good encapsulation.     

纳米银形状控制合成与聚合物纳米银复合材料

纳米银(Ag NPs)由于其独特的物理、化学和生物学特性备受研究人员的关注.纳米银应用性能除了受到粒子尺寸、分布、纯度等因素影响,还与纳米银的形状密切相关.纳米银的形状对纳米银的抗菌性能、光学性能以及聚合物纳米银复合材料的综合性能都会产生重要影响.纳米银的形状控制合成可以进一步发挥聚合物纳米银复合材料的性能潜力.因此,不断发展纳米银新的合成方法,研究纳米银形状控制的机理就显得尤为重要.本文综述了纳米银合成方法和不同形状纳米银的最新研究进展,合成方法重点介绍了辐射法、激光烧蚀法、电化学法、光化学法和生物合成法,评述了这些方法的优缺点;同时从模板法、动力学、热力学以及氧化刻蚀4个方面介绍了纳米银形状控制的机理.介绍了聚合物纳米银复合材料的研究进展.     

Controlled Alternating Copolymerization of (Meth)acrylates and Vinyl Ethers by Using Organoheteroatom‐Mediated Living Radical Polymerization

Alternating copolymers comprised of (meth)acrylates and vinyl ethers with controlled molecular weights and polydispersities were synthesized for the first time by living radical polymerization using organotellurium, stibine, and bismuthine chain transfer agents. Combining living alternating copolymerization and living radical or living cationic polymerization afforded hitherto unavailable block copolymers with controlled macromolecular structures.

     

模板聚合法制备高浓度PMAA/HEC核-壳聚合物纳米微球

以羟乙基纤维素(HEC)为大分子模板,选用甲基丙烯酸(MAA)单体,通过模板聚合一步反应,制备了较高浓度(40 mg/mL)的核-壳结构聚合物纳米微球溶液。采用透射电镜、红外光谱、粒径-电位和荧光光谱等分析方法,研究了PMAA/HEC纳米微球的形态、结构、原位形成机理和pH响应特性。结果表明:在大分子间氢键作用的驱动下,原位生成的PMAA和HEC自组装形成了以不溶性的PMAA/HEC大分子复合物为核、以可溶性HEC为壳的PMAA/HEC聚合物纳米微球。微球在pH=0.7~4.0范围内表现出较明显的pH敏感性。     

Self-assembly of Amphiphilic Porphyrins To Construct Nanoparticles for Highly Efficient Photodynamic Therapy

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP−PPh₃, TPP−PPh₃−2PEG and TPP−PPh₃−4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP−PPh₃−4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.     

Strategy for Tuning the Photophysical Properties of Photosensitizers for Use in Photodynamic Therapy

A novel approach for tuning spectral properties, as well as minimizing aggregation, in zinc porphyrin and zinc phthalocyanine‐based compounds is presented. Particular emphasis is placed on use of these compounds as photosensitizers in photodynamic therapy (PDT). To accomplish this aim, a bulky hydrophobic cation, trihexyltetradecylphosphonium, is paired with anionic porphyrin and phthalocyanine dyes to produce a group of uniform materials based on organic salts (GUMBOS) that absorb at longer wavelengths with high molar absorptivity and high photostability. Nanoparticles derived from these GUMBOS possess positively charged surfaces with high zeta potential values, which are highly desirable for PDT. Upon irradiation at longer wavelengths, these GUMBOS produced singlet oxygen with greater efficiency as compared to the respective parent dyes.     

Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy

A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation.     

Gold Nanorod–Photosensitizer Complex Obtained by Layer‐by‐Layer Method for Photodynamic/Photothermal Therapy In Vitro

Gold nanorod (GNR)–photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin‐18) and cationic poly(allylamine hydrochloride) by layer‐by‐layer method, and was characterized by transmission electron microscopy, UV‐vis spectroscopy, and zeta potential. The GNR–PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT.