Fluorescent Polymer Nanoparticles Research Articles

From a Molecular Toolbox to a Toolbox for Photoswitchable Fluorescent Polymeric Nanoparticles

AbstractSwitchable organic fluorescent materials are attracting much interest in many fields including flexible display, information storage, anti‐counterfeit, and bioimaging, due to their prominent properties and relatively low cost. Herein, a class of novel photoswitchable fluorescent polymeric nanoparticles (PFPNs) toolbox that shows switchable full‐colored emission including white light is described. This nanoparticles toolbox consists of a series of reversibly photoswitchable and non‐PFPNs with red, green, and blue fluorescence, and is built up from three primary fluorescent dyes and a photochromic diarylethene molecule, through a facile one‐pot miniemulsion method. The as‐prepared PFPNs display the merits of high fluorescence resonance energy transfer efficiency and fluorescence quantum yield, rapid responsiveness, prominent photoreversibility, and brilliant long‐term fluorescence stability (≈6 weeks). They enable switchable emission between white light and any visible color on‐demand in both solution and film states. Their potential in complex fluorescent encryption and photoswitchable white light‐emitting diode is described and its great potential in anti‐counterfeiting technology, data encryption, and the next generation of optoelectronic materials is foreseen.

Fabrication and biological imaging of hydrazine hydrate cross-linked AIE-active fluorescent polymeric nanoparticles

Amphiphilic copolymers play a paramount role in the fabrication of fluorescent polymeric nanoparticles (FPNs) through the self-assembly procedure. In this work, novel hydrazine hydrate cross-linked amphiphilic poly(PEG‑co‑FHMA) copolymers were constructed via reversible addition-fragmentation chain transfer (RAFT) polymerization, containing an aggregation-induced emission (AIE) active hydrophobic moiety and a hydrophilic poly(ethylene glycol) (PEG) group. Different characterization techniques have been employed to confirm their successful synthesis. Due to their amphiphilic property, the resulting poly(PEG‑co‑FHMA) copolymers can self-assemble into FPNs in aqueous solution and form poly(PEG‑co‑FHMA) FPNs with size ranging from 100 to 200 nm. The investigation of photophysical properties demonstrated poly(PEG‑co‑FHMA) FPNs possess strong fluorescence, large Stokes shift, excellent AIE characteristic, low critical micelle concentration and remarkable photostability. Biological assay results suggested that these cross-linked AIE-active FPNs are of low toxicity and excellent cell dyeing performances. All of these features make them promising candidates for biomedical applications. As compared with typical AIE-active FPNs based on the synthetic AIE-active compounds, the novel cross-linked AIE-active FPNs based on the Schiff base is rather simple, good designable and universal. More importantly, this strategy could also be adopted for preparation of a large number of AIE-active FPNs because of the well designability of copolymers and salicylaldehyde derivatives. Thus this work will provide a novel route for preparation of multifunctional AIE-active FPNs in a rather facile manner.

Highly Efficient Energy Transfer Cassettes by Assembly of Boronic Acid Derived Salicylidenehydrazone Complexes

AbstractEnergy transfer cassettes that build on the platform of boronic acid derived salicylidenehydrazone (BASHY) complexes were prepared. The functional flexibility of the BASHY chromophore was underpinned by its tunable role as energy donor or acceptor, integrated in compact and non‐conjugated bichromophoric dyads. The energy transfer is highly efficient (ΦET>0.95) and is assumed to proceed mainly via a through‐bond mechanism. Both constituent chromophores benefit mutually from their integration in the cassettes: a) The pseudo Stokes shift is increased to 110–200 nm; b) the antenna (donor) chromophore improves the light absorption of the acceptor chromophore; and c) the emission window of the BASHY chromophore is expanded in the BASHY‐Bodipy dye without using strategies that compromise the observation of high quantum yields. The application of the cassettes for the formulation of fluorescent polymeric nanoparticles, that can be internalized in cells and observed by fluorescence imaging, was demonstrated using the BASHY‐Bodipy dye as an example.

Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced Cell Death in MCF-7 Cells.

Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 μg/mL, 12.5 μg/mL, 50 μg/mL, 75 μg/mL, and 100 μg/mL) of FMSP-nanoparticles alone and in combination with 50 μg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4′,6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer cell viability was decreased to 55.40% when treated with FMSP-nanoparticles alone, whereas when cancer cells were treated with FMSP-nanoparticles along with crude clove extracts, the cell viability was drastically decreased to 8.50%. Both morphological and quantitative data suggest that the combination of FMSP-nanoparticles plus crude clove extracts are more effective in treating cancer cells and we suggest that the combination treatment of nanoparticles along with clove extracts hold a great promise for the cancer treatments.

Fluorescent magnetic submicronic polymer (FMSP) nanoparticles induce cell death in human colorectal carcinoma cells

Nanoparticles have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. The aim of the present study is to examine whether fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) have any impact on human colorectal cancer cells. In the present study, we have tested FMSP-nanoparticles with an average size of 100–200 nm on human colorectal carcinoma cells (HCT-116) to check their cytotoxic and anti-cancer capabilities. The effects of FMSP-nanoparticles on cancer cells were observed after 6 h, 24 h and 48 h intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4lue-diamidino-2-phenylindole (DAPI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Our MTT analysis results revealed that FMSP-nanoparticles produced dose-dependent effects on cancer cells, FMSP-nanoparticles with dose of 1.25 µg/mL did not decrease cell survivability, whereas dosages of 12.5 µg/mL and 50 µg/mL respectively showed 23.59% and 59.47% decrease in the cancer cell survivability. In conclusion, our results demonstrate FMSP-nanoparticles have a potential anti-cancer capability and hold a great promise for colon cancer treatments.

Intrinsically fluorescent and highly functionalized polymer nanoparticles as probes for the detection of zinc and pyrophosphate ions in rabbit serum samples

Intrinsically fluorescent polymer nanoparticles (F-PNPs) were synthetized from 2-hydroxy-5-methylisophthalaldehyde and melamine by solvothermal method. F-PNPs can emit strong yellow green fluorescence at 542 nm without the conjugation to any external fluorescent agent and surface modification. Owing to the abundant amino and hydroxyl groups on their surface, the F-PNPs possess multiple binding sites, good biocompatibility and excellent water-solubility. Addition of Zn2+ to the F-PNPs solution resulted in a blue shift (Δλ=40 nm) with obvious enhancement in the fluorescence intensity at 502 nm; while there was negligible change in the presence of other metal ions. The subsequent treatment with pyrophosphate (PPi) can cause fluorescence recovery of F-PNPs by pulling the Zn2+ out of the coordination cavity of F-PNPs-Zn2+ nanocomposites. No interference was observed from other anions and nucleotides, making the F-PNPs-Zn2+ ensembles highly sensitive and selective nanoprobes for PPi. The detection limit is 2.75 × 10−8 M/L and 7.63 × 10−8 M/L for Zn2+ and PPi, respectively. The proposed nanoprobes were then used for detecting the recovery of Zn2+ and PPi in rabbit serum samples, which were found to be 99.4–104.2% and 98.6–104.7%, respectively. The present strategy for the fabrication of nanoparticles may offer a new sight for the preparation of polymer nanostructures. The F-FNPs based probes can provide an accurate method for the detection of Zn2+ and PPi in serum samples.

FMSP-Nanoparticles Induced Cell Death on Human Breast Adenocarcinoma Cell Line (MCF-7 Cells): Morphometric Analysis.

Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7). We tested different concentrations (1.25, 12.5 and 50 µg/mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.

Synthesis and biological imaging of cross-linked fluorescent polymeric nanoparticles with aggregation-induced emission characteristics based on the combination of RAFT polymerization and the Biginelli reaction

Fluorescent probes have long been regarded as tools for imaging living organisms with advantages such as high sensitivity, good designability and multifunctional potential. Many fluorescent probes, especially the probes based on aggregation-induced emission (AIE) dyes, have received increasing attention since the AIE phenomenon was discovered. These AIE dye-based fluorescent probes could elegantly overcome the notorious quenching effect caused by aggregation of conventional organic dyes. However, it is still difficult to directly apply these AIE-active dyes for biomedical applications owing to their hydrophobic nature. Therefore, the development of novel and facile strategies to endow them with water dispersibility is of critical importance. In this work, we exploit an efficient and simple strategy to fabricate an AIE dye-based fluorescent copolymer through the combination of reversible addition-fragmentation chain transfer and the Biginelli reaction. Moreover, the copolymer can self-assemble to fluorescent polymeric nanoparticles (FPNs) in water solution. Hydrophilic poly(PEGMA-co-AEMA) was reacted with the AIE-active dye 4′,4‴-(1,2-diphenylethene-1,2-diyl)bis([1,1′-biphenyl]-4-carbaldehyde (CHO-TPE-CHO) to form amphiphilic luminescent polymers using urea as the connection bridge. The successful synthesis of the final products (poly(PEGMA-co-AEMA-TPE) FPNs) was confirmed by various instruments. Furthermore, Transmission electron microscopy (TEM) images manifest that poly(PEGMA-co-AEMA-TPE) copolymers will self-assemble into spherical nanoparticles in aqueous environments with sizes between 100 nm and 200 nm. The cell uptake and bioimaging experiment confirm that poly(PEGMA-co-AEMA-TPE) FPNs have excellent biocompatibility and emit strong green fluorescence in a cellular environment. Thus, poly(PEGMA-co-AEMA-TPE) FPNs are excellent candidates for biomedical applications.

Synthesis and biological imaging of fluorescent polymeric nanoparticles with AIE feature via the combination of RAFT polymerization and post-polymerization modification

In recent years, florescent polymeric nanoparticles (FPNs) containing aggregation-induced emission (AIE) fluorogens have received great intention for their potential applications in biological imaging and theranostic nanomedicine. Herein, we have developed AIE-active FPNs through a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and post-polymerization modification strategies. The salicylaldehyde (SA) containing zwitterionic copolymers are fabricated via RAFT polymerization and further modified by benzophenone hydrazone (BPH) via Schiff base reaction. The obtained AIE-active amphiphilic copolymers BPH-poly(FHMA-co-MPC) can self-assemble in aqueous solution with the hydrophobic fluorogens aggregating together to form the core and the hydrophilic chains to form the protective shell. BPH-poly(FHMA-co-MPC) and the resulting FPNs are characterized by 1H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy. Results demonstrate that BPH-poly(FHMA-co-MPC) are successfully synthesized and as-prepared BPH-poly(FHMA-co-MPC) FPNs exhibit desirable morphology and size, good dispersibility, high brightness, remarkable photostability and large Stokes shifts. More importantly, through cytotoxicity test and cell uptake behavior, these BPH-poly(FHMA-co-MPC) FPNs show low toxicity and excellent cell dyeing behavior. Taken together, we have developed a facile and effective method for the fabrication of AIE-active FPNs, which display great potential for biomedical applications.

Entrapment and Rigidification of Adenine by a Photo-Cross-Linked Thymine Network Leads to Fluorescent Polymer Nanoparticles

Photo-cross-linking of nucleobase-containing polymer micelles was observed to result in fluorescent polymer nanoparticles. By varying the micelle assembly conditions, it was possible to probe the origins of this behavior. A number of factors were investigated, including the effect of omitting one of the nucleobases, blocking hydrogen-bonding interactions, detaching the nucleobase from the polymer backbone, and changing the degree of core cross-linking. Spectroscopic investigations were also carried out to further characterize the fluorescent nanoparticles. These data revealed that no new small molecule fluorophores were created during cross-linking and that a dense, hydrogen-bonded network of photodimerized thymine with entrapped adenine was required for fluorescence to arise. We conclude that rigidification and immobilization of adenine in this way leads to the enhancement of an already extant fluorescence pathway and suggests that synergistic covalent and supramolecular entrapment of profluorophores may...

Ultrafast construction and biological imaging applications of AIE-active sodium alginate-based fluorescent polymeric nanoparticles through a one-pot microwave-assisted Döbner reaction

Aggregation-induced emission (AIE) is a unique fluorescence phenomenon that has attracted great interest for various applications especially for the fabrication of AIE-active polymeric nanoparticles. The AIE-active fluorescent polymeric nanoparticles (FPNs) showed attractive optical properties, which could elegantly overcome the lousy aggregation-caused quenching (ACQ) effect of FPNs based on conventional organic fluorogens. Although great advances and progress have been achieved for the fabrication of AIE-active FPNs, the preparation of AIE-active carbohydrate polymers is still challengeable for the poor solubility of carbohydrate polymers in organic solvents. In this work, we reported the sodium alginate-based fluorescent biopolymers (OSA-PA-PhE) with AIE characteristic could be facilely fabricated via an ultrafast one-pot multicomponent reaction (named as Döbner reaction) with the assistance of microwave irradiation. Among the Döbner reaction system, the oxidized sodium alginate (OSA) and AIE-active dye (named as PhE-NH2) were conjugated using pyruvic acid (PA) as the molecular “bridge”. A number of characterization techniques, such as proton nuclear magnetic resonance (1H NMR), fourier transform infrared (FT-IR) spectroscopy, UV–Vis absorption spectroscopy, fluorescent spectroscopy and transmission electron microscopy (TEM), have been utilized to confirm the successful preparation of OSA-PA-PhE biopolymers. The biological evaluation results confirmed that the OSA-PA-PhE FPNs possessed ultrahigh biocompatibility and desirable imaging properties. Moreover, compared with the previous work about FPNs, this work had at least two obvious advantages, one was the original materials of sodium alginate are resourceful, cheaper, and compatible for human tissue and cells, and another was the novel Döbner reaction is a facile conjugation reaction under mild experimental conditions (e.g. catalyst-free, air atmosphere and in the presence of water). Considered the features of microwave-assisted Döbner reaction and OSA, the OSA-PA-PhE FPNs should be of great potential for different biomedical applications.

Facile Synthesis of Gadolinium Chelate-Conjugated Polymer Nanoparticles for Fluorescence/Magnetic Resonance Dual-Modal Imaging.

Fluorescence (FL)/magnetic resonance (MR) dual-modal imaging nanoprobes are significant not only for cutting edge research in molecular imaging, but also for clinical diagnosis with high precision and accuracy. However, synthesis of FL/MR dual-modal imaging nanoprobes that simultaneously exhibit strong fluorescent brightness and high MR response, long-term colloidal stability with uniform sizes, good biocompatibility and a versatile surface functionality has proven challenging. In this study, the well-defined core-shell structured Gd3+ chelate-conjugated fluorescent polymer nanoparticles (Gd-FPNPs) that consist of rhodamine B (RB)-encapsulated poly(methyl methacrylate) (PMMA) cores and Gd3+ chelate-conjugated branched polyethylenimine (PEI) shells, are facilely synthesized via a one-step graft copolymerization of RB-encapsulated MMA from PEI-DTPA-Gd induced by tert-butyl hydroperoxide (TBHP) at 80 °C for 2 h. The mild synthesis route not only preserves the chemical environment for Gd3+ coordination, but also improves optical properties and chemo-/photostability of RB. A high local concentration of outer surface-chelated Gd3+ and their direct interactions with hydrogen protons endow Gd-FPNPs high longitudinal relaxivity (26.86 mM-1 s-1). The uniform spherical structure of Gd-FPNPs facilitates their biotransfer, and their surface carboxyl and amine groups afford them both long-term colloidal stability and cell-membrane permeability. The excellent biocompatibility and FL/MR dual-modal imaging capability of Gd-FPNPs are demonstrated using HeLa cells and mice as models. All the results confirm that Gd-FPNPs fulfill the design criteria for a high-performance imaging nanoprobe. In addition, this study enables such probes to be prepared also by those not skilled in nanomaterial synthesis, and thus promoting the development of novel functional imaging nanoprobes.

Fabrication of Positively Charged Fluorescent Polymer Nanoparticles for Cell Imaging and Gene Delivery.

Development of efficient non-viral gene delivery vector has aroused great attention in the past few decades. In this study, we reported a new gene delivery vector, positively charged fluorescent conjugated polymer nanoparticles (CPNPs), for efficient gene transfection and in-situ intracellular fluorescence imaging. The microscopic and spectroscopic characterizations demonstrated that these CPNPs possess decent fluorescence performance (e.g. with fluorescence quantum yield of 70.7±0.3%) and small size dimension of ~3.6±0.3 nm (DLS result). Fast and efficient cellular translocation capability was observed according to the time-dependent living cell imaging experiments. Nearly all of the cells were loaded with CPNPs after co-incubation for 2 h regardless of the cell type. In comparison with the commonly used gene delivery vector, lipofectamine 2000 (with gene transfection efficiency of 55±5% for pEGFP), the gene expression efficiency with the positively charged CPNPs (70±3% for pEGFP) was improved significantly. Intracellular fluorescence imaging results demonstrated that the CPNPs could actively assemble close to the periphery of nuclei. Disassembly was not observed even 36 h later, which greatly facilitates releasing of pDNA close to the periphery of nuclei and thus promotes the gene transfection efficiency.

Switchable single fluorescent polymeric nanoparticles for stable white-light generation

We describe SFPNs that can alternate luminescence between stable white-light and cyan- or pink-light emission upon photoirradiation or solvent-induced swelling.

Facile fabrication of biodegradable lanthanide ions containing fluorescent polymeric nanoparticles: Characterization, optical properties and biological imaging

The fluorescent polymeric nanoparticles (FPNs) with encapsulated europium complexes have recently emerged as one of the most promising luminescent probes for biomedical applications owing to their unique optical properties, biocompatibility and structure designability. Significant progresses have been made for the preparation of biocompatible trivalent lanthanide ions (Ln3+) fluorescent nanoparticles, whereas, only limited attention was focused on the fabrication of europium ion containing FPNs with biodegradability, high sensitivity and deep penetration. In this work, a facile and simple method was developed to construct biodegradable and biocompatible luminescent polyurethanes (PUs) through a two-step polymerization. In this construction system, diisocyanate-terminating polyethylene glycol (NCO-PEG-NCO) was first synthesized and subsequently conjugated with dihydroxyl modified europium (III) chelates (Eu(TTA)3Phen-OH) to obtain these luminescent PUs. These PUs show amphipathic property and can assemble into core-shell FPNs in aqueous solution and exhibit high water dispersibility. Biological evaluation results suggest that Eu(TTA)3Phen-PEG2000 FPNs possess desirable biocompatibility and great potential for biological imaging applications. Therefore, we expect that the fabrication approach will inspire much research enthusiasm and effort for the preparation of biodegradable luminescent probes.

Fabrication of AIE-active fluorescent polymeric nanoparticles with red emission through a facile catalyst-free amino-yne click polymerization

Fluorescent polymeric nanoparticles (FPNs) as novel probes have attracted more and more attention for biomedical applications owing to their optical properties and multifunctional potential. However, most of FPNs based on conventional organic fluorogens encounter serious aggregation-caused quenching (ACQ) effect. In this work, to overcome these problems, amphiphilic fluorescent copolymers [Poly(PEGY-PhE)] containing aggregation-induced emission (AIE) fluorogens (AIEgens) have been prepared via a facile amino-yne click polymerization under rather mild experimental conditions (catalyst-free and room temperature). The Poly(PEGY-PhE) copolymers can self-assemble into FPNs and be well dispersed in aqueous solution. Fluorescence spectra demonstrate that Poly(PEGY-PhE) FPNs possess strong red fluorescence, excellent photostability and low critical micelle concentration. The biological assays confirm that these AIE-active Poly(PEGY-PhE) FPNs possess low cytotoxicity towards L929 cells and cell dyeing performance. More importantly, this amino-yne click polymerization provides a simple strategy to prepare robust biocompatible fluorescent nanoparticles for biological imaging because of their high efficiency, mild reaction conditions and simple experimental operation procedure.

Self-catalyzed photo-initiated RAFT polymerization for fabrication of fluorescent polymeric nanoparticles with aggregation-induced emission feature

In recent years, the fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) feature have been extensively exploited in various biomedical fields owing to their advantages, such as low toxicity, biodegradation, excellent biocompatibility, good designability and optical properties. Therefore, development of a facile, efficient and well designable strategy should be of great importance for the biomedical applications of these AIE-active FPNs. In this work, a novel method for the fabrication of AIE-active FPNs has been developed through the self-catalyzed photo-initiated reversible addition fragmentation chain transfer (RAFT) polymerization using an AIE dye containing chain transfer agent (CTA), which could initiate the RAFT polymerization under light irradiation. The results suggested that the final AIE-active FPNs (named as TPE-poly(St-PEGMA)) showed great potential for biomedical applications owing to their optical and biological properties. More importantly, the method described in the work is rather simple and effective and can be further extended to prepare many other different AIE-active FPNs owing to the good monomer adoptability of RAFT polymerization.

Ultrafast microwave-assisted multicomponent tandem polymerization for rapid fabrication of AIE-active fluorescent polymeric nanoparticles and their potential utilization for biological imaging

The fabrication and biomedical applications of fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) feature has attracted the most intensive research interest since the first discovery of AIE phenomenon by Tang' group. Although great attention has been devoted to preparation of AIE-active FPNs, an efficient, facile and versatile strategy is still highly desirable to advance their biomedical applications. In this work, a one-pot microwave-assisted multicomponent tandem polymerization was proposed to fabricate AIE-active FPNs based on a microwave-assisted Kabachnik–Fields (KF) reaction, which involves the conjugation of aldehyde group containing polyethylene glycol (CHO-PEG-CHO) and amino-group terminating AIE dye (H2N-PhE-NH2) using diethyl phosphate as the lock. The KF reaction can occur under rather facile and mild experimental conditions (e.g. absent of catalyst and solvents, air atmosphere) with the assistance of microwave irradiation in 5min. The resultant (PEG-DP-PhE) copolymers would self-assemble into FPNs that showed high water dispersibility and enhanced fluorescence intensity. The desirable cytocompatibility and cell uptake efficiency of PEG-DP-PhE FPNs endow their great potential for biomedical applications. Considering the convenience and effectiveness, the method should be promising for fabrication of many AIE-active functional materials with great application potential.

A novel self-catalyzed photoATRP strategy for preparation of fluorescent hydroxyapatite nanoparticles and their biological imaging

Hydroxyapatite (HAp), as an important biomaterial for the regeneration and reconstruction of bone tissue, has attracted more and more attention of researchers and scientists due to its unique structure and compositions. However, the preparation of fluorescent HAp with controllable morphology has achieved only limited success. In this work, we reported a novel strategy to construct the water dispersible fluorescent HAp nanorods via the combination of ligand exchange and metal-free atom transfer radical polymerization (ATRP). The Br-containing fluorescent HAp nanorods with controllable size and morphology were first prepared through hydrothermal treatment. A multifunctional organic molecule (named as PTH-Br) with aggregation-induced emission feature was immobilized on the surface of hydrophobic HAp nanorods through ligand exchange reaction. The PTH-Br could be used as the initiator and catalyst for surface-initiated metal-free ATRP using poly(ethylene glycol) methacrylate as monomer to obtain hydrophilic fluorescent HAp polymer nanoparticles. This strategy successfully endowed HAp nanorods excellent fluorescence properties and favorable water dispersibility but well preserved their regular morphology. Biological assays demonstrated that the HAp-PTH-poly(PEGMA) nanoparticles exhibited good biocompatibility and efficient cell uptake performance. Taken together, we have developed a rather facile strategy based on the surface ligand exchange reaction and metal-free photoATRP to fabricate fluorescent HAp with controllable size and morphology, high water dispersibility and biological properties. These HAp-PTH-poly(PEGMA) nanoparticles should be novel and promising candidates for biomedical applications.

Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier–wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid–polyaspartamide copolymer. The latter was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC–drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers.