Molecular Oligomerization and Donor Engineering Strategies for Achieving Superior NIR-II Fluorescence Imaging and Thermotherapy under 1064 nm Laser Irradiation.

An enormous challenge still exists for designing molecules with the second near-infrared (NIR-II, 1000-1700 nm) window absorption, NIR-II fluorescence emission, and batch-to-batch reproducibility, which is the premise for high-performance NIR-II phototheranostics. Although organic small molecules and polymers have been largely explored for phototheranostics, it is difficult to satisfy the above three elements simultaneously. In this work, molecular oligomerization (the general structure is S-D-A-D'-A-D-S) and donor engineering (changing the donor linker D') strategies are applied to design phototheranostic agents. Such strategies are proved to be efficient in adjusting molecular configuration and energy level, affecting the optical and thermal properties. Three oligomers (O-T, O-DT, and O-Q) are further prepared into water-soluble nanoparticles (NPs). Particularly, the O-T NPs exhibit a higher molar extinction coefficient at 1064 nm (≈4.3-fold of O-DT NPs and ≈4.8-fold of O-Q NPs). Furthermore, the O-T NPs show the highest NIR-II fluorescence brightness and heating capacity (PCE = 73%) among the three NPs under 1064 nm laser irradiation and served as agents for NIR-II imaging guided in vivo photothermal therapy. Overall, by using molecular oligomerization and donor engineering strategies, a powerful example of constructing high-performance NIR-II phototheranostics for clinical translation is given.

An Activatable Phototheranostic Nanoplatform for Tumor Specific NIR-II Fluorescence Imaging and Synergistic NIR-II Photothermal-Chemodynamic Therapy.

The phototheranostics in the second near-infrared window (NIR-II) have proven to be promising for the precise cancer theranostics. However, the non-responsive and "always on" imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR-II phototheranostic nanoplatform (Ag2 S-Fe(III)-DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2 S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in "off" state, due to the FRET between Ag2 S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly "turn on" by the overexpressed GSH in tumor tissues, achieving a superior tumor-to-normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti-tumor therapeutic effect. The work provides a promising strategy for the development of TME activated NIR-II phototheranostic nanoprobes.

Increasing Molecular Planarity through Donor/Side-Chain Engineering for Improved NIR-IIa Fluorescence Imaging and NIR-II Photothermal Therapy under 1064†nm.

Developing conjugated small molecules (CSM) with intense NIR-II (1000-1700 nm) absorption for phototheranostic is highly desirable but remains a tremendous challenge due to a lack of reliable design guidelines. This study reports a high-performance NIR-II CSM for phototheranostic by tailoring molecular planarity. A series of CSM show bathochromic absorption extended to the NIR-II region upon the increasing thiophene number, but an excessive number of thiophene results in decreased NIR-IIa (1300-1400 nm) brightness and photothermal effects. Further introduction of terminal nonconjugated alkyl chain can enhance NIR-II absorption coefficient, NIR-IIa brightness, and photothermal effects. Mechanism studies ascribe this overall enhancement to molecular planarity stemming from the collective contribution of donor/side-chain engineering. This finding directs the design of NIR-II CSM by rational manipulating molecular planarity to perform 1064 nm mediated phototheranostic at high efficiency.

NIR-II Excitation Phototheranostic Nanomedicine for Fluorescence/Photoacoustic Tumor Imaging and Targeted Photothermal-Photonic Thermodynamic Therapy.

The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.

Electrochemical Sensing of Exosomal MicroRNA Based on Hybridization Chain Reaction Signal Amplification with Reduced False-Positive Signals.

MicroRNAs (miRNAs) in cancer cell-derived exosomes are important cancer biomarkers. Herein, a sensitive hybridization chain reaction (HCR) electrochemical assay was fabricated for the detection of exosomal microRNA-122 (miR-122). The hairpin DNA (hpDNA) probes were first immobilized on the surface of a gold electrode. In the presence of miR-122, the hairpin structure of the hpDNA could be opened and triggered the HCR through the cross-opening and hybridization of two helper DNA hairpins. Long nicked double helixes generated from HCR are used to capture more RuHex and increase the signal of differential pulse voltammetry (DPV). In this assay, the density of the hpDNA probes on the surface of the gold electrode was precisely controlled by the simultaneous immobilization of hpDNA and short 12 nucleotides single-stranded DNA (S-12), providing a very high amplification efficiency. More importantly, the false positive signal could be reduced or completely eliminated by applying exonuclease I (Exo I) before the introduction of target miR-122. Under optimal conditions, the assay offers very high sensitivity with an attomolar level detection limit, a linear range with 9 orders of magnitude, and specificity in single mismatch discrimination. This sensitive electrochemical assay could successfully evaluate the miR-122 concentration in different cancer-derived exosomes, indicating its potential use in cancer diagnostics.

Highly Sensitive Electrochemical Detection of Tumor Exosomes Based on Aptamer Recognition-Induced Multi-DNA Release and Cyclic Enzymatic Amplification.

Sensitive and specific detection of tumor exosomes is of great significance for early cancer diagnosis. In this paper, we report an aptamer strategy for exosome detection based on aptamer recognition-induced multi-DNA release and cyclic enzymatic amplification. First, we use aptamer-magnetic bead bioconjugates to capture tumor exosomes derived from LNCaP cells, leading to the release of three kinds of messenger DNAs (mDNAs). After magnetic separation, the released mDNAs hybridized with the probe DNAs immobilized on a gold electrode. Electroactive Ru(NH3)63+ was used as the signal reporter because of its electrostatic attraction to DNA. Subsequent Exo III cyclic digestion caused the electrochemical signal to "turn off". Because the electrochemical signal reflects the concentration of Ru(NH3)63+ and the concentration of Ru(NH3)63+ is correlated with the mDNA concentration, which is correlated with the exosome concentration, the tumor exosomes can be detected by examining the decrease in the peak current of Ru(NH3)63+. In this paper, the signal was amplified by the numerous mDNAs released from the magnetic bead and the Exo III-assisted mDNA recycling. Under the optimal conditions, a detection limit down to 70 particles/µL was achieved, which is lower than the LODs of most currently available methods. Furthermore, this assay can be used to detect tumor exosomes in complex biological samples, demonstrating potential application in real sample diagnosis.

"Signal-on" photoelectrochemical biosensor for sensitive detection of human T-Cell lymphotropic virus type II DNA: dual signal amplification strategy integrating enzymatic amplification with terminal deoxynucleotidyl transferase-mediated extension.

A novel "signal-on" photoelectrochemical (PEC) biosensor for sensitive detection of human T-cell lymphotropic virus type II (HTLV-II) DNA was developed on the basis of enzymatic amplification coupled with terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. The intensity of the photocurrent signal was proportional to the concentration of the HTLV-II DNA-target DNA (tDNA) by dual signal amplification. In this protocol, GR-CdS:Mn/ZnS nanocomposites were used as photoelectric conversion material, while pDNA was used as the tDNA recognizing unit. Moreover, the TdT-mediated extension and the enzymatic signal amplification technique were used to enhance the sensitivity of detection. Using this novel dual signal amplification strategy, the prototype of PEC DNA sensor can detect as low as ∼0.033 fM of HTLV-II DNA with a linear range of 0.1-5000 fM, with excellent differentiation ability even for single-base mismatches. This PEC DNA assay opens a promising platform to detect various DNA targets at ultralow levels for early diagnoses of different diseases.

Chronic myeloid leukemia drug evaluation using a multisignal amplified photoelectrochemical sensing platform.

Chronic myeloid leukemia (CML) is a malignant clone disease of hematopoietic stem cells. At present, the most effective therapy for CML is bone marrow transplantation, but this procedure is expensive, and it is often difficult to find appropriately matched bone marrow donors. As an alternative to marrow transplantation, a more effective anticancer drug should be developed to cure the disease; in addition, an effective system to evaluate the activity of the drug needs to be developed. Herein, we present a novel antileukemia drug evaluation method based on a multisignal amplified photoelectrochemical sensing platform that monitors the activity of caspase-3, a known marker of cell apoptosis. Manganese-doped CdS@ZnS core-shell nanoparticles (Mn:CdS@ZnS) were synthesized via a simple wet chemical method, which provided a stable photocurrent signal. A DEVD-biotin peptide and streptavidin-labeled alkaline phosphatise (SA-ALP) were immobilized successively at these nanoparticles through amide bonding and through specific interaction between biotin and streptavidin, respectively. The photocurrent of this sensing platform improved as the ALP hydrolyzed the substrate 2-phospho-l-ascorbic acid (AAP) to ascorbic acid (AA), a more efficient electron donor. The activity of caspase-3 was detected using this sensing platform, and thus, the efficacy of nilotinib for targeting K562 CML cells could be evaluated. The results indicate that nilotinib can effectively induce apoptosis of the K562 cells. This sensing platform exhibited sensitive, reproductive, and stable performance in studying the nilotinib-induced apoptosis of K562 CML cells, and the platform could be utilized to evaluate other anticancer drugs.

ECL cytosensor for sensitive and label-free detection of circulating tumor cells based on hierarchical flower-like gold microstructures.

The development of sensitive and efficient cell sensing strategies to detect circulating tumor cells (CTCs) in peripheral blood is crucial for the early diagnosis and prognostic assessment of cancer clinical treatment. Herein, an array of hierarchical flower-like gold microstructures (HFGMs) with anisotropic nanotips was synthesized by a simple electrodeposition method and used as a capture substrate to construct an ECL cytosensor based on the specific recognition of target cells by aptamers. The complex topography of the HFGMs array not only catalyzed the enhancement of ECL signals, but also induced the cells to generate more filopodia, improving the capture efficiency and shortening the capture time. The effect of topographic roughness on cell growth and adhesion propensity was also investigated, while the cell capture efficiency was proposed to be an important indicator affecting the accuracy of the ECL cytosensor. In addition, the capture of cells on the electrode surface increased the steric hindrance, which caused ECL signal changes in the Ru(bpy)32+ and TPrA system, realizing the quantitative detection of MCF-7 cells. The detection range of the sensor was from 102 to 106 cells mL-1 and the detection limit was 18 cells mL-1. The proposed detection method avoids the process of separation, labeling and counting, which has great potential for sensitive detection in clinical applications.

Anti-Quenching NIR-II Excitation Phenylboronic Acid Modified Conjugated Polyelectrolyte for Intracellular Peroxynitrite-Enhanced Chemo-Photothermal Therapy.

Multidrug resistance to clinical chemotherapeutic drugs severely limits antitumor efficacy and patient survival. The integration of chemotherapy with photothermal therapy (PTT) and reactive nitrogen species has become a major strategy to enhance cancer treatment efficacy. Herein, a multifunctional peroxynitrite (ONOO-) nanogenerator (PBT/NO/Pt) for NIR-II fluorescence (NIR-II FL)/NIR-II photoacoustic (NIR-II PA) imaging-guided chemo/NIR-II PTT/ONOO- combination therapy is reported. The multifunction nanogenerator is developed by co-loading a pH-sensitive nitric oxide donor (DETA NONOate) and nicotinamide adenine dinucleotide phosphate oxidases trigger superoxide (O2 •-) generator chemotherapy drug (CDDP) to an NIR-II excitation-conjugated polyelectrolyte (PNC11BA). PNC11BA has non-conjugated alkyl chain segments in the polymer backbone and abundant positively charged phenylboronic acid in its side chains, which support the anti-quenching of NIR-II FL and the integration of DETA NONOate and CDDP into PBT/NO/Pt. In the acidic tumor microenvironment, the coordination bonds between CDDP and PNC11BA are cleaved, releasing CDDP for chemotherapeutic activity. The simultaneous release of nitric oxide (NO) and O2 •- rapidly leads to the in situ generation of the more cytotoxic reactive physiological nitrogen species ONOO-. In vitro and in vivo results prove that PBT/NO/Pt exhibited a markedly ONOO- enhanced chemo-photothermal synergistic therapy for SKOV3/DDP tumor by downregulating the intracellular glutathione and increasing CDDP-DNA adducts.

Fabrication of conjugated polymers with aggregation-induced near-infrared-II emission for efficient phototheranostics.

Conjugated polymers (CPs), which emit in the second near-infrared window (NIR-II, 1000-1700 nm), are used as biomaterials for NIR-II fluorescence imaging because of their adjustable photophysical properties and high optical stability. However, the fluorescence signal of conventional CPs is quenched in an aggregated state due to strong π-π stacking, which results in the closure of the radiation attenuation pathway. To solve this problem, the aggregation-induced emission effect is considered a reasonable strategy for enhancing the aggregative fluorescence of IR-II emitters. We herein report NIR-II conjugated polymers with typical AIE characteristics (αAIE > 3) by changing the side chain structure of receptor units and the conjugation degree of donors. Conjugated polymer nanoparticles (PoBVT NPs) exhibit outstanding performance in NIR-II fluorescence imaging (QY = 1.94%) and highly effective photothermal therapy (η = 45%). In vivo studies have shown that the location of tumors can be accurately obtained by NIR-II FL/NIR-II PA imaging, and there is a significant anti-tumor effect after laser irradiation. This work offers prospects for the design of multifunctional conjugated polymers for NIR-II FL/PA imaging to guide NIR-II PTT applications.

Dark-field imaging and fluorescence dual-mode detection of microRNA-21 in living cells by core-satellite plasmonic nanoprobes.

The in situ precise quantification and simultaneous imaging of low abundance microRNAs (miRNAs) within living cells is critical for cancer diagnosis, yet it remains a significant challenge. Leveraging the excellent sensitivity and spatiotemporal resolution of dark-field microscopy (DFM) and fluorescence imaging, we have successfully devised a novel detection approach using dual-signal reporter probes (DSRPs). These probes allow for highly sensitive detection of miRNA-21 in living cells via toehold-mediated strand displacement cascades. The DSRPs were constructed by Au nanoparticles and Ag nanoclusters core-satellite nanostructures. After the recognition of miRNA-21, the strand displacement cascades were triggered, inducing the disassembly of the Au/Ag core-satellite nanostructure with apparent scattering intensity decrease and peak wavelength shifts. Additionally, the fluorescence of Ag clusters could be recovered and further enhanced when in close proximity to specific guanine-rich strands. The dual-signal response capability enables the accurate detection of miRNA-21 from 1 fM to 1 nM, with a limit of detection reached 0.75 fM. DFM and fluorescent imaging of living cells efficiently confirms the applicable detection of miRNA-21 in complex detection media. The biosensor based on DSRPs represents a promising nanoplatform for visual monitoring and imaging of biomolecules in living cells, even at the single particle level.

A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

A Mitochondria-Targeted NIR-II Molecule Fluorophore for Precise Cancer Phototheranostics.

Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.

Metal-Coordinated NIR-II Nanoadjuvants with Nanobody Conjugation for Potentiating Immunotherapy by Tumor Metabolism Reprogramming.

Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high-lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody-engineered NIR-II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR-II photothermal-ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS-Nb) is prepared by metallic iron ion-mediated coordination self-assembly of D-A-D type NIR-II molecules and loading of glycolysis inhibitor, 2-deoxy-D-glucose (2DG), followed by modification with aPD-L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR-II fluorescence/photoacoustic imaging while initiating NIR-II photothermal-ferroptosis therapy. The remarkable NIR-II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti-tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR-II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti-tumor immunotherapy combined with ICB therapy.

A biomimetic cuproptosis amplifier for targeted NIR-II fluorescence/photoacoustic imaging-guided synergistic NIR-II photothermal immunotherapy.

The therapeutic efficacy of cuproptosis combined with phototheranostics is still hindered by easy copper efflux, nonspecific accumulation and limited light penetration depth. Here, a high-performance NIR-II semiconductor polymer was first synthesized through dual-donor engineering. Then a biomimetic cuproptosis amplifier (PCD@CM) was prepared by Cu(II)-mediated coordinative self-assembly of NIR-II ultrasmall polymer dots and the chemotherapeutic drug DOX, followed by camouflaging of tumor cell membranes. After homologous targeting delivery to tumor cells, overexpressed GSH in the tumor microenvironment (TME) triggers the disassembly of the amplifier and the release of therapeutic components through the reduction of Cu(II) to Cu(I), which enable NIR-II fluorescence/photoacoustic imaging-guided NIR-II photothermal therapy (PTT) and chemotherapy. The released Cu(I) induces the aggregation of lipoylated mitochondrial proteins accompanied by the loss of iron-sulfur proteins, leading to severe proteotoxic stress and eventually cuproptosis. NIR-II PTT and GSH depletion render tumor cells more sensitive to cuproptosis. The amplified cuproptosis sensitization provokes significant immune surveillance, triggering the immunogenic cell death (ICD) to promote cytotoxic T lymphocyte infiltration together with aPD-L1-mediated immune checkpoint blockade. This work proposes a new strategy to develop cuproptosis sensitization systems enhanced by NIR-II phototheranostics with homologous targeting and anti-tumor immune response capabilities.

Phenylboronic Acid-Modified Near-Infrared Region II Excitation Donor-Acceptor-Donor Molecule for 2-Deoxy-d-Glucose Improved Starvation/Chemo/Photothermal Combination Therapy.

Synergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermoresistance performance of tumor cells, and low drug bioavailability. Herein, multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near-infrared region II (NIR-II) light excitation donor-acceptor-donor (D-A-D) small molecules, doxorubicin (DOX), and 2-deoxy-d-glucose (2-DG) are developed for reinforced starvation/chemo/NIR-II PTT combination therapy. The synthesized phenylboronic acid (PBA)-modified water-soluble D-A-D molecule (BBT-TF-PBA) not only exhibits high binding ability to DOX and 2-DG through donor-acceptor coordination interactions PBA-diol bonds but also serves as a photoactive agent for NIR-II fluorescence imaging, NIR-II photoacoustic imaging, and NIR-II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor-acceptor coordination interactions and PBA-diol bond are decomposed, simultaneously releasing DOX and 2-DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2-DG also effectively inhibits the expression of heat shock protein and further enhances NIR-II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrate the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR-II PTT, and starvation therapy.

Self-delivery of metal-coordinated NIR-II nanoadjuvants for multimodal imaging-guided photothermal-chemodynamic amplified immunotherapy.

The effectiveness of phototheranostics induced immunotherapy is still hampered by limited light penetration depth, the complex immunosuppressive tumor microenvironment (TME) and the low efficiency of immunomodulator drug delivery. Herein, self-delivery and TME responsive NIR-II phototheranostic nanoadjuvants (NAs) were fabricated to suppress the growth and metastasis of melanoma through the integration of photothermal-chemodynamic therapy (PTT-CDT) and immune remodeling. The NAs were constructed by the self-assembly of ultrasmall NIR-II semiconducting polymer dots and the toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn2+) as coordination nodes. Under acidic TME, the NAs responsively disintegrated and released therapeutic components, which enable NIR-II fluorescence/photoacoustic/magnetic resonance imaging-guided tumor PTT-CDT. Moreover, the synergistic treatment of PTT-CDT could induce significant tumor immunogenic cell death and evoke highly efficacious cancer immunosurveillance. The released R848 stimulated the maturation of dendritic cells, which both amplified the antitumor immune response by modulating and remodeling the TME. The NAs present a promising integration strategy of polymer dot-metal ion coordination and immune adjuvants for precise diagnosis and amplified anti-tumor immunotherapy against deep-seated tumors. STATEMENT OF SIGNIFICANCE: The efficiency of phototheranostics induced immunotherapy is still limited by insufficient light penetration depth, low immune response and the complex immunosuppressive tumor microenvironment (TME). In order to improve the efficacy of immunotherapy, self-delivery NIR-II phototheranostic nanoadjuvants (PMR NAs) were successfully fabricated via the facile coordination self-assembly of ultra-small NIR-II semiconducting polymer dots and toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn2+) as coordination nodes. PMR NAs not only enable TME responsive cargo release and NIR-II fluorescence/photoacoustic/magnetic resonance imaging mediated precise localization of tumors, but also achieve synergistic photothermal-chemodynamic therapy, evoking an effective anti-tumor immune response by ICD effect. The responsively released R848 could further amplify the efficiency of immunotherapy by reversing and remodeling the immunosuppressive tumor microenvironment, thereby effectively inhibiting tumor growth and lung metastasis.

Graphene-CdS nanocomposites: facile one-step synthesis and enhanced photoelectrochemical cytosensing.

Graphene-CdS (GR-CdS) nanocomposites were prepared in a one-step synthesis in aqueous solution. The synthetic approach was simple and fast, and it may be extended for the synthesis of other GR-metal-sulfide nanocomposites. The as-prepared GR-CdS nanocomposite films inherited the excellent electron-transport properties of GR. In addition, the heteronanostructure of the GR-CdS nanocomposites facilitated the spatial separation of the charge carriers, thus resulting in enhanced photocurrent intensity, which makes it a promising candidate for photoelectrochemical applications. This strategy was used for the fabrication of an advanced photoelectrochemical cytosensor, based on these GR-CdS nanocomposites, by using a layer-by-layer assembly process. This photoelectrochemical cytosensor showed a good photoelectronic effect and cell-capture ability, and had a wide linear range and low detection limit for Hela cells. The as-synthesized GR-CdS nanocomposites exhibited obviously enhanced photovoltaic properties, which could be an efficient platform for many other high-performance photovoltaic devices.

Fabrication of glutathione photoelectrochemical biosensor using graphene-CdS nanocomposites.

A novel glutathione (GSH) photoelectrochemical biosensor was fabricated using the newly synthesized graphene-CdS (GR-CdS) nanocomposites. The GR-CdS nanocomposites were prepared by a fast, one-step, aqueous reaction. The as-prepared GR-CdS structure inherited the excellent electron transport of GR and facilitated the spatial separation of photo-generated charge carrier, therefore resulting in the enhanced photocurrent, and making it a promising candidate for developing photoelectrochemical biosensors. The proposed GSH sensor displays satisfactory analytical performance with an acceptable linear range from 0.01 to 1.5 mmol L(-1) with a detection limit of 0.003 mmol L(-1) at a signal-to-noise ratio of 3, and also shows an excellent specificity against anticancer drugs and can be successfully applied for GSH detection in real samples. The as-synthesized GR-CdS nanocomposites exhibited obviously enhanced photovoltaic properties, which could be extended to the detection of other enzymes and biomolecules, thus providing a promising platform for the development of photoelectrochemical biosensors.