A Smart "Sense-and-Treat" Nanoplatform Based on Semiconducting Polymer Nanoparticles for Precise Photothermal-Photodynamic Combined Therapy.

Integrated theranostic nanoplatforms with biomarker recognition and photothermal- and photodynamic (PTT/PDT) therapy is in high demand but remains challenging. Herein, a "sense-and-treat" nanoplatform based on semiconducting polymer nanoparticles (SPNs) for ratiometric bioimaging of phospholipase D (PLD) activity and PTT/PDT combined therapy was proposed. Semiconducting polymer nanoparticles (PSBTBT NPs) serve not only as photothermal agents but also as fluorescent quenchers of Rhodamine B (Rhod B) through a PLD-cleavable linker. Chlorin e6 (Ce6) was used as a photodynamic agent and fluorescence reference. The obtained nanoplatform (PSBTBT-Ce6@Rhod NPs) showed high PDT efficiency and photothermal performance upon single laser irradiation. The PTT/PDT combined therapy achieved more efficient tumor inhibition results as compared with single treatments. In addition, the overexpressed biomarker PLD in tumor tissue will cleave Rhod, leading to the fluorescence recovery of Rhod B and thus allowing the activatable fluorescence imaging of tumor and targeted phototherapy.

Highly sensitive detection of nucleic acids using a cascade amplification strategy based on exonuclease III-assisted target recycling and conjugated polyelectrolytes.

In this paper, a novel ratiometric and cascade amplification strategy was developed by combining the unique signal amplification and effective fluorescence resonance energy transfer (FRET) property of conjugated polymers with the Exo III-assisted target recycling method. The target DNA (ssDNAc) could be hybridized with the duplex-stranded probe to trigger the cyclic digestion of the probe strands and lead to the continuous release of fluorescein from the probe. The proposed strategy thus shows enhanced sensitivity toward target DNA with a detection limit of 0.38 nM, which is more sensitive than the previously reported comparable biosensors based on conjugated polyelectrolytes. Furthermore, this method exhibited an improved performance to discriminate single mismatched targets through an efficient FRET-based ratiometric detection method using a conjugated polymer as a donor and an optical transducer. More importantly, this cascade amplification approach offers the advantages of simplicity, which avoids multiple utilization of probes and complex assay steps required in traditional amplification methods.

Ag+-Adsorbing Semiconducting Polymer Nanosponge for Smart Local Treatment of Wound Infection.

Nanoplatform combined with photothermal therapy (PTT) and silver nanoparticles have been widely used to combat bacterial infections. However, the development of environmentally benign antibacterial nanoplatforms with controllable and long-term antibacterial activity is still challenging. Herein, we synthesized an Ag+-adsorbing organic semiconducting polymeric nanosponge (PDPP3T NPe@Ag+) to realize Ag+ enhanced photothermal anti-infective therapy. Furthermore, the PDPP3T NPe@Ag+ sponge can also spatiotemporally release silver ions in a pH/NIR light-responsive manner for controllable and long-term antimicrobial therapy. Owing to good biocompatibility and controlled release of silver ions, PDPP3T NPe@Ag+ can effectively kill bacteria in vitro and promote wound healing in vivo. We expect that this antimicrobial platform could be utilized as a robust antibacterial agent for infective therapy.

One-pot encapsulation of luminescent quantum dots synthesized in aqueous solution by amphiphilic polymers.

A simple one-pot polymer encapsulation method is developed for group II-VI semiconductor quantum dots (QDs) synthesized in aqueous solution. The micelles of amphiphilic polymers, such as octadecylamine-modified poly(acrylic acid), capture and encapsulate the QDs when the original hydrophilic ligands, namely 3-mercaptopropionic acid (MPA), capped on the CdTe/CdS core/shell QDs are partially or fully exchanged by the hydrophobic ligands, 1-dodecanethiol. The molar ratio of the amphiphilic polymer to QDs plays a crucial role in determining the final morphology of the encapsulated structures, including the number of QDs encapsulated in one polymeric micelle. Importantly, the polymer coating significantly improves the optical properties of the QDs, which enhances the photoluminescence quantum yield by about 50%. Furthermore, the photostability of the amphiphilic polymer-coated QDs is much better than that of the synthesized QDs capped with MPA.

The self-assembly of a hybrid photosensitizer for the synergistically enhanced photodynamic/photothermal therapy.

The simultaneous near-infrared (NIR)-absorbed photodynamic therapy (PDT)/photothermal therapy (PTT) has proved to be a promising approach to increase the antitumor efficiency due to their synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based photosensitizer was designed and synthesized for the enhanced synergistic NIR-absorbed PDT/PTT therapy upon NIR light irradiation. In this strategy, a three-dimensional rigid polyhedral oligomeric silsesquioxane (POSS) block was introduced into the Br-BODIPY molecule to alleviate the aggregation of the photosensitizer. The POSS hybrid BODIPY (Br-BODIPY-POSS) was further functionalized with a biocompatible amphiphilic PEG via a facile thiol-ene "click" reaction, affording Br-BODIPY-POSS-PEG2000 (BBPP). BBPP can self-assemble into nanoparticles, which maintain a competitive photothermal conversion efficiency (ηBBPP = 30.2%) with its counterpart Br-BODIPY-PEG (BBP, ηBBP = 34.5%). Significantly, BBPP exhibited a relatively higher oxygen quantum yield (ΦBBPP = 0.405) than BBP (ΦBBP = 0.175). The in vitro and in vivo experiments showed that BBPP possessed negligible dark cytotoxicity and a better phototherapeutic outcome than BBP. The proof-of-concept of the POSS hybrid photosensitizer offers guidance for the construction of single-component and PDT/PTT-balanced NIR nanoagents to promote the cancer therapeutic efficacy in the future.

Highly stable semiconducting polymer nanoparticles for multi-responsive chemo/photothermal combined cancer therapy.

Rationale: Structural stability and size controllability are critical issues to semiconducting polymer nanoparticles (SPNs), which currently show great potential for theranostic applications. Methods: Herein, multi-responsive semiconducting polymer semi-interpenetrating nanoparticles (PDPP3T@PNIPAMAA IPNs) with highly stable structure and uniform size have been successfully designed by semi-interpenetrating technique. Results: It is proposed for the first time that PDPP3T@PNIPAMAA IPNs were prepared with "reinforced concrete" particle structure, which is even resistant to organic solvent such as ethanol and THF. By adjusting the polymerization time, the obtained PDPP3T@PNIPAMAA IPNs exhibit uniform and controllable particle size with extremely low polydispersity index (~0.037) at 1 h of reaction time. The presence of pH/light/GSH multi-responsive semi-interpenetrating network in PDPP3T@PNIPAMAA IPNs dramatically increase their drug loading efficiency (92.64%), which is significantly higher than previously reported comparable SPNs-based drug delivery systems. Additionally, PDPP3T@PNIPAMAA-DOX IPNs further provide improved therapeutic efficacy by the combination of chemotherapy and photothermal therapy with controllably regulated release of doxorubicin (DOX). In vitro and in vivo results indicate that PDPP3T@PNIPAMAA-DOX IPNs are able to release drugs at controlled rate by pH/light/GSH regulation and offer PAI-guided chemo/photothermal combined therapy with excellent therapeutic efficacy. Conclusions: The semi-interpenetrating network method may be generally extended for the preparation of a wide range of organic polymer nanoparticles to achieve ultrahigh structural stability, precise particle size controllability and excellent drug loading capacity.

pH/NIR-responsive semiconducting polymer nanoparticles for highly effective photoacoustic image guided chemo-photothermal synergistic therapy.

Multifunctional drug delivery nanoplatform (PDPP3T@PSNiAA NPs) based on NIR absorbing semiconducting polymer nanoparticles for pH/NIR light-controllably regulated drug release has been successfully prepared. In this strategy, pH/thermal-sensitive multifunctional polymer polystyrene-b-poly(N-isopropylacrylamide-co-acrylic acid) (PSNiAA) was meticulously designed and synthesized using the reversible addition fragmentation chain transfer (RAFT) polymerization method. Furthermore, PSNiAA was used to functionalize diketopyrrolopyrrole-based semiconducting polymer (PDPP3T) to combine photothermal capacity and pH/thermo-responsive drug release in one entity. The prepared PDPP3T@PSNiAA NPs exhibited high photothermal conversion efficiency (η = 34.1%) and excellent photoacoustic (PA) brightness. Meanwhile, benefiting from the photothermal effect of PDPP3T and the pH/thermal-responsive properties of PSNiAA, Dox-loaded PDPP3T@PSNiAA NPs (PDPP3T@PSNiAA-Dox NPs) were able to controllably regulate the release of Dox by pH/NIR light, in which the enhanced drug release at acidic condition upon NIR irradiation phenomenon would minimize unnecessary drug release in normal tissues and was highly beneficial for precise synergistic chemo- and photothermal therapy.

Two-photon semiconducting polymer nanoparticles as a new platform for imaging of intracellular pH variation.

Intracellular pH (pHi) plays a crucial role in cell physiological and pathological processes. We herein report an efficient pH-sensitive sensor based on two-photon excitable semiconducting polymer nanoparticles (PFV/PSMA-DA NPs) for pHi sensing. PFV/PSMA NPs were functionalized with redox-active dopamine (DA) and the obtained PFV/PSMA-DA NPs showed sensitive and reversible pH response over the pH range of 5.0-9.0. Owning to the high biocompatibility and pH-responsive DA, PFV/PSMA-DA NPs show low cytotoxicity and the quantification and imaging of intracellular pH changes of HeLa cells were successfully realized. Moreover, the detection of intracellular pH fluctuation induced by redox species such as NAC (N-acetylcysteine) and H2O2 was also achieved by both one- and two-photon excitation of the PFV/PSMA-DA NPs probe. This work clearly shows that nanoprobe based on two-photon PFV/PSMA-DA NPs could serve as a promising platform for quantitatively monitoring the intracellular pH fluctuations.

Highly Stable Core-Shell Structured Semiconducting Polymer Nanoparticles for FRET-Based Intracellular pH Imaging.

Highly stable semiconducting polymer nanoparticles (NPs) (poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO)/ poly(fluorene-2,7-ylenevinylene-co-phenylene) (PFV)-dopamine (DA) NPs) with previously unreported core-shell structure are developed for ratiometric sensing of intracellular pH values. PFO/PFV-DA NPs comprise central polyfluorene (PFO) as donor and PFV as acceptor, in which the donor and acceptor are spatially separated into the central core and nanoparticle shell. Specifically, thick PFV shells can not only significantly minimize the quenching interference of dopamine on the emission of standard reference (PFO), but are also able to maximize its accessibility to pH-sensitive dopamine and lead to sensitive response to pH changes. The resulting core-shell PFO/PFV NPs are structurally and optically stable, which can avoid the photobleaching and leakage of materials issues compared to traditional semiconducting polymer nanoparticles (SPNs)-based fluorescence resonance energy transfer (FRET) systems containing small molecules. Additionally, the designed compact PFO/PFV-DA NPs show quantitative response to the pH values in aqueous media and are capable of mapping intracellular pH fluctuations by ratiometric imaging. This work may open up opportunities for the generalizability of the consistent ratiometric emission intensity strategy based on core-shell structured SPNs nanoprobes for highly sensitive biological sensing.

Mussel-inspired functionalization of semiconducting polymer nanoparticles for amplified photoacoustic imaging and photothermal therapy.

A versatile and straightforward strategy for the encapsulation of semiconducting polymer nanoparticles (SPNs) using biocompatible polydopamine (PDA) as both the protection and versatile bioconjugation layer is proposed. In addition to providing stable functionalized SPNs, this approach provides SPNs with a flexible surface for further modification with various functional ligands. In this study, three representative surface modifiers including a small molecule (folic acid, FA), a peptide (cRGD) and a stealth polymer (SH-PEG) were conjugated onto the surface of SPNs. Specifically, PDA encapsulation can reliably form SPNs that are uniform in size (∼65 nm) and facilitate the rapid purification of SPN bioconjugates by centrifugation which is difficult to achieve using traditional methods for preparing SPN bioconjugates. Compared to pristine PSBTBT NPs, the synthesized PSBTBT@PDA NPs simultaneously showed more excellent structural stability, significantly enhanced PA brightness and amplified PTT efficacy. Benefiting from the outstanding PA and PTT performances, it is possible for the PSBTBT@PDA NPs to ablate tumors more effectively compared to PSBTBT NPs. Our study thus demonstrates that the PDA encapsulated SPNs should be a promising theranostic agent for PA imaging and PTT.

Polyhedral Oligomeric Silsesquioxane (POSS)-Based Cationic Conjugated Oligoelectrolyte/Porphyrin for Efficient Energy Transfer and Multiamplified Antimicrobial Activity.

Cationic quaternary ammonium (QA) groups and reactive oxygen species as two main approaches for antibacterial study have been intensively studied. Herein, we report a multifunctional antimicrobial agent (porphyrin-POSS-OPVE, PPO), which combines bacterial membrane intercalation, high density of local QA groups, efficient energy transfer, significantly reduced aggregation, and high water solubility into one single molecule. The light-harvesting PPO contains multiple donor-absorbing arms (oligo( p-phenylenevinylene) electrolytes, OPVEs) on its globular periphery and a central porphyrin acceptor in the core by using three-dimensional nanocages (polyhedral oligomeric silsesquioxanes, POSSs) as bridges. The antiaggregation ability of POSS and the highly efficient energy transfer from multiple OPVE arms to porphyrin could greatly amplify singlet oxygen generation in PPO. Particularly, OPVEs with QA terminal chains were able to intercalate into Escherichia coli membranes, which facilitated 1O2 diffusion and bacterial cell membrane disintegration by QA groups. The increased local cationic QA charges in OPVE arms can also enhance the biocidal activity of PPO. Benefiting from these satisfactory features, PPO exhibits multiamplified antibacterial efficacy under a very low concentration level and white light dose (400-700 nm, 6 mW·cm-2, 5 min, 1.8 J·cm-2) to Escherichia coli (8 µM) and Staphylococcus aureus (500 nM). Therefore, PPO shows great potential for photodynamic antimicrobial chemotherapy at a much lower irradiation light dose and photosensitizer concentration level compared to previous reports.

Nanoscale Organic-Inorganic Hybrid Photosensitizers for Highly Effective Photodynamic Cancer Therapy.

Recently, photodynamic therapy (PDT) has attracted significant attention as a minimally invasive approach for cancer treatment. Clinical applications of current photosensitizers are often limited by their poor water solubility, low singlet oxygen (1O2) quantum yields, long-term toxicity, instability, and complex nanostructures. Here, we report a rational design of polyhedral oligomeric silsesquioxanes (POSSs)-based porphyrin (PPP5000) used as an intrinsically nanoscale photosensitizer. In this strategy, inorganic 3D rigid block POSSs not only act as antiaggregate units but also provide conjugating reactive sites for further chemical modification. Without an additional carrier and formulation process, PPP5000 intrinsically shows high water solubility (∼40 mg/mL), good PDT efficiency, and more excellent anticancer performance compared to tetra(hydroxyphenyl)porphyrin (the parent compound of m-THPC, Foscan). Considering the organic nature of porphyrin and the biodegradable property of inorganic POSS scaffolds at physiological conditions, the present work may lead to a new generation of biodegradable and intrinsic PDT agents with overall performance superior to conventional agents in terms of 1O2 production efficiency, water solubility, structurally stability, photostability, and biocompatibility.

Rapid aptasensor capable of simply detect tumor markers based on conjugated polyelectrolytes.

In this paper, a very simple, easily-operated and universal platform is proposed for tumor marker detection. In this strategy, tumor marker-specific aptamer, which can quench the fluorescence of polyfluorene-based cationic conjugated polyelectrolytes (PFN+), are used as recognizing probes. Upon addition of tumor marker, the aptamer can be assembled into the tumor marker-aptamer complex, resulting in fluorescence recovery of PFN+ and the detection of the targets. The most widely-used tumor markers, carcinoembryonic antigen (CEA) and fetoprotein (AFP) have been chosen as the model analytes for this work. The sensing method is capable of rapidly detect target protein within 5 min without complex handling procedure and expensive instruments. Compared with previous studies, the assay presented here is really simple and avoids either conjugated polyelectrolytes (CPEs) modification or oligonucleotide labeling. This method also shows a wide detection range of 3 orders of magnitude and the detection limit is 0.316 ng/mL for CEA and 1.76 ng/mL for AFP. Furthermore, the approach requires only a convenient"mix-and-detect" procedure and offers a universal platform for the sensitive detection of any target molecule of choice according to the selected aptamer.

A Conjugated Polyelectrolyte with Pendant High Dense Short-Alkyl-Chain-Bridged Cationic Ions: Analyte-Induced Light-Up and Label-Free Fluorescent Sensing of Tumor Markers.

A novel cationic water-soluble conjugated polyelectrolyte (CPE) of polyfluorene that contains 15% fraction of 2,1,3-benzothiadiazole (BT) units (PFC3NBT) has been obtained. PFC3NBT demonstrates intramolecular energy transfer from the fluorene segments to BT sites when negatively charged species (SDS or DNAs) are added, following by a shift in emission color from blue to green, has been developed. The high density of positive charges and pendent short alkyl chains of N-propyltrimethylammoniums endow PFC3NBT with high solubility and high fluorescence quantum efficiency of 33.6% in water. The fluorescence emission properties were investigated in the presence of adverse buffer solutions, different surfactants and DNA strands. Interesting fluorescence emission quenching at short wavelength and fluorescence resonance energy transfer (FRET) induced light-on at BT sites were observed and discussed in detail. Very different from previous reports, the fluorescence emission spectra transition happens with an enhancement of integrated fluorescent intensity. The analytes induced a light-up sensing system was studied with a PFC3NBT/SDS complex mode and confirmed with DNA/DNA-FAM sensing systems. More exciting preliminary results on label-free sensing of tumor markers were also reported by investigating the unique fluorescence response to 11 kinds of proteins. These results provide a new insight view for designing CPEs with light-up and label-free features for biomolecular sensing.

Conjugated Polymer Nanoparticles for Label-Free and Bioconjugate-Recognized DNA Sensing in Serum.

Hybridbio/-synthetic sensory conjugated polymer nanoparticles (CPNs) are developed for selective label-free detection of target ssDNA in serum. Carboxylic acid-functionalized anionic polyfluorene nanoparticles are rationally designed as signal amplifying unit to bioconjugate with amine functionalized single stranded oligonucleotides as a receptor. The covalent DNA coating can significantly improve the photostability of the DNA-bioconjugated CPNs over a wide range of buffer conditions. Better ssDNA discrimination for the DNA-bioconjugated CPNs sensor is achieved owing to increased interchain interactions and more efficient exciton transport in nanoparticles. The distinguishable fluorescent color for DNA-bioconjugated CPNs in the presence of target ssDNA allows naked-eye detection of ssDNA under UV irradiation.

Chemically Functionalized Conjugated Oligoelectrolyte Nanoparticles for Enhancement of Current Generation in Microbial Fuel Cells.

Water-soluble conjugated oligoelectrolyte nanoparticles (COE NPs), consisting of a cage-like polyhedral oligomeric silsesquioxanes (POSS) core equipped at each end with pendant groups (oligo(p-phenylenevinylene) electrolyte, OPVE), have been designed and demonstrated as an efficient strategy in increasing the current generation in Escherichia coli microbial fuel cells (MFCs). The as-prepared COE NPs take advantage of the structure of POSS and the optical properties of the pendant groups, OPVE. Confocal laser scanning microscopy showed strong photoluminescence of the stained cells, indicating spontaneous accumulation of COE NPs within cell membranes. Moreover, the electrochemical performance of the COE NPs is superior to that of an established membrane intercommunicating COE, DSSN+ in increasing current generation, suggesting that these COE NPs thus hold great potential to boost the performance of MFCs.

Facile preparation of multicolor polymer nanoparticle bioconjugates with specific biorecognition.

A facile and efficient strategy to prepare multicolor and surface-functionalizable conjugated polymer nanoparticles (PPVseg-COOH CPNs) was demonstrated. The CPNs with tunable photoluminescence colors and carboxylate groups were further covalently modified with a series of specific molecules such as streptavidin, IgG and poly(ethylene glycol) to show their generality for subsequent bioconjugation and biological applications. The streptavidin coating can significantly improve the photostability of the PPVseg-SA CPNs, which indicates that specific biomolecules such as streptavidin functionalization of multicolor PPVseg-COOH CPNs can be applied to achieve high optical stability of CPNs in various buffer solutions, metal ions for many biological applications. Furthermore, the resulted PPVseg-SA CPNs also show efficient labeling ability in specific cellular imaging. The synthetic methods present the feasibility and versatility for further developing surface-functionalizable CPNs probes with full-color tunability for biological imaging and bioanalytical applications.

General synthesis of noble metal (Au, Ag, Pd, Pt) nanocrystal modified MoS2 nanosheets and the enhanced catalytic activity of Pd-MoS2 for methanol oxidation.

A general and facile method for water-dispersed noble metal (Au, Ag, Pd, Pt) nanocrystal modified MoS2 nanosheets (NM-MoS2 NSs) has been developed. By using sodium carboxymethyl cellulose as a stabilizer, well-dispersed NM-MoS2 NSs with homogeneously deposited noble metal nanocrystals (NM NCs) can be synthesized in aqueous solutions. Due to the transition from the semiconducting 2H phase to the metallic 1T phase, the chemically exfoliated MoS2 (ce-MoS2) NSs have improved electrochemical activity. The partially metallic nature of the ce-MoS2 NSs and the catalytic activity of the NM NCs synergistically make NM-MoS2 NSs a potential electrochemical catalyst. For the first time, Pd-MoS2 NSs were used as an electrocatalyst for methanol oxidation in alkaline media. The results showed that Pd-MoS2 NSs have enhanced catalytic activity with 2.8-fold anodic peak current mass density compared to a commercial Pd/C catalyst, suggesting potential for application in direct methanol fuel cells (DMFCs).

A controllable approach to development of multi-spectral conjugated polymer nanoparticles with increased emission for cell imaging.

The authors demonstrate a smart and versatile approach for preparing multi-spectral conjugated polymers from a commercial precursor MEH-PPV without tedious synthetic modification. Multi-color CPNs with small size have also been successfully prepared using a modified-reprecipitation procedure for live cell imaging.