RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.

Engineered polymer nanoparticles incorporating L-amino acid groups as affinity reagents for fibrinogen

Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid monomers.Five kinds of L-amino acids were acryloylated to obtain functional monomers:L-phenylalanine(Phe)and L-leucine(Leu)with hydrophobic side chains,L-glutamic acid(Glu)with negative charges,and L-lysine(Lys)and L-arginine(Arg)with positive charges.After incubating the NPs with fibrinogen,g-globulin,and human serum albumin(HSA)respectively,the NPs that incorporated Nacryloyl-Arg monomers(AArg@NPs)showed the strongest and most specific binding affinity to fibrinogen,when compared with g-globulin and HSA.Additionally,the fibrinogen-AArg binding model had the best docking scores,and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them.The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay,as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture.AArg@NPs had a strong selectivity for,and specificity to,fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.

Multifunctional conjugated polymer nanoparticles for photoacoustic-based multimodal imaging and cancer photothermal therapy

Photoacoustic imaging(PAI)is a hybrid imaging method based on photoacoustic(PA)effects,which is able to capture the structure,function,and molecular information of biological tissues with high resolution.To date,therapeutic techniques under the guidance of PAI have provided new strategies for accurate diagnosis and precise treatment of tumors.In particular,conjugated polymer nanoparticles have been extensively inspected for PA-based cancer theranostics largely due to their superior optical properties such as tunable spectrum and large absorption coefficient and their good biocompatibility,and abundant functional groups.This mini-review mainly focuses on the recent advances toward the development of novel conjugated polymer nanoparticles for PA-based multimodal imaging and cancer photothermal therapy.

Rational design of biodegradable semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photodynamic therapy

Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.

Gadolinium-containing semiconducting polymer nanoparticles for magnetic resonance/fluorescence dual-modal imaging and photothermal therapy of oral squamous cell carcinoma

Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.

Biocompatible Chemically Fueled Transient Polymer Nanoparticles for Temporally Programmable in Vivo Imaging

Chemically fueled dissipative self-assembly paves the way for innovative materials with lifelike properties and functions.Achievement of nonequilibrium systems with biocompatibility and biofunctions remains an important and challenging task.Here,we present biocompatible chemically fueled transient polymer nanoparticles and their applications in temporally programmable in vivo imaging.The lifetime of the transient polymer nanoparticles can be tuned by varying the concentration of polymer,adenosine triphosphate,and phosphatase.Moreover,the transient assembly of polymer nanoparticles can be paused for storage and then subsequently restored.The transient polymer nanoparticles exhibit good biocompatibility.Notably,we implement in vivo imaging in a temporally programmable fashion by using an autonomous fluorescence modulator of transient nanoparticles assembled from polymers with a fluorescence moiety.The results in this work provide a valuable way to achieve nonequilibrium self-assembly of synthetic systems with good biocompatibility and programmable biofunctions,accelerating innovative developments of nonequilibrium soft biomaterials.

Polymer nanoparticles with dendrimer-Ag shell and its application in catalysis

Polymer nanoparticles with dendrimer-Ag shell were prepared and their application in catalytic reduction of 4-nitrophenol （4-NP） was investigated. Cross-linked polystyrene （PS） microspheres were prepared through dispersion copolymerization of styrene, acrylic acid and crosslinking monomer 1, 2- divinylbenzene. PS microspheres with average size of 450 nm and narrow size distribution were used as support for the immobilization of dendrimer-Ag shell, The polyamidoamine （PAMAM） dendrimer shell was successively grafted onto the surface ofPS microspheres through repetitive Michael addition reaction of methyl acrylate （MA） and amidation of the obtained esters with large excess of ethylenediamine （EDA）. Silver nanoparticles were formed directly inside the PAMAM shell through reduction with NaBH4. The resulting PS@PAMAM-Ag nanopartides were packed in a stainless steel column and used successfully for catalytic reduction of 4-NP. This technique for packing catalytic polymer particles in a column could imnrove the efficiency of using the metal catalyst and the tedious seuaration in catalytic reaction.

Platinum Atoms Dispersed in Single-chain Polymer Nanoparticles

The intramolecular cross-linking of single polymer chains can form single-chain nanoparticles(SCNPs),which have many applications.In this study,styrenic copolymers with pendent triphenylphosphine as the coordination site for platinum ions(Pt(Ⅱ))and benzocyclobutene as the latent reactive groups are synthesized.Triphenylphosphine groups in the chains can coordinate Pt(Ⅱ)and aid slight single-chain folding in dilute solution.The intramolecular cross-linking caused by the ring-open reaction of benzocyclobutene completes the single-chain collapse and forms stable SCNPs in dilute solution.Pt(Ⅱ)embedded in SCNPs can be further reduced to platinum atoms(Pt(0)).Pt(0)steadily and atomically dispersed in SCNPs exhibits better catalytic properties than normal polymer carried platinum particles do for the reduction of p-nitrophenol to p-aminophenol.

On the origin and regulation of ultrasound responsiveness of block copolymer nanoparticles

Noninvasive ultrasound is more convenient and easily accessible for controlled drug delivery of polymeric nanoparticles than many other stimuli.However,controlled ultrasound responsiveness is rather challenging as the mechanism is still unclear.In this article,we disclose the origin and the key regulating factors of ultrasound responsiveness of block copolymer nanoparticles such as simple vesicles,framboidal vesicles,lamellae,beads-like micelles and complex micelles that are self-assembled from a range of poly(ethylene oxide)-b-polymethacrylates based model copolymers.We discover that the intrinsic ultrasound responsiveness of block copolymer nanoparticles thermodynamically originates from their metastable states,and its expression kinetically relates to the mobility of the hydrophobic segments of block copolymers.Specifically,the self-assembly temperature(Ts) that has been usually considered as a less important factor in most of macromolecular self-assembly systems,and the solvents for the selfassembly are two dominant regulating factors of the ultrasound responsiveness because they determine the thermodynamic state(metastable or stable) of nanoparticles.For example,simple vesicles with good or excellent ultrasound responsiveness can be prepared in THF/water when the Tsis around or slightly below the glass transition temperature(Tg) of the hydrophobic segment of the block copolymer because the combination of this solvent with this Tsfacilitates the formation of metastable vesicles.By contrast,thermodynamically stable solid nanoparticles such as spherical micelles and lamellae(mainly formed in DMF/water)are not sensitive to ultrasound at all,neither are the vesicles in THF/water at stable states when the Tsis highly above Tg.In addition,we unravel that the responsive rate is highly dependent on the sonication temperature(Tu),i.e.,the higher the Tu,the faster the rate.Overall,the above important findings provide us with a fresh insight into how to design ultrasound-responsive nanoparticles and may open new avenues for synthesizing translational noninvasively responsive drug carriers.

Glycyrrhizic Acid-Loaded Poly-ɛ-Caprolactone Nanoparticles Decrease PRRSV Infection in MARC-145 Cells

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.

Plugging property and displacement characters of a novel high-temperature resistant polymer nanoparticle

The goal of the research was to investigate the profile control and oil displacement characteristics of the polymer nanoparticles after high temperature swelling.The displacement parameters showed considerable influence on the plugging effect of the high-temperature swelled polymer nanoparticles,such as the core permeability,concentration of nanoparticles in the suspension,swelling time and swelling temperature,which makes it flexible to control the plugging effect by controlling displacement experiments conditions.Experimental results show that polymer nanoparticles dispersion system with a concentration of 500 mg/L is suitable for cores plugging with a permeability of 30×10^(-3)-150×10^(-3)μm^(2),even after aging at 150℃ for three months.The shunt flow experiments show that when the displacement factors are optimal values,the polymer nanoparticles after high temperature swelling to plug the high-permeability layer selectivity and almost do not clog the low-permeability layer.Oil recovery of homogeneous artificial core displacement experiment and a heterogeneous double-tube cores model are increased by 20%and 10.4%on the basis of water flooding.The polymer nanoparticles can be a great help for petroleum engineers to better apply this deep profile control and flooding technology.

A"donor–acceptor"structured semiconductor polymer for near infrared fluorescence imaging guided photodynamic therapy

Near infrared(NIR)fluorescence imaging guided photodynamic therapy(PDT)is a technique which has been developed in many clinical trials due to its advantage of real-time optical monitoring,specific spatiotemporal selectivity,and minimal invasiveness.For this,photosensitizers with NIR fluorescence emission and high^(1)O_(2)generation quantum yield are highly desirable.Herein,we designed and synthesized a"donor-acceptor"(D-A)structured semiconductor polymer(SP),which was then wrapped with an amphiphilic compound(Pluronic■F127)to prepare water-soluble nanoparticles(F-SP NPs).The obtained F-SP NPs exhibit good water solubility,excellent particle size stability,strong absorbance at deep red region,and strong NIR fluorescent emission characteristics.The maximal mass extinction coe±cient and fluorescence quantum yield of these F-SPs were calculated to be 21.7 L/(g·cm)and 6.5%,respectively.Moreover,the^(1)O_(2)quantum yield of 89%for F-SP NPs has been achieved under 635 nm laser irradiation,which is higher than Methylene Blue,Ce6,and PpIX.The outstanding properties of these F-SP NPs originate from their unique D-A molecular characteristic.This work should help guide the design of novel semiconductor polymer for NIR fluorescent imaging guided PDT applications.

Application of a validated HPLC-PDA method for the determination of melatonin content and its release from poly(lactic acid)nanoparticles

Melatonin is a natural hormone and with the advancement of age its production declines and thereby may result in some neurological disorders. Exogenous administration of melatonin has been suggested as a neuroprotective agent. Due to its low oral bioavailability, the loading of melatonin in polymeric nanoparticles could be an important tool to effectively use exogenous melatonin. The quantification of the incorporated drug within polymeric nanoparticles is an important step in nanoparticles characterization. An analytical method using high performance liquid chromatography equipped with photodiode array detector （HPLC-PDA） was developed and validated for melatonin determination in poly （lactic acid） nanoparticles obtained by a single emulsion-solvent evaporation technique. The melatonin in vitro release profile also was determined by the HPLC method. Mobile phase consisted of acetonitrile： water （65：35, v/v） pumped at a flow rate of 0.9 mL/min, in the isocratic mode and PDA detector was set at 220 nm. The method was validated in terms of the selectivity, linearity, precision, accuracy, robustness, limits of detection and quantification. Analytical curve was linear over the concentration range of 10-100 ~tg/mL, and limits of detection and quantification were 25.9 ng/mL and 78.7 ng/mL, respectively. The mean recovery for melatonin was 100.47% （RSD = 1.25%, n = 9）. In the intra- and inter- assay, the coefficient of variation was less than 2%. Robustness was proved performing changes in mobile phase, column temperature and flow rate. The method was suitable for the determination of melatonin encapsulation efficiency in poly（lactic acid） nanopartieles and for the evaluation of melatonin in vitro release profile.

Synthesis and Characterization of Natural Polymer/Inorganic Antibacterial Nanocomposites

In order to increase antibacterial abilities and avoid the aggregation of nanoparticle, Ag- ZnO nanocomposites were studied in the network structure which contains bonds, and these bonds are formed by hydrolysis reaction between Ti（TBOU）4（TBOT） and the water that in Persimmon tannin solution. The size and morphology of Ag-ZnO nanocompos：tes were investigated by scanning electron microscopy （SEM） and field emission scanning electron microscopy（FE-SEM）. The antibacterial properties of nanocomposites were examined by minimal bactericidal concentration（MBC）. Results showed that this kind of antibacterial nanocomposites composites（ANPs） have excellent antibacterial abilities and without aggregation.

<i>In-Silico</i>Validation and Development of Chlorogenic Acid (CGA) Loaded Polymeric Nanoparticle for Targeting Neurodegenerative Disorders

Background: Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also been widely investigated in Neurodegenerative disorders (NDDs) and Chlorogenic acid (CGA), a polyphenolic compound having potential anti-inflammatory and anti-oxidative properties, emerged as a promising compound in ameliorating NDDs. Owing to its poor stability, bioavailability and release kinetics, CGA needed a suitable nanocarrier based pharmaceutical design for targeting NDDs. Objective: The current study is aimed at the in-silico validation of CGA as an effective therapeutic agent targeting various NDDs followed by the fabrication of polymeric nanoparticles-based carrier system to overcome its pharmacological limitations and improve its stability. Methods: A successful in-silico validation using molecular docking techniques along with synthesis of CGA loaded polymeric nanoparticles (CGA-NPs) by ionic gelation method was performed. The statistical optimisation of the developed CGA-NPs was done by Box Behnken method and then the optimized formulation of CGA-NPs was characterised using particle size analysis (PSA), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (FTIR) along with in-vitro release kinetics analysis. Results & Conclusion: The results attained exhibited average particle size of 101.9 ± 1.5 nm, Polydispersibility (PDI) score of 0.065 and a ZP of −17.4 mV. On a similar note, TEM results showed a size range of CGA-NPs between 90 - 110 nm with a spherical shape of NPs. Also, the data from in-vitro release kinetics showed a sustained release of CGA from the NPs following the first-order kinetics suggesting the appropriate designing of nanoformulation.

Preparing cyclic polymers at high concentrations via self-folding cyclization technique by adjusting the contents of hydrophilic units in linear precursors

Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-folding cyclization technique at high concentrations.Linear poly((oligo(ethylene glycol)acrylate)-co-(dodecyl acrylate))(P(OEGA-co-DDA))precursors with different ratios of hydrophilic and hydrophobic moieties were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization using a bifunctional chain transfer agent with two anthryl end groups.The amphiphilic linear precursors underwent the self-folding process to generate polymeric nanoparticles in water.By irradiating the aqueous solution of the nanoparticles with 365 nm UV light,cyclic polymers were synthesized successfully via coupling of anthryl groups.The effects of the ratios of hydrophilic and hydrophobic moieties in linear P(OEGA-co-DDA)copolymers and polymer concentration on the purity of the obtained cyclic polymers were explored in detail via ^(1)H nuclear magnetic resonance(^(1)H NMR),dynamic light scattering(DLS),UV‒visible(vis)analysis,three-detection size exclusion chromatography(TD-SEC)and transmission electron microscopy(TEM).It was found that by adjusting the content of the hydrophilic segments in linear precursors,single chain polymeric nanoparticles(SCPNs)can be generated at high polymer concentrations.Therefore,cyclic polymers with high purity can be constructed efficiently.This method overcomes the limitation of traditional ring-closure method,which is typically conducted in highly dilute conditions,providing an efficient method for the scalable preparation of cyclic polymers.

PHOTOSWITCHABLE NANOFLUOROPHORES FOR INNOVATIVE BIOIMAGING

Photosensitive fluorescent probes have become powerful tools in chemical biology and molecular biophysics,which are used to investigate cellular processes with high temporal and spatial resolution.Accordingly,photosensitive fluorescent probes,including photoactivatable,photoconvertible,and photoswitchable fluorophores,have been extensively developed during the past decade.The photoswitchable fluorophores have received much attention because they highlight cellular events clearly.This minireview summarizes recent advances of using reversibly photoswitchable fluorophores and their applications in innovative bioimaging.Photoswitchable fluorophores include photoswitchable fluorescent proteins,photoswitchable fluorescent organic molecules(dyes),and photoswitchable fluorescent nanoparticles.Several strategies have been developed to synthesize photoswitchable fluorophores,including engineering combination proteins,chemical synthesis,polymerization,and self-assembly.Here we concentrate on polymer nanoparticles with optically switchable emission properties:either fluorescence on/offor dualalternating-color fluorescence photoswitching.The essential mechanisms of fluorescence photoswitching enable different types of photoswitchable fluorophores to change emission intensity or wavelength(color)and thus validating the basis of the fluorescence on/offor dual-color photoswitching design.Generally the possible applications of any fluorophores are to label biological targets,followed by specific imaging.The newly developed photoswitchable fluorophores enable super-resolution fluorescence imaging because of their photosensitive emission.Finally,we summarize the important area regarding future research and development on photoswitchable fluorescent nanoparticles.

Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)core and a surface coating of lipid monolayer.Membrane emulsification technique was used to obtain uniform-sized Lipid NPs.Ovalbumin(OVA)was used as a model vaccine.Compared with the pure PLGA NPs,the Lipid NPs achieved higher loading capacity(LC)and entrapment efficiency(EE)for the encapsulated OVA.An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal(GI)environment for a long time.In addition,a human microfold cell(M-cell)transcytotic assay demonstrated that due to a lipid layer structure on the particle surface,the Lipid NPs showed higher affinity to the M-cells.Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells,the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.

On-demand assembly of polymeric nanoparticles for longer-blood-circulation and disassembly in tumor for boosting sonodynamic therapy

Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ~80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (~0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H_(2)O_(2) into O_(2) to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.

Responsive Polymeric Nanoparticles for Biofilm-infection Control

With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens.To address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared recently.The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms.The advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.