Fluorescent Polymer Nanoparticles Research Articles

Photoswitchable dual-color fluorescent polymeric nanoparticles for self-erased time-resolved information encryption and anti-counterfeiting

Photoswitchable dual-color fluorescent polymeric nanoparticles for self-erased time-resolved information encryption and anti-counterfeiting

Phenanthroline Derived N-Doped Carbon Dots as Robust Metal-Free Photocatalysts for PET-RAFT Polymerization and Polymerization-Induced Self-Assembly.

Metal-free organic photocatalysts for photo-mediated reversible deactivation radical polymerization (photo-RDRP) are witnessed to make increasing advancement in the precise synthesis of polymers. However, challenges still exist in the development of high-efficiency and environmentally sustainable carbon dots (CDs)-based organocatalysts. Herein, N-doped CDs derived from phenanthroline derivative (Aphen) are prepared as metal-free photocatalysts for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The introduction of phenanthroline structure enhances the excited state lifetime of CDs and expands the conjugated length of their internal structure to enable the light-absorption to reach green light region, thereby enhancing photocatalytic activity. The as-designed CDs exhibit unprecedented photocatalytic capacity in photopolymerization even in large-volume reaction (100mL) with high monomer conversion and narrow polymer dispersity (Mw/Mn < 1.20) under green light. The photocatalytic system is compatible with PET-RAFT polymerization of numerous monomers and the production of high molecular weight polyacrylate (Mn >250000) with exquisite spatiotemporal control. Above results confirm the potential of CDs as photocatalyst, which has not been achieved with other CDs catalysts used in photo-RDRP. In addition, the construction of fluorescent polymer nanoparticles using CDs as both photocatalyst and phosphor through photoinitiated polymerization-induced self-assembly (Photo-PISA) technology is successfully demonstrated for the first time.

Design of chemosensors and dynamic anticounterfeiting inks based on colloidal nanoprecipitated polymers

Fluorescent polymer nanoparticles, prepared by physical incorporation of fluorescein during the nanoprecipitation of the polymers, showed applications in high-level anticounterfeiting and chemical sensing of pH, CO2, and acidic and basic vapors.

Preparation and dynamic color-changing study of fluorescent polymer nanoparticles for individualized and customized anti-counterfeiting application

Preparing new fluorescent materials for individualized and customized anti-counterfeiting applications to meet needs from the rapid development of e-commerce is of great significance. This paper reports the preparation of dynamic color-changing fluorescent polymer nanoparticles (PNPs) by constructing a fluorescence resonance energy transfer (FRET) pair between aggregation-induced emission (AIE) structures and photochromic structures. At first, methyl methacrylate (MMA) was used as the main monomer and tetraphenylethylene (TPE, a typical AIE structure) modified methacrylate (TPE-MA) and photochromic spiropyran (SP) modified methacrylate (SP-MA) as minor monomers were copolymerized to obtain the ternary copolymer PMMA-TPE-SP. Then, two types of PNPs based on this terpolymer was prepared via the reprecipitation method, with and without the addition of an amphiphilic polymer as the surfactant. The photophysical study shows that the fluorescence color of PNPs dynamically changes from blue to light violet and finally to red under UV light irradiation, a process that can be reversed under visible light. The PNPs were alternately irradiated with UV light and visible light for 10 cycles, which proved their good photoswitching reproducibility. The PNPs prepared with addition of surfactant were found to have stronger fluorescence and better stability. Finally, the photochromic fluorescent inks were prepared based on these PNPs. Several anti-counterfeiting scenarios and modes were designed, exhibiting excellent photochromic behavior on cellulose paper, even after 120 days of long-term storage. With simple equipment, desirable anti-counterfeiting effects with dynamic fluorescence color changing was achieved. This study demonstrated a promising hard-to-imitate anti-counterfeiting encryption strategy, which can achieve multiple outputs with simple operation and can be personalized and customized as needed.

Screening Enzymatic Degradation of Polyester Polyurethane with Fluorescent Single-walled Carbon Nanotube and Polymer Nanoparticle Conjugates.

Enzymatic biodegradation is a promising method to reclaim plastic materials. However, to date, a high-throughput method for screening potential enzyme candidates for biodegradation is still lacking. Here, we propose a single-walled carbon nanotube (SWCNT) fluorescence sensor for screening the enzymatic degradation of polyester polyurethane nanoparticles. Through wrapping the SWCNT with cationic chitosan, an electrostatic bond is formed between the SWCNT and Impranil, a widely applied model substrate of polyester polyurethane. As Impranil is being degraded by the enzymes, a characteristic quenching at a short reaction time followed by a brightening at a longer reaction time in the fluorescence signal is observed. The time-dependent fluorescence response is compared with turbidity measurement, and we conclude that the brightening in fluorescence results from the binding of the degradation product with the SWCNT. The proposed SWCNT sensor design has the potential to screen enzyme candidates for selective degradation of other plastic particles.

High-efficiency fluorescent coordination polymer nanoparticles co-doped with Ce3+/Tb3+ ions for curcumin detection.

Curcumin (Cur) possesses diverse biological and pharmacologic effects. It is widely used as a food additive and therapeutic medicine. A study to determine a sensitive detection method for Cur is necessary and meaningful. In this work, double rare earth ions co-doped fluorescent coordination polymer nanoparticles (CPNPs) were developed for the Cur detection. The CPNPs were synthesized by using adenosine monophosphate (AMP) as bridge ligands via coordination self-assembly with Ce3+ and Tb3+. The AMP-Ce/Tb CPNPs exhibited the characteristic green fluorescence of Tb3+ and had high luminescence efficiency. Under the optimal conditions, the fluorescence intensity of AMP-Ce/Tb CPNPs could be significantly quenched by Cur. The fluorescence quenching extent at λex/λem of 300 nm/544 nm showed a good linear relationship with the Cur concentration in the range of 10 to 1000 nM. The detection limit was as low as 8.0 nM (S/N = 3). This method was successfully applied to the determination of Cur in real samples with satisfactory results. The luminescence mechanism of AMP-Ce/Tb CPNPs and the fluorescence quenching mechanism of the CPNPs by Cur were both examined.

Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models.

Real-time guidance through fluorescence imaging improves the surgical outcomes of tumor resections, reducing the chances of leaving positive margins behind. As tumors are heterogeneous, it is imperative to interrogate multiple overexpressed cancer biomarkers with high sensitivity and specificity to improve surgical outcomes. However, for accurate tumor delineation and ratiometric detection of tumor biomarkers, current methods require multiple excitation wavelengths to image multiple biomarkers, which is impractical in a clinical setting. Here, we have developed a biomimetic platform comprising near-infrared fluorescent semiconducting polymer nanoparticles (SPNs) with red blood cell membrane (RBC) coating, capable of targeting two representative cell-surface biomarkers (folate, αυβ3 integrins) using a single excitation wavelength for tumor delineation during surgical interventions. We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking phantoms, and in vivo mouse xenograft tumor models. Favorable biological properties (improved biocompatibility, prolonged blood circulation, reduced liver uptake) are complemented by superior spectral features: (i) specific fluorescence enhancement in tumor regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor biomarkers with single wavelength excitation providing insights about cancer progression (metastases). Our single excitation, dual output approach has the potential to differentiate between the tumor and healthy regions and simultaneously provide a qualitative indicator of cancer progression, thereby guiding surgeons in the operating room with the resection process.

Synthesis of Fluorescent, Small, Stable and Non-Toxic Epitope-Imprinted Polymer Nanoparticles in Water.

Molecularly imprinted polymers (MIPs) are really interesting for nanomedicine. To be suitable for such application, they need to be small, stable in aqueous media and sometimes fluorescent for bioimaging. We report herein, the facile synthesis of fluorescent, small (below 200 nm), water-soluble and water-stable MIP capable of specific and selective recognition of their target epitope (small part of a protein). To synthesize these materials, we used dithiocarbamate-based photoiniferter polymerization in water. The use of a rhodamine-based monomer makes the resulting polymers fluorescent. Isothermal titration calorimetry (ITC) is used to determine the affinity as well as the selectivity of the MIP for its imprinted epitope, according to the significant differences observed when comparing the binding enthalpy of the original epitope with that of other peptides. The toxicity of the nanoparticles is also tested in two breast cancer cell lines to show the possible use of these particle for future in vivo applications. The materials demonstrated a high specificity and selectivity for the imprinted epitope, with a Kd value comparable with the affinity values of antibodies. The synthesized MIP are not toxic, which makes them suitable for nanomedicine.

Biotinylated Fluorescent Polymeric Nanoparticles for Enhanced Immunostaining.

The performance of fluorescence immunostaining is physically limited by the brightness of organic dyes, whereas fluorescence labeling with multiple dyes per antibody can lead to dye self-quenching. The present work reports a methodology of antibody labeling by biotinylated zwitterionic dye-loaded polymeric nanoparticles (NPs). A rationally designed hydrophobic polymer, poly(ethyl methacrylate) bearing charged, zwitterionic and biotin groups (PEMA-ZI-biotin), enables preparation of small (14nm) and bright fluorescent biotinylated NPs loaded with large quantities of cationic rhodamine dye with bulky hydrophobic counterion (fluorinated tetraphenylborate). The biotin exposure at the particle surface is confirmed by Förster resonance energy transfer with dye-streptavidin conjugate. Single-particle microscopy validates specific binding to biotinylated surfaces, with particle brightness 21-fold higher than quantum dot-585 (QD-585) at 550nm excitation. The nanoimmunostaining method, which couples biotinylated antibody (cetuximab) with bright biotinylated zwitterionic NPs through streptavidin, significantly improves fluorescence imaging of target epidermal growth factor receptors (EGFR) on the cell surface compared to a dye-based labeling. Importantly, cetuximab labeled with PEMA-ZI-biotin NPs can differentiate cells with distinct expression levels of EGFR cancer marker. The developed nanoprobes can greatly amplify the signal from labeled antibodies, and thus become a useful tool in the high-sensitivity detection of disease biomarkers.

Ultrarapid Microwave-Assisted Synthesis of Fluorescent Silver Coordination Polymer Nanoparticles and Its Application in Detecting Alkaline Phosphatase Activity

Fluorescent silver coordination polymer nanoparticles (Ag-TPA CPNs) were synthesized using a combination of terephthalic acid (TPA) and silver nitrate via an ultrarapid microwave-assisted strategy within 15 min. The Ag-TPA CPNs displayed a high fluorescent quantum yield (QY = 20.19%) and large Stokes shift (~200 nm), with two emission peaks at 490 nm and 520 nm under an excitation wavelength of 320 nm. A fluorescent "turn-off" method using fluorescent Ag-TPA CPNs was applied to detect the alkaline phosphatase (ALP) activity on the basis of the ALP-catalyzed hydrolysis of ascorbic acid 2-phosphate (AA2P) to ascorbic acid (AA), and the AA product triggered the reduction of Ag+ ions into silver nanoparticles. The fluorescent lifetime of Ag-TPA CPNs decreased from 3.93 ms to 3.80 ms after the addition of ALP, which suggests that this fluorescent "turn-off" detection of ALP activity is a dynamic quenching process. The fluorescent intensity had a linear relationship with the concentration of ALP in the range of 0.2-12 mU/mL (r = 0.991) and with a limit of detection (LOD) of 0.07 mU/mL. It showed high selectivity in ALP detection towards metal ions and amino acids, as well as other enzymes such as horseradish peroxidase, glucose oxidase, tyrosinase, trypsin, lysozyme, and superoxides. When it was applied for the fluorescent "turn-off" detection of ALP activity in serum samples, mean recovery levels ranging from 99.5% to 101.2% were obtained, with relative standard deviations (RSDs) lower than 4% accuracy. Therefore, it is an efficient and accurate tool for analyzing ALP levels in biosamples.

Inhibiting COX-2/PGE2 pathway with biodegradable NIR-Ⅱ fluorescent polymeric nanoparticles for enhanced photodynamic immunotherapy

Photodynamic therapy (PDT) capable of eliciting antitumor immune responses by inducing immunogenic cell death (ICD) holds promise for tumor suppression. However, most photosensitizers suffer from limited degradation, insufficient biocompatibility, and inabilities to generate long-wavelength fluorescence for in vivo tracking. Moreover, PDT has the inherent problem of activating the cyclooxygenase-2/prostaglandin-E2 (COX-2/PGE2) pathway and upregulating programmed cell death ligand 1 (PD-L1) expression, resulting in insufficient efficacy of photodynamic immunotherapy. Herein, we designed and synthesized a dihydroxy-containing BODIPY monomer (MonoBodipy), and then formed the biodegradable polymer (PPDT) by polycondensation reaction, which could generate reactive oxygen species (ROS) for photodynamic immunotherapy and emit near-infrared-Ⅱ (NIR-Ⅱ) fluorescence for bioimaging. Subsequently, we further utilized PPDT to encapsulate the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) to form NPPDT@CXB that could inhibit the COX-2/PGE2 pathway. NPPDT@CXB displayed great anticancer potency on osteosarcoma and ovarian cancer in vitro. Further, NPPDT@CXB could accumulate at tumor site after intravenous administration into tumor-bearing mice, generate ROS, induce ICD cascade, and trigger antitumor immune responses under an 808 nm laser irradiation. The ROS further breaks up thioketal linkages in PPDT, resulting in a rapid CXB release to inhibit the COX-2/PGE2 pathway and then downregulate the PD-L1 expression in tumor cells, which in turn leads to an effective suppression of the primary and distant tumors. This work highlighted a well biocompatible and biodegradable photosensitizer that generates ROS, emits long-wavelength fluorescence, inhibits the COX-2/PGE2 pathway, and downregulates PD-L1 expression simultaneously, exhibiting a robust photodynamic immunotherapy efficacy. This study proposed a new strategy to overcome the inherent problems of photodynamic immunotherapy and pointed out the path of future PDT development.

Polyethyleneimine-based fluorescent polymeric nanoparticles: synthesis and application in fluorescence sensing of pH and para-nitrophenol

Water-soluble polyethyleneimine-based fluorescent polymeric nanoparticles, PEIFPL NPs, were synthesized, characterized and employed for the fluorescence sensing of pH and nitroaromatic compounds.

Thermostably photoswitchable red fluorescent polymeric nanoparticles for rewritable fluorescence patterning and zebrafish imaging

Photoswitchable fluorescent nanomaterials (PFNs) are gaining popularity in a variety of applications including bioimaging, information encryption and anti-counterfeiting. However, the photoswitching properties of traditional PFNs are still far from application, due to the complex background fluorescence interference, the lower brightness and contrast, the poor thermal and light stability. To tackle this question, we developed new thermostably photoswitchable red fluorescent polymer nanoparticles (TPFPNs) through a facile miniemulsion polymerization in this study. TPFPNs contained a high quantum yield of red fluorescence dye, 1,6,7,12-tetra(p-tBu-phenoxy)-3,4,9,10-di(anhydride) perylene (TBPDI) as donor and a thermostably photochromic diarylethene derivative (DTEDA) as acceptor. When DTEDA changed from its opened-ring state (DTEDA-o) to its closed-ring form (DTEDA-c) after UV irradiation, fluorescence resonance energy transfer (FRET) process occurred from TBPDI to DTEDA-c, which induced the transition from red fluorescence to quenching state. In addition, TPFPNs showed adjustable FRET efficiency, outstanding thermal stability, prominent long-term stability, superior photoreversibility, as well as high contrast of on/off fluorescence. Moreover, TPFPNs were successfully used for photo-rewritable patterning and reversible fluorescence bioimaging in Zebrafish.

Interfacial Assembly and Jamming of Soft Nanoparticle Surfactants into Colloidosomes and Structured Liquids.

Nanoparticle surfactant (NPS) offers a powerful strategy to generate all-liquid constructs that integrate the inherent properties of the NPs into 3D architectures. Here, using the co-assembly of fluorescent polymeric nanoparticles and amine-functionalized polyhedral oligomeric silsesquioxane, the assembly and jamming behavior of a new type of NPS at the oil-water interface is uncovered. Unlike "solid" inorganic nanoparticles, "soft" polymeric nanoparticles can reorganize when jammed, leading to a relaxation and deformation of the interfacial assemblies, for example, the 3D printed sugar-coated haw stick-like liquid tubules. With NPS serving as emulsifiers, stable Pickering emulsions are prepared that can be converted into robust colloidosomes with pH responsiveness, showing numerous potential applications for encapsulation and controlled release.

Delicate and Independent Manipulation of Dynamic Fluorescence Behavior of Polymer Nanoparticles Based on a Core-Shell Strategy.

Fluorescent polymer nanomaterials with dynamic fluorescence properties hold great potential in many advanced applications, including but not limited to information encryption, adaptive camouflage, and biosensors. The key to improving the application value of materials is to establish an accurate control strategy for dynamic fluorescence behavior. Herein, we develop a core-shell engineering strategy to precisely and independently manipulate the dynamic fluorescence behavior through the shell polymeric matrix. The core-shell fluorescent polymer nanoparticles (CS-FPNPs) are constructed through a sequential process of miniemulsion polymerization and seeded emulsion polymerization. Taking advantage of the core-shell structure, the rigid core matrix ensures the strong initial emission of AIE units, while the photoisomerization behavior of spiropyrane (SP) units is delicately and independently regulated by the rigidness of the shell matrix. Thereby, CS-FPNPs exhibit bright time-dependent reversible dynamic fluorescence behavior under alternating UV/vis irradiation. Benefited from the excellent processability and film formation ability, we have successfully applied CS-FPNPs to dynamic decorative painting, warning labels, and dynamic QR code security. Impressively, the fluorescence manipulation strategy based on core-shell engineering allows the independent regulation of specific luminescent units in complicated emission systems to accurately embody designed emission behavior.

Inhalable Formulation Based on Lipid-Polymer Hybrid Nanoparticles for the Macrophage Targeted Delivery of Roflumilast.

Here, novel lipid–polymer hybrid nanoparticles (LPHNPs), targeted to lung macrophages, were realized as potential carriers for Roflumilast administration in the management of chronic obstructive pulmonary disease (COPD). To achieve this, Roflumilast-loaded fluorescent polymeric nanoparticles, based on a polyaspartamide-polycaprolactone graft copolymer, and lipid vesicles, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-phosphoethanolamine-N-(polyethylene glycol)-mannose, were properly combined using a two-step method, successfully obtaining Roflumilast-loaded hybrid fluorescent nanoparticles (Man-LPHFNPs@Roflumilast). These exhibit colloidal size and a negative ζ potential, 50 wt % phospholipids, and a core–shell-type morphology; they slowly release the entrapped drug in a simulated physiological fluid. The surface analysis also demonstrated their high surface PEG density, which confers mucus-penetrating properties. Man-LPHFNPs@Roflumilast show high cytocompatibility toward human bronchial epithelium cells and macrophages and are uptaken by the latter through an active mannose-mediated targeting process. To achieve an inhalable formulation, the nano-into-micro strategy was applied, encapsulating Man-LPHFNPs@Roflumilast in poly(vinyl alcohol)/leucine-based microparticles by spray-drying.

Photo-pH dual stimuli-responsive multicolor fluorescent polymeric nanoparticles for multicolor security ink, optical data encryption and zebrafish imaging

Stimuli-responsive fluorescent polymeric nanoparticles are widely used in bioimaging, anti-counterfeiting and data encryption due to their advantages of simple preparation, good water-dispersibility, high brightness and photostability. In this paper, novel photo-pH dual stimuli-responsive multicolor fluorescent polymeric nanoparticles (SMFPNs) were fabricated via combination of one-pot miniemulsion polymerization and surface modification. Based on fluorescence resonance energy transfer (FRET) principle, 4-ethoxy-9-allyl-1,8-naphthalimide (EANI), fluorescein isothiocyanate (FITC) and spiropyran-linked methacrylate (SPMA) can be used to constitute three pairs of FRET systems. In the nanoparticles, the blue fluorescence of EANI (energy donor) decreases and the green fluorescence of FITC (energy receptor) increases via increasing pH. While pH decreases, it can return to blue fluorescence. Meanwhile, after UV light irradiation, SPMA converts from non-fluorescent spiropyrans (SP) state to red fluorescent merocyanine (MC) state, the transformation from blue or green emission to red emission can be realized. When irradiated with visible light, it reverts to its original blue or green fluorescence. Therefore, the system can achieve the multi-color transformation of blue, green and red under changing pH and illumination conditions. In addition, the as-prepared nanoparticles also exhibited high fluorescence contrast, rapid photo-responsiveness and excellent photoreversibility. Therefore, SMFPNs displayed great potential in the fields of multicolor security ink, advanced anti-counterfeiting, multilevel data encryption and in vivo bioimaging.

Nonconjugated fluorescent polymer nanoparticles by self-assembly of PIMA-g-β-CD for live-cell long-term tracking

Fluorescent non-conjugated nanoparticles without any π-aromatic building blocks are of great interest in biological applications due to their low cytotoxicity and biocompatibility. Herein, the non-conjugated AIE-active polymer nanoparticles bearing β-cyclodextrin (β-CD-PNs) were obtained through self-assembly of amphiphilic poly(isobutylene-alt-maleic anhydride)-g-β-CD (PIMA-g-β-CD). Unexpectedly, β-CD-PNs without conventional AIE fluorophores showed strong fluorescence emission in the aggregated state, excellent photostability and water-solubility. More interestingly, β-CD-PNs showed excellent biocompatibility and low biotoxicity after being co-incubated with HeLa cells and passaged several times. As a result, the strong blue fluorescence signals could still be detected in HeLa cells after up to 15 generations of passages and showed complete cell morphology. Furthermore, β-CD-PNs could also be used in zebrafish for bioimaging. The results indicated that β-CD-PNs was a good choice as a tracer for long-term cell tracking and in vivo imaging agent. Our research provided an effective strategy for developing low-toxicity bioprobes based on β-CD.

FRET-mediated quenching of BODIPY fluorescent nanoparticles by methylene blue and its application to bacterial imaging.

High resolution and agood signal to noise ratio are a requirement in cell imaging. However, after labelling with fluorescent entities, and after several washing steps, there is often an unwanted fluorescent background that reduces the images resolution. For this purpose, we developed an approach to remove the signal from extra-cellular fluorescent nanoparticles (FNPs) during bacteria imaging, without the need forany washing steps. Our idea is to use methylene blue to quench > 90% ofthe emission of BODIPY-based fluorescent polymer nanoparticle by a FRET process. This "Hide-and-Seek Game" approach offers a novel strategy to apply fluorescence quenching in bioimaging to improve image accuracy.

Synthesis of Inherently Fluorescent Core–Shell Nanoparticles for Cell Imaging and Targeting Therapy: An In Vitro Evaluation

AbstractFluorescent polymer nanoparticles (NPs) have great potential as bioimaging and therapeutic agents in the biomedical field. Here, a subtle method is developed to synthesize inherently fluorescent core–shell NPs with diameters less than 100 nm. The permanent fluorescence comes from the rigid conjugated structure between benzene and chloromethyl groups in the crosslinked poly(chloromethylstyrene) (PCMSt) core, which is able to be applied for the determination of Fe3+ with a detection limit of 1.39 × 10−6 m. It is further demonstrated that the galactose modification (poly (6‐O‐acryloyl‐d‐galactose), PADGal) shell can efficiently· facilitate the selective internalization of NPs by human hepatocellular carcinoma cells (HepG2), and the cells are more prone to uptake the NPs with medium crosslinking degree. The hydrophobic anticancer drug 10‐hydroxycamptothecin (HCPT) is then loaded onto PADGal@PCMSt NPs. Benefiting from the specific interactions between asialoglycoprotein (ASGP) receptors and the galactose moiety, the PADGal@PCMSt NPs can deliver HCPT with the highest efficiency to HepG2 cells in comparison with the human cervical cancer cells (HeLa), the human alveolar adenocarcinoma basal epithelial cells (A549), the mouse breast cancer cells (4T1), and the mouse fibroblast cells (NIH3T3). The present study provides a new strategy to build small‐size fluorescent polymer NPs with both bioimaging and therapeutic functions.