Conjugated Polymer Nanoparticles Research Articles

Enhanced inactivation of Staphylococcus aureus and Escherichia coli using conjugated polyindole polymer nanoparticles under visible light irradiation

AbstractThe areas of environmental cleanup and bacteria inactivation are particularly interesting in polymer‐based nanomaterials because of their unique physicochemical properties. Conjugated polymer nanoparticles (CP NPs) have potential uses in the biological and environmental, but little is known about them. This study aimed to examine the efficacy of CP nanoparticles in the photocatalytic inactivation of S. aureus and E. coli under visible irradiation (λ ≤ 420 nm), with minor enhancements observed. The simple and one‐step chemical oxidation technique was used to prepare CP nanoparticles. X‐ray powder diffraction (XRD), Fourier‐transform infrared spectroscopy (FT‐IR), Scanning electron microscope (SEM), Energy‐dispersive X‐ray (EDS), and Transmission electron microscopy (TEM) analyses were utilized to characterize the physicochemical properties of CP nanoparticles for comprehensive structural analysis. The synthesized CP nanoparticles exhibited outstanding photocatalytic disinfection capabilities, achieving a degradation of 98.6%. This research not only provides insights into the physical characteristics of CP nanoparticles but also illustrates their antibacterial efficacy against two different bacterial pathogens, namely S. aureus and E. coli. Therefore, this research highlights an eco‐friendly and inexpensive preparation of conjugated polymer nanoparticles for a wide range of applications.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Microenvironment with NIR-Controlled ROS and Mechanical Tensions for Manipulating Cell Activities in Wound Healing.

The extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell-material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge. Here, near-infrared (NIR)-controlled multifunctional hydrogel platforms, named PIC/CM@NPs, are introduced to dictate fibroblast behavior during wound healing by tuning the matrix oxidative stress and mechanical tensions. PIC/CM@NPs are prepared through cell adhesion-medicated assembly of collagen-like polyisocyanide (PIC) polymers and cell-membrane-coated conjugated polymer nanoparticles (CM@NPs), which closely mimic the fibrous structure and nonlinear mechanics of ECM. Upon NIR stimulation, PIC/CM@NPs composites enhance fibroblast cell proliferation, migration, cytokine production, and myofibroblast activation, crucial for wound closure. Moreover, they exhibit effective and toxin removal antibacterial properties, reducing inflammation. This multifunctional approach accelerates healing by 95%, highlighting the importance of integrating biochemical and biophysical cues in the biomaterial design for advanced tissue regeneration.

Chemiluminescent Conjugated Polymer Nanoparticles for Deep-Tissue Inflammation Imaging and Photodynamic Therapy of Cancer.

Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases.

DNA‐Mediated, On‐Membrane Sequential Assembly of Conjugated Polymer Nanoparticles for Sensitive Detection of Cell Surface Markers

AbstractFlow cytometry can provide detailed information about protein expression on cell surface and is, therefore, widely used in clinical testing. However, owing to the limited sensitivity of fluorescence signals, detection of low‐expression cell surface markers is challenging. The present report describes a DNA‐mediated, on‐membrane assembly of conjugated polymer nanoparticles (Pdots) that amplifies fluorescence signal from surface markers for sensitive detection via flow cytometry. Single‐stranded DNA (ssDNA)‐conjugated antibodies are first bound to cell surface markers, from which ssDNA‐modified Pdots are sequentially assembled using DNA hybridization. The use of DNA as a linker enables the distance‐controlled assembly of Pdots to prevent fluorescence quenching, whereas their on‐membrane sequential assembly allows amplification of the fluorescence signal without reducing binding ability of antibodies. Thus, two rounds of Pdot assembly achieve 31‐fold amplification of the fluorescence signal from CD19 on Nalm‐6 cells, which is 125‐fold brighter than that obtained using the conventional fluorescent dye‐based method. Moreover, the sequential assembly of 22 nm Pdots shows 24‐fold higher fluorescence than one‐step labeling with 81 nm Pdots, suggesting the advantage of the sequential assembly strategy in avoiding steric hindrance. The proposed method is expected to contribute to the sensitive detection of low‐expression surface markers for early and accurate diagnosis.

Size Modulation of Conjugated Polymer Nanoparticles for Improved NIR-II Fluorescence Imaging and Photothermal Therapy.

Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light-heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.

Selective photothermal and photodynamic capabilities of conjugated polymer nanoparticles

We found out that the conjugated polymers with different molecular weights and fullerene addition selectively controlled the photothermal and photodynamic effects of conjugated polymer nanoparticles (CPNs). It turned out that the use of high molecular weight (MW) conjugated polymer increase near infrared absorption, resulting in more photothermal effect than photodynamic effect. The highest photothermal effect was achieved when the more molecular ordering was expected by using a high MW conjugated polymer, phase-separated film dispersion process and a phospholipid-polyethylene glycol with alkyl tails for dense association with alkyl side chains of a conjugated polymer. On the other hand, the photodynamic effect was generally enhanced when less-organized molecular assemblies were expected by using a low MW conjugated polymer, a nanoprecipitation process, and/or a surfactant without compact alkyl chain association with a conjugated polymer. It was notable that fullerene acted differently on the photophysical properties of CPNs, depending on the molecular ordering. With limited fluctuation in the photothermal effect, the fullerene addition into CPNs enhanced the photodynamic effect under situations that can disrupt molecular ordering. In the meantime, the fullerene in CPNs enhanced the photothermal effect while maintaining the photodynamic effect with higher molecular ordering. Our results show that the combination of fullerenes can selectively and significantly increase the phototherapeutic capabilities based on molecular ordering of CPNs, suggesting a strategic approach for efficiency enhancement in the phototherapeutic medicinal applications.

A comprehensive review on singlet oxygen generation in nanomaterials and conjugated polymers for photodynamic therapy in the treatment of cancer.

A key role in lessening humanity's continuous fight against cancer could be played by photodynamic therapy (PDT), a minimally invasive treatment employed in the medical care of a range of benign disorders and malignancies. Cancerous tissue can be effectively removed by using a light source-excited photosensitizer. Singlet oxygen and reactive oxygen species are produced via the photosensitizer as a result of this excitation. In the recent past, researchers have put in tremendous efforts towards developing photosensitizer molecules for photodynamic treatment (PDT) to treat cancer. Conjugated polymers, characterized by their efficient fluorescence, exceptional photostability, and strong light absorption, are currently under scrutiny for their potential applications in cancer detection and treatment through photodynamic and photothermal therapy. Researchers are exploring the versatility of these polymers, utilizing sophisticated chemical synthesis and adaptable polymer structures to create new variants with enhanced capabilities for generating singlet oxygen in photodynamic treatment (PDT). The incorporation of photosensitizers into conjugated polymer nanoparticles has proved to be beneficial, as it improves singlet oxygen formation through effective energy transfer. The evolution of nanotechnology has emerged as an alternative avenue for enhancing the performance of current photosensitizers and overcoming significant challenges in cancer PDT. Various materials, including biocompatible metals, polymers, carbon, silicon, and semiconductor-based nanomaterials, have undergone thorough investigation as potential photosensitizers for cancer PDT. This paper outlines the recent advances in singlet oxygen generation by investigators using an array of materials, including graphene quantum dots (GQDs), gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), titanium dioxide (TiO2), ytterbium (Yb) and thulium (Tm) co-doped upconversion nanoparticle cores (Yb/Tm-co-doped UCNP cores), bismuth oxychloride nanoplates and nanosheets (BiOCl nanoplates and nanosheets), and others. It also stresses the synthesis and application of systems such as amphiphilic block copolymer functionalized with folic acid (FA), polyethylene glycol (PEG), poly(β-benzyl-L-aspartate) (PBLA10) (FA-PEG-PBLA10) functionalized with folic acid, tetra(4-hydroxyphenyl)porphyrin (THPP-(PNIPAM-b-PMAGA)4), pyrazoline-fused axial silicon phthalocyanine (HY-SiPc), phthalocyanines (HY-ZnPcp, HY-ZnPcnp, and HY-SiPc), silver nanoparticles coated with polyaniline (Ag@PANI), doxorubicin (DOX) and infrared (IR)-responsive poly(2-ethyl-2-oxazoline) (PEtOx) (DOX/PEtOx-IR NPs), particularly in NIR imaging-guided photodynamic therapy (fluorescent and photoacoustic). The study puts forward a comprehensive summary and a convincing justification for the usage of the above-mentioned materials in cancer PDT.

Advancements in conjugated polymer research: applications in organic photovoltaics and field effect transistors

This review provides a comprehensive overview of the development and applications of conjugated polymer semiconductors. The review summarizes the current state of research in this field, including the synthesis and characterization of these materials, their properties, and potential applications. The scope covers a wide range of topics, including organic photovoltaics, organic field-effect transistors, and conjugated polymer nanoparticles. The main findings highlight the significant progress that has been made in this field, with conjugated polymers exhibiting favorable electronic and optical properties, as well as high charge mobility. These materials have shown great potential for use in various applications, including solar cells, light-emitting diodes, and field-effect transistors. The applications are far-reaching, with the potential to revolutionize the electronics industry by providing low-cost, flexible, and environmentally friendly alternatives to traditional inorganic materials. One of the key challenges facing this field is the need to improve the efficiency and stability of conjugated polymer-based devices. While significant progress has been made in this area, there is still much work to be done to develop materials and device architectures that can achieve high performance over extended periods of time. Another challenge is the need to develop scalable manufacturing processes that can produce large quantities of high-quality conjugated polymers at a reasonable cost. The continued advancement of this field holds great promise for the development of new technologies that can improve our lives and help to address some of the world’s most pressing challenges.

The light-dependent pseudo-capacitive charging of conjugated polymer nanoparticles coupled with the depolarization of the neuronal membrane.

The mechanism underlying visual restoration in blind animal models of retinitis pigmentosa using a liquid retina prosthesis based on semiconductive polymeric nanoparticles is still being debated. Through the application of mathematical models and specific experiments, we developed a coherent understanding of abiotic/biotic coupling, capturing the essential mechanism of photostimulation responsible for nanoparticle-induced retina activation. Our modeling is based on the solution of drift-diffusion and Poisson-Nernst-Planck models in the multi-physics neuron-cleft-nanoparticle-extracellular space domain, accounting for the electro-chemical motion of all the relevant species following photoexcitation. Modeling was coupled with electron microscopy to estimate the size of the neuron-nanoparticle cleft and electrophysiology on retina explants acutely or chronically injected with nanoparticles. Overall, we present a consistent picture of electrostatic depolarization of the bipolar cell driven by the pseudo-capacitive charging of the nanoparticle. We demonstrate that the highly resistive cleft composition, due to filling by adhesion/extracellular matrix proteins, is a crucial ingredient for establishing functional electrostatic coupling. Additionally, we show that the photo-chemical generation of reactive oxygen species (ROS) becomes relevant only at very high light intensities, far exceeding the physiological ones, in agreement with the lack of phototoxicity shown in vivo.

Conjugated Polymer Nanoparticles as Visible Light Panchromatic Photoinitiators for 3D Printing of Acrylic Hydrogels

Conjugated Polymer Nanoparticles as Visible Light Panchromatic Photoinitiators for 3D Printing of Acrylic Hydrogels

Current and Potential Roles of Ferroptosis in Bladder Cancer.

Ferroptosis, a type of regulated cell death driven by iron-dependent lipid peroxidation, is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species. Ferroptosis is a prevalent and primitive form of cell death. Numerous cellular metabolic processes regulate ferroptosis, including redox homeostasis, iron regulation, mitochondrial activity, amino acid metabolism, lipid metabolism, and various disease-related signaling pathways. Ferroptosis plays a pivotal role in cancer therapy, particularly in the eradication of aggressive malignancies resistant to conventional treatments. Multiple studies have explored the connection between ferroptosis and bladder cancer, focusing on its incidence and treatment outcomes. Several biomolecules and tumor-associated signaling pathways, such as p53, heat shock protein 1, nuclear receptor coactivator 4, RAS-RAF-MEK, phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin, and the Hippo-tafazzin signaling system, exert a moderating influence on ferroptosis in bladder cancer. Ferroptosis inducers, including erastin, artemisinin, conjugated polymer nanoparticles, and quinazolinyl-arylurea derivatives, hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment. Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer. In this review, we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

Conjugated Polymer Composite Nanoparticles Augmenting Photosynthesis-Based Light-Triggered Hydrogel Promotes Chronic Wound Healing.

Diabetic chronic wounds are characterized by local hypoxia, impaired angiogenesis, and bacterial infection. In situ, self-supply of dissolved oxygen combined with the elimination of bacteria is urgent and challenging for chronic nonhealing wound treatment. Herein, an oxygen-generating system named HA-L-NB/PFE@cp involving biological photosynthetic chloroplasts (cp)/conjugated polymer composite nanoparticles (PFE-1-NPs@cp) and light-triggered hyaluronic acid-based (HA-L-NB) hydrogel for promoting diabetic wound healing is introduced. Briefly, conjugated polymer nanoparticles (PFE-1-NPs) possess unique light harvesting ability, which accelerates the electron transport rates in photosystem II (PS II) by energy transfer, elevating photosynthesis beyond natural chloroplasts. The enhanced release of oxygen can greatly relieve hypoxia, promote cell migration, and favor antibacterial photodynamic therapy. Additionally, the injectable hydrogel precursors are employed as a carrier to deliver PFE-1-NPs@cp into the wound. Under light irradiation, they quickly form a gel by S-nitrosylation coupling reaction and in situ anchor on tissues through amine-aldehyde condensation. Both in vitro and in vivo assays demonstrate that the oxygen-generating system can simultaneously relieve wound hypoxia, eliminate bacteria, and promote cell migration, leading to the acceleration of wound healing. This study provides a facile approach to develop an enhanced oxygen self-sufficient system for promoting hypoxic tissue, especially diabetic wound healing.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Conjugated polymer nanoparticles as sonosensitizers in sono-inactivation of a broad spectrum of pathogens

Sonodynamic inactivation (SDI) of pathogens has an important advantage when compared to optical excitation-based protocols due to the deeper penetration of ultrasound (US) excitation in biological media or animal tissue. Sonosensitizers (SS) are compounds or systems that upon US stimulation in the therapeutic window (frequency = 0.8–3 MHz and intensity < 3 W/cm2) can induce damage to vital components of pathogenic microorganisms. Herein, we report the synthesis and application of conjugated polymer nanoparticles (CPNs) as an efficient SS in SDI of methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Candida tropicalis. A frequent problem in the design and testing of new SS for SDI is the lack of proper sonoreactor characterization which leads to reproducibility concerns. To address this issue, we performed dosimetry experiments in our setup. This enables the validation of our results by other researchers and facilitates meaningful comparisons with different SDI systems in future studies. On a different note, it is generally accepted that the mechanisms of action underlying SS-mediated SDI involve the production of reactive oxygen species (ROS). In an attempt to establish the nature of the cytotoxic species involved in our CPNs-based SDI protocol, we demonstrated that singlet oxygen (1O2) does not play a major role in the observed sonoinduced killing effect. SDI experiments in planktonic cultures of optimally growing pathogens using CPNs result in a germicide effect on the studied pathogenic microorganisms. The implementation of SDI protocols using CPNs was further tested in mature biofilms of a MRSA resulting in ∼40 % reduction of biomass and ∼70 % reduction of cellular viability. Overall, these results highlight the unique and unexplored capacity of CPNs to act as sonosensitizers opening new possibilities in the design and application of novel inactivation protocols against morbific microbes.

Tetraphenylethene-Based Cross-Linked Conjugated Polymer Nanoparticles for Efficient Detection of 2,4,6-Trinitrophenol in Aqueous Phase.

The cross-linked conjugated polymer poly(tetraphenylethene-co-biphenyl) (PTPEBP) nanoparticles were prepared by Suzuki-miniemulsion polymerization. The structure, morphology, and pore characteristics of PTPEBP nanoparticles were characterized by FTIR, NMR, SEM, and nitrogen adsorption and desorption measurements. PTPEBP presents a spherical nanoparticle morphology with a particle size of 56 nm; the specific surface area is 69.1 m2/g, and the distribution of the pore size is centered at about 2.5 nm. Due to the introduction of the tetraphenylethene unit, the fluorescence quantum yield of the PTPEBP nanoparticles reaches 8.14% in aqueous dispersion. Combining the porosity and nanoparticle morphology, the fluorescence sensing detection toward nitroaromatic explosives in the pure aqueous phase has been realized. The Stern-Volmer quenching constant for 2,4,6-trinitrophenol (TNP) detection is 2.50 × 104 M-1, the limit of detection is 1.07 μM, and the limit of quantification is 3.57 μM. Importantly, the detection effect of PTPEBP nanoparticles toward TNP did not change significantly after adding other nitroaromatic compounds, indicating that the anti-interference and selectivity for TNP detection in aqueous media is remarkable. In addition, the spike recovery test demonstrates the potential of PTPEBP nanoparticles for detecting TNP in natural environmental water samples.

Positively Charged Semiconductor Conjugated Polymer Nanomaterials with Photothermal Activity for Antibacterial and Antibiofilm Activities In Vitro and In Vivo.

Biofilm infections are associated with most human bacterial infections and are prone to bacterial multidrug resistance. There is an urgent need to develop an alternative approach to antibacterial and antibiofilm agents. Herein, two positively charged semiconductor conjugated polymer nanoparticles (SPPD and SPND) were prepared for additive antibacterial and antibiofilm activities with the aid of positive charge and photothermal therapy (PTT). The positive charge of SPPD and SPND was helpful in adhering to the surface of bacteria. With an 808 nm laser irradiation, the photothermal activity of SPPD and SPND could be effectively transferred to bacteria and biofilms. Under the additive effect of positive charge and PTT, the inhibition rate of Staphylococcus aureus (S. aureus) treated with SPPD and SPND (40 μg/mL) could reach more than 99.2%, and the antibacterial activities of SPPD and SPND against S. aureus biofilms were 93.5 and 95.8%. SPPD presented better biocompatibility than SPND and exhibited good antibiofilm properties in biofilm-infected mice. Overall, this additive treatment strategy of positive charge and PTT provided an optional approach to combat biofilms.

Novel Application of NIR-I-Absorbing Quinoidal Conjugated Polymer as a Photothermal Therapeutic Agent.

Conjugated polymer nanoparticles (CP NPs) that could absorb the first near-infrared (NIR-I) window have emerged as highly desirable therapeutic nanomaterials. Here, a quinoidal-conjugated polymer (QCP), termed PQ, was developed as a novel class of therapeutic agents for photothermal therapy (PTT). Owing to its intrinsic quinoid structure, PQ exhibits molecular planarity and π-electron overlap along the conjugated backbone, endowing it with a narrow band gap, NIR-I absorption, and diradical features. The obtained PQ was coated with a poly(ethylene glycol) (PEG) moiety, affording nanosized and water-dispersed PQ nanoparticles (PQ NPs), which consequently show a high photothermal conversion efficiency (PCE) of 63.2%, good photostability, and apparent therapeutic efficacy for both in vitro and in vivo PTTs under an 808 nm laser irradiation. This study demonstrates that QCPs are promising active agents for noninvasive anticancer therapy using NIR-I light.

Structural design of conjugated polymers for fluorescence bioimaging in the second near‐infrared window

AbstractFluorescence imaging in the second near‐infrared (NIR‐II) region has become one of the most powerful tools in clinical diagnosis and therapy assessment because of its high spatial resolution, rapid feedback, radiation safety, and low cost. Conjugated polymer nanoparticles (Pdots) based on donor‐acceptor (D‐A) polymers are some of the most promising fluorescent probes which have many superior characteristics, such as a high fluorescence brightness, good photostability, facile functionalization, and low cytotoxicity. While there has been tremendous progress in developing fluorescent polymers for use in the NIR‐II wavelength range, the types of monomer structures used as building blocks for NIR‐II fluorophores are still limited compared to those for organic solar cells and organic transistors. This review summarizes the NIR‐II fluorescent polymers reported in the past few decades. The donor/acceptor unit structures of the polymers are systematically classified and discussed, which will provide new insights into the logical molecular design of donor/acceptor units for the development of high‐brightness NIR‐II Pdots.

EXPLORING THE INTERPLAY BETWEEN BRAIN TUMOUR INITIATING CELLS AND THE TUMOUR MICROENVIRONMENT: POTENTIAL TARGETING STRATEGIES FOR GLIOBLASTOMA

Abstract The aggressive biology and poor response to therapy resulting in relapse of patients with GBM is attributed to the existence of Brain Tumour Initiating Cells (BTICs) with stem cell properties. Targeting BTICs in isolation of their surrounding tumour microenvironment (TME) has proven ineffective. Determining the molecular effects of the TME on BTICs is an evolving area that requires more focus. OUR APPROACH: Using innovative patient-derived organoid co-culture models paired with an in vivo zebrafish xenograft system our multidisciplinary team is exploring the biology of BTICs in the context of their microenvironment in search for novel therapeutic options that will benefit GBM patients. RESULTS: Our data supports an important role for activated cancer associated fibroblasts and endothelial cells in driving BTIC expansion and resistance to therapy. We further show that these effects, at least in part, are attributed to changes in the composition of the TME. Using semi-conducting conjugated polymer nanoparticles designed to selectively disrupt microenvironment interactions with BTICs, we show a reduction in anti-apoptotic and proliferation markers and a decreased self-renewal in functional assays. In vitro and in vivo drug response assays reveal this combined approach sensitizes to standard of care Temozolomide. CONCLUSIONS: Our data reveals novel aspects of the TME that play an essential role in the biology of GBM and in resistance to therapy. We propose that this offers unique opportunities for drug targeting that may improve patient outcomes for this aggressive disease.