Near‐Infrared‐Activated Nanocalorifiers in Microcapsules: Vapor Bubble Generation for In Vivo Enhanced Cancer Therapy

Photothermal therapy based on gold nanostructures has been widely investigated as a state‐of‐the‐art noninvasive therapy approach. Because single nanoparticles cannot harvest sufficient energy, self‐assemblies of small plasmonic particles into large aggregates are required for enhanced photothermal performance. Self‐assembled gold nanorods in lipid bilayer‐modified microcapsules are shown to localize at tumor sites, generate vapor bubbles under near‐infrared light exposure, and subsequently damage tumor tissues. The polyelectrolyte multilayer enables dense packing of gold nanorods during the assembly process, which leads to the formation of vapor bubbles around the excited capsules. The resulting vapor bubbles achieve a high efficiency of suppressing tumor growth compared to single gold nanorods. In vivo experiments demonstrated the ability of soft‐polymer multilayer microcapsules to cross the biological barriers of the body and localize at target tissues.     

Design of a Cellular‐Uptake‐Shielding Magnetic Catcher for Cancer Cell Separation

Fluorescent‐magnetic‐biotargeting multifunctional microcapsules (FMBMMs) are designed and fabricated via layer‐by‐layer assembly. It is found that the arginine‐glycine‐aspartate‐modified FMBMMs were capable of sensitively detecting and efficiently isolating approximately 80% target cancer cells within 20 min. More importantly, FMBMMs present a general template for identifying and separating multiple types of cancer cells simply by altering the recognition motif.

     

Fast Self‐Healing of Polyelectrolyte Multilayer Nanocoating and Restoration of Super Oxygen Barrier

A self‐healable gas barrier nanocoating, which is fabricated by alternate deposition of polyethyleneimine (PEI) and polyacrylic acid (PAA) polyelectrolytes, is demonstrated in this study. This multilayer film, with high elastic modulus, high glass transition temperature, and small free volume, has been shown to be a super oxygen gas barrier. An 8‐bilayer PEI/PAA multilayer assembly (≈700 nm thick) exhibits an oxygen transmission rate (OTR) undetectable to commercial instrumentation (<0.005 cc (m⁻² d⁻¹ atm⁻¹)). The barrier property of PEI/PAA nanocoating is lost after a moderate amount of stretching due to its rigidity, which is then completely restored after high humidity exposure, therefore achieving a healing efficiency of 100%. The OTR of the multilayer nanocoating remains below the detection limit after ten stretching‐healing cycles, which proves this healing process to be highly robust. The high oxygen barrier and self‐healing behavior of this polymer multilayer nanocoating makes it ideal for packaging (food, electronics, and pharmaceutical) and gas separation applications.

     

Layer—by—layer Multilaryer Films Self—assembled from a Rare—earth—containing Poly—oxometalate,Na9[Eu（W5O18）2] and Poly （allylamine hydrochloride） and Their Photoluminescent Properties

Ultrathin multilayer films of a rare-earth-containing polyoxometalate Na9[Eu(W5O18)2](EW) and poly (allymamine hydrochloride)(PAH) have been prepared by layer-by-layer self-assembly from dilute aqueous solution.The fabrication process of the EW/PAH multilaryer films was followed by UV-vis spectroscopy and ellipsometry,which show that the deposition process is linear and highly reproducible from layer to layer.An average EW/PAH bilayer thickness of ca.2.1nm was determined by ellipsometry.In addition,the scanning electron microscopy(SEM) image of the EW/PAH film indicates that the film surface is relatively uniform and smooth.The photoluminescent properties of these films were also investigated by fluorescence spectroscopy.     

Therapeutic Efficacy of 2‐Methoxyestradiol Microcrystals Encapsulated within Polyelectrolyte Multilayers

Development of a novel formulation of anticancer drugs to improve their water‐solubility and bioavailability remains a great challenge. Herein, the potential anticancer agent 2‐methoxyestradiol (2‐ME) was selected as a model drug and was encapsulated within polyelectrolyte (PE) multilayers by layer‐by‐layer deposition of oppositely charged PEs onto the drug microcrystal surfaces. Cell viability and morphology observation of two cell lines reveal that the PE multilayer‐encapsulated 2‐ME microcrystals markedly decrease the cell viability, displaying similar inhibitory effect to that of the conventional formulation of 2‐ME dissolved in ethanol. The current approach to encapsulate hydrophobic drug microparticles may be useful for formulating different drugs for a variety of biological applications.

     

Washless Method Enables Multilayer Coating of an Aggregation‐Prone Nanoparticulate Drug Delivery System with Enhanced Yields,Colloidal Stability,and Scalability

Aggregation is frequently encountered during coating nanoparticles, especially when the core is not solid and the coating polyelectrolytes are weak. Here, the coating of a nanoliposome with two weak polyelectrolytes, alginate and chitosan, is investigated. First, quartz crystal microbalance with dissipation, atomic force microscopy, scanning electron microscopy, and energy dispersive spectroscopy analyses confirm the feasibility of firm adsorption of up to 16 layers of weak polyelectrolytes to the liposomal surface. Titrations are then performed to identify the lowest amounts of polyelectrolytes required to make eight saturated coating layers using the washless method. Significantly improved yields and reproducibility (almost 100%) are achieved, in addition to control over layer thickness. Attenuated total reflectance Fourier transform infrared spectroscopy studies confirm the success of layering. This is special since scientists always attempt to reduce nanoparticle aggregation by substituting the soft core, using one strong polyelectrolyte, or contending with lower yields or numbers of coating layers.

     

Semiconducting Polymer Nanoenzymes with Photothermic Activity for Enhanced Cancer Therapy

Regulation of enzyme activity is fundamentally challenging but practically meaningful for biology and medicine. However, noninvasive remote control of enzyme activity in living systems has been rarely demonstrated and exploited for therapy. Herein, we synthesize a semiconducting polymer nanoenzyme with photothermic activity for enhanced cancer therapy. Upon near‐infrared (NIR) light irradiation, the activity of the nanoenzyme can be enhanced by 3.5‐fold to efficiently digest collagen in the tumor extracellular matrix (ECM), leading to enhanced nanoparticle accumulation in tumors and consequently improved photothermal therapy (PTT). This study thus provides a promising strategy to remotely regulate enzyme activity for cancer therapy.     

Influence of Side‐Chain Composition on Polythiophene Properties and Supramolecular Assembly of Anionic Polythiophene Derivatives

A series of 10 polythiophene derivatives is reported, in which each polymer has a different percentage of carboxylic acid‐bearing repeat units. The properties of these polymers are explored under acidic conditions, where the carboxylic acid moieties remain neutral, and under basic conditions, where the carboxylic acid units become anionic carboxylates. The properties that are examined for both solutions and films include UV–vis absorption spectroscopy, photoluminescence spectroscopy, and red‐edge optical band gaps. All the properties studied are strongly dependent both on protonation state and percentage of carboxylic acid/carboxylate side chains along the polymer backbone. The anionic form of each polythiophene derivative was also used in layer‐by‐layer film deposition with a cationic phosphonium polyelectrolyte. The film growth process was studied by spectroscopic techniques to assess the influence of side‐chain composition on the film growth and optical properties. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019     

Encapsulation of Photosensitizer into Multilayer Microcapsules by Combination of Spontaneous Deposition and Heat‐Induced Shrinkage for Photodynamic Therapy

Annealing of PDADMAC/PSS multilayer microcapsules assembled on PSS‐doped CaCO₃ particles at 80 °C for 30 min reduces their size dramatically from 6.9 ± 0.3 to 3.1 ± 0.5 µm. Methylene blue molecules are encapsulated by spontaneous deposition and post‐annealing with a concentration of 22 mg · mL^?1, which is 1000 times higher than the feeding value. The unreleased MB molecules are retained stably for a long time, which are then protected by the capsules against reductive enzymes and keep their photodynamic activity. The viability of HeLa cells incubated with the MB‐loaded capsules decreases sharply from ≈75 (dark cytotoxicity) to ≈20% after irradiation with a laser at 671 nm and 60 J · cm^?2 for 75 s.

     

Low Band Gap Donor‐Acceptor Conjugated Polymer Nanoparticles and their NIR‐mediated Thermal Ablation of Cancer Cells

Low band gap D‐A conjugated PNs consisting of 2‐ethylhexyl cyclopentadithiophene co‐polymerized with 2,1,3‐benzothiadiazole (for nano‐PCPDTBT) or 2,1,3‐benzoselenadiazole (for nano‐PCPDTBSe) have been developed. The PNs are stable in aqueous media and showed no significant toxicity up to 1 mg · mL^?1. Upon exposure to 808 nm light, the PNs generated temperatures above 50 °C. Photothermal ablation studies of the PNs with RKO and HCT116 colorectal cancer cells were performed. At concentrations above 100 µg · mL^?1 for nano‐PCPDTBSe, cell viability was less than 20%, while at concentrations above 62 µg · mL^?1 for nano‐PCPDTBT, cell viability was less than 10%. The results of this work demonstrate that low band gap D‐A conjugated polymers 1) can be formed into nanoparticles that are stable in aqueous media; 2) are non‐toxic until stimulated by IR light and 3) have a high photothermal efficiency.

     

Individually Addressable Patterned Multilayer Microchambers for Site‐Specific Release‐On‐Demand

Patterned arrays of light‐responsive microchambers are suggested as candidates for site‐specific release of chemicals in small and precisely defined quantities on demand. A composite film is made of poly(allylammonium)‐poly(styrene sulfonate) multilayers and gold nanoparticles incorporated between subsequent stacks of polyelectrolytes. The film shaped as microchambers is loaded with colloid particles or oil‐soluble molecules. The microchambers are sealed onto a glass slide precoated with an adhesive poly(diallyldimethylammonium)‐poly(styrene sulfonate) multilayer film. A focused laser beam is used for remote addressing the individual microchambers and site‐specific release of the loaded cargo.     

Reversible pH‐Dependent Properties of Multilayer Microcapsules Made of Weak Polyelectrolytes

Summary: We investigated microcapsules composed of the weak polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) assembled on calcium carbonate cores. These capsules are stable in the pH range from 2.5 to 11.5, undergoing reversible swelling in the pH interval from 2.7 to 2.6. Capsule swelling occurs at a protonation degree above 90%. The pH‐dependent size variation of PAH/PMA capsules is blocked after crosslinking of the polyelectrolyte layers.

Schematic of the swelling and de‐swelling of the capsules with changing pH.     

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.     

Effective Cancer Cell Killing by Hydrophobic Nanovoid‐Enhanced Cavitation under Safe Low‐Energy Ultrasound

β‐Cyclodextrin (β‐CD)‐capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low‐energy ultrasound (≤1.0 W cm^?2, 1 MHz). The water‐dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low‐energy ultrasound (≤1.0 W cm^?2, 1 MHz). A significant cancer cell killing effect was observed in cancer cells and in a mouse xenograft tumor model treated with the nanoagents together with the low‐energy ultrasound, showing a distinct dependence on the concentration of nanoagents and ultrasound intensity. By contrast, an antitumor effect was not observed when either low‐energy ultrasound or nanoagents were applied alone. These findings are significant as the technique promises a safe, low‐cost, and effective treatment for cancer therapy.     

Facile Fabrication of Near‐Infrared‐Responsive and Chitosan‐Functionalized Cu2Se Nanoparticles for Cancer Photothermal Therapy

Photothermal therapy has attracted much interest for use in cancer treatment in recent years. In this study, Cu₂Se nanoparticles as a novel photothermal agent modified by chitosan (CS‐Cu₂SeNPs) were successfully synthesized through a facile route at room temperature. The as‐synthesized CS‐Cu₂SeNPs exhibited good water solubility and significant stability. CS‐Cu₂SeNPs can efficiently convert near‐infrared (NIR) light into heat and exhibit excellent thermostability. In vitro experiments showed that CS‐Cu₂SeNPs had selective cellular uptake between cancer and normal cells and expressed clear anticancer activity on A375 and HeLa human cancer cells. In addition, the anticancer activity was increased to about 400 % by combination with a laser at 808 nm, which acted through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. CS‐Cu₂SeNPs irradiated with a laser effectively triggered the intracellular reactive oxygen species (ROS) overproduction that promoted cell apoptosis. Therefore, the developed CS‐Cu₂SeNPs could be used as a novel phototherapeutic agent for the photothermal therapy of human cancers.