Acidity-responsive polyphenol-coordinated nanovaccines for improving tumor immunotherapy via bidirectional reshaping of the immunosuppressive microenvironment and controllable release of antigens.

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. FeIII was coordinated with TA-OVA to produce a FeIII-TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between FeIII and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.

Surface-Initiated Polymerization with an Initiator Gradient: A Monte Carlo Simulation.

Due to the difficulty of accurately characterizing properties such as the molecular weight (Mn) and grafting density (σ) of gradient brushes (GBs), these properties are traditionally assumed to be uniform in space to simplify analysis. Applying a stochastic reaction model (SRM) developed for heterogeneous polymerizations, we explored surface-initiated polymerizations (SIPs) with initiator gradients in lattice Monte Carlo simulations to examine this assumption. An initial exploration of SIPs with 'homogeneously' distributed initiators revealed that increasing σ slows down the polymerization process, resulting in polymers with lower molecular weight and larger dispersity (D) for a given reaction time. In SIPs with an initiator gradient, we observed that the properties of the polymers are position-dependent, with lower Mn and larger D in regions of higher σ, indicating the non-uniform properties of polymers in GBs. The results reveal a significant deviation in the scaling behavior of brush height with σ compared to experimental data and theoretical predictions, and this deviation is attributed to the non-uniform Mn and D.

Size-Switchable Ru Nanoaggregates for Enhancing Phototherapy: Hyaluronidase-Triggered Disassembly to Alleviate Deep Tumor Hypoxia.

Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions in situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 in situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15 nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.

Dual-Labeled Single Fluorescent Probes for the Simultaneous Two-Color Visualization of Dual Organelles and for Monitoring Cell Autophagy.

Dual-labeled single fluorescent probes are powerful tools for studying autophagy on the molecular scale, yet their development has been hampered by design complexity and a lack of valid strategies. Herein, for the first time, we introduce a combinatorial regulation strategy to fabricate dual-labeled probes for studying autophagy by integrating the specific organelle-targeting group and the functional fluorescence switch into a pentacyclic pyrylium scaffold (latent dual-target scaffold). For proof of concept, we prepared a range of dual-labeled probes (TMOs) that display different emission colors in duple organelles. In these probes, TMO1 and TMO2 enabled the simultaneous two-color visualization of the lysosomes and mitochondria. The other probes (TMO3 and TMO4) discriminatively targeted lysosomes/nucleolus and lysosomes/lipid droplets (LDs) with dual-color emission characteristics, respectively. Intriguingly, by simply connecting the endoplasmic reticulum (ER) targeting group to the pentacyclic pyrylium scaffold, we created the first dual-labeled probe TMO5 for simultaneously labeling lysosomes/ER in distinctive fluorescent colors. Subsequently, using the dual-labeled probe TMO2, drug-induced mitophagy was successfully recorded by evaluating the alterations of multiple mitophagy-related parameters, and the mitophagy defects in a cellular model of Parkinson's disease (PD) were also revealed by simultaneous dual-color/dual-organelle imaging. Further, the probe TMO4 can track the movement of lysosomes and LDs in real time and monitor the dynamic process of lipophagy. Therefore, this work not only presents attractive dual-labeled probes to promote the study of organelle interactions during autophagy but also provides a promising combinatorial regulation strategy that may be generalized for designing other dual-labeled probes with multiple organelle combinations.

Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy.

Chemodynamic immunotherapy that utilizes catalysts to produce reactive oxygen species (ROS) for killing tumor cells and arousing antitumor immunity has received considerable attention. However, it is still restricted by low ROS production efficiency and insufficient immune activation, due to intricate redox homeostasis in the tumor microenvironment (TME). Herein, a metalloprotein-like hybrid nanozyme (FeS@GOx) is designed by in situ growth of nanozyme (ferrous sulfide, FeS) in a natural enzyme (glucose oxidase, GOx) to amplify ROS cascade for boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows the conversion of endogenous glucose to gluconic acid and hydrogen peroxide, which provides favorable increasing hydrogen peroxide for subsequent Fenton reaction of FeS nanozymes, thus reinforcing ROS production. Notably, hydrogen sulfide (H2 S) release is activated by the gluconic acid generation-related pH decrease, which can suppress the activity of endogenous thioredoxin reductase and catalase to further inhibit ROS elimination. Thus, FeS@GOx can sustainably amplify ROS accumulation and perturb intracellular redox homeostasis to improve chemodynamic therapy and trigger robust immunogenic cell death for effective immunotherapy combined with immune checkpoint blockade. This work proposes a feasible H2 S amplified ROS cascade strategy employing a bioinspired hybrid nanozyme, providing a novel pathway to multi-enzyme-mediated TME modulation for precise and efficient chemodynamic immunotherapy.

Copper-Nitrogen-Coordinated Carbon Dots: Transformable Phototheranostics from Precise PTT/PDT to Post-Treatment Imaging-Guided PDT for Residual Tumor Cells.

Phototheranostics has attracted considerable attention in the fields of cancer diagnosis and treatment. However, the complete eradication of solid tumors using traditional phototheranostics is difficult because of the limited depth and range of laser irradiation. New phototheranostics enabling precise phototherapy and post-treatment imaging-guided programmed therapy for residual tumors is urgently required. Accordingly, this study developed a novel transformable phototheranostics by assembling hyaluronic acid (HA) with copper-nitrogen-coordinated carbon dots (CDs). In this transformable nanoplatform, named copper-nitrogen-CDs@HA, the HA component enables the specific targeting of cluster determinant (CD) 44-overexpressing tumor cells. In the tumor cells, redox glutathione converts Cu(II) (cupric ions) into Cu(I) (cuprous ions), which confers the novel transformable functionality to phototheranostics. Both in vitro and in vivo results reveal that the near-infrared-light-photoactivated CuII-N-CDs@HA could target CD44-overexpressing tumor cells for precise synergistic photothermal therapy and photodynamic therapy. This study is the first to observe that CuII-N-CDs@HA could escape from lysosomes and be transformed in situ into CuI-N-CDs@HA in tumor cells, with the d9 electronic configuration of Cu(II) changing to the d10 electronic configuration of Cu(I), which turns on their fluorescence and turns off their photothermal properties. This transformable phototheranostics could be used for post-treatment imaging-guided photodynamic therapy on residual tumor cells. Thus, the rationally designed copper-nitrogen-coordinated CDs offer a simple in situ transformation strategy for using multiple-stimulus-responsive precise phototheranostics in post-treatment monitoring of residual tumor cells and imaging-guided programmed therapy.

In Situ Polymerization of Aniline Derivative in Vivo for NIR-II Phototheranostics of Tumor.

Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.

H2O2-activated in situ polymerization of aniline derivative in hydrogel for real-time monitoring and inhibition of wound bacterial infection.

Wound is highly susceptible to bacterial infection, which can cause chronic wound and serial complications. However, timely treatment is hampered by the lack of real-time monitoring of wound status and effective therapeutic systems. Herein, in situ biosynthesis of functional conjugated polymer in artificial hydrogel was developed via the utilization of biological microenvironment to realize monitoring in real time of wound infection and inhibition of bacteria for the first time. Specially, an easily polymerizable aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) in calcium alginate hydrogel, which was initiated via the catalysis of hydrogen peroxide (H2O2) overexpressed in infected wound to produce hydroxyl radical (•OH) by preloaded horseradish peroxidase (HRP). Benefitting from outstanding near infrared (NIR) absorption of PSPA, such polymerization can be ingeniously used for real-time monitoring of H2O2 via naked-eye and photoacoustic signal, as well as NIR light-mediated photothermal inhibition of bacteria. Furthermore, combining the persistent chemodynamic activity of •OH, the in vivo experimental data proved that the wound healing rate was 99.03% on the 11th day after treatment. Therefore, the present work opens the way to manipulate in situ biosynthesis of functional conjugated polymer in artificial hydrogels for overcoming the issues on wound theranostics.

A Simple Stochastic Reaction Model for Heterogeneous Polymerizations.

The stochastic reaction model (SRM) treats polymerization as a pure probability-based issue, which is widely applied to simulate various polymerization processes. However, in many studies, active centers were assumed to react with the same probability, which cannot reflect the heterogeneous reaction microenvironment in heterogeneous polymerizations. Recently, we have proposed a simple SRM, in which the reaction probability of an active center is directly determined by the local reaction microenvironment. In this paper, we compared this simple SRM with other SRMs by examining living polymerizations with randomly dispersed and spatially localized initiators. The results confirmed that the reaction microenvironment plays an important role in heterogeneous polymerizations. This simple SRM provides a good choice to simulate various polymerizations.

Metallopolysaccharide-Based Smart Nanotheranostic for Imaging-Guided Precise Phototherapy and Sequential Enzyme-Activated Ferroptosis.

Phototheranostic offers a regional-focused tumor treatment upon photoirradiation. However, it is difficult to completely eradicate solid tumors using a conventional phototheranostic owing to the residual tumor cells outside the laser irradiation range. Herein, we fabricated a metallopolysaccharide-based smart nanotheranostic (Fe-dHA) via a nanoassembly-driven method, in which Fe3+ ions were coordinated to dopamine-modified biopolysaccharide hyaluronic acid (dHA). Taking advantage of the structural backbone and intrinsic dual-information-related functions of HA as well as the bi-functional Fe(III)-coordination centers, Fe-dHA can efficiently target tumor cells for phototheranostic. Additionally, it can be activated by endogenous overexpressed hyaluronidase to achieve sequential ferroptosis in tumor cells. The precise imaging and effective tumor inhibition using this metallopolysaccharide-based nanotheranostic were significantly demonstrated in vivo and in vitro. Thus, this rationally designed Fe-dHA provided a simple metallopolysaccharide strategy to develop an "all-in-one" smart nanotheranostic to synergize different therapeutic modalities for improving cancer therapy.

A General Approach to Design Dual Ratiometric Fluorescent and Photoacoustic Probes for Quantitatively Visualizing Tumor Hypoxia Levels In†Vivo.

Herein, we describe an energy balance strategy between fluorescence and photoacoustic effects by sulfur substitution to transform existing hemicyanine dyes (Cy) into optimized NIRF/PA dual ratiometric scaffolds. Based on this optimized scaffold, we reported the first dual-ratio response of nitroreductase probe AS-Cy-NO2 , which allows quantitative visualization of tumor hypoxia in vivo. AS-Cy-NO2 , composed of a new NIRF/PA scaffold thioxanthene-hemicyanine (AS-Cy-1) and a 4-nitrobenzene moiety, showed a 10-fold ratiometric NIRF enhancement (I773 /I733 ) and 2.4-fold ratiometric PA enhancement (PA730 /PA670 ) upon activation by a biomarker (nitroreductase, NTR) associated with tumor hypoxia. Moreover, the dual ratiometric NIRF/PA imaging accurately quantified the hypoxia extent with high sensitivity and high imaging depth in xenograft breast cancer models. More importantly, the 3D maximal intensity projection (MIP) PA images of the probe can precisely differentiate the highly heterogeneous oxygen distribution in solid tumor. Thus, this study provides a promising NIRF/PA scaffold that may be generalized for the dual ratiometric imaging of other disease-relevant biomarkers.

Stimuli-Responsive Nanomaterials for Smart Tumor-Specific Phototherapeutics.

Phototherapy, a type of photoresponsive regulation of biological activities, together with additional stimuli-responsive features, offers significant potential for enhancing the precision and efficacy of cancer treatments. To achieve tumor-specific therapeutics, numerous studies have focused on the development of smart phototherapeutic nanomaterials (PNMs) that can respond to endogenous pathological characteristics (e. g., mild acidity, the overproduction of glutathione, the overproduction of hydrogen peroxide, the overexpression of specific surface receptors, etc.) present in the tumor and/or exogenous stimuli. Such responsiveness can effectively improve the physicochemical properties, cellular uptake, tumor-targeting performance, and pharmacokinetic profile of PNMs. Herein, we will systematically discuss recent advances in this field. Moreover, potential challenges and future directions in the development of stimuli-responsive PNMs are also presented to support the development of this emerging cutting-edge research area.

Full-spectrum responsive ZrO2-based phototheranostic agent for NIR-II photoacoustic imaging-guided cancer phototherapy.

Second near-infrared (NIR-II) window responsive phototheranostic agents have a precise spatiotemporal potential for the diagnosis and treatment of cancer. In this study, a full-spectrum responsive ZrO2-based phototheranostic agent was found to achieve NIR-II photoacoustic (PA) imaging-guided tumour-targeting phototherapy. Initially, the ZrO2-based phototheranostic agent was fabricated through NaBH4 reduction to form boron-doped oxygen-deficient zirconia (ZrO2-x-B), an amino-functionalised SiO2 shell and a further covalent connection with hyaluronic acid (HA), namely, ZrO2-x-B@SiO2-HA. In the ZrO2-x-B@SiO2-HA system, the oxygen vacancy and boron doping resulted in full-spectrum absorption, enabling a high NIR-II photothermal conversion, high-resolution PA imaging ability and a remarkable production of reactive oxygen species (ROS). The surface modification of HA provided ZrO2-x-B@SiO2-HA with water dispersibility and a targeting capability for CD44 overexpressed cancer cells. Furthermore, in vitro and in vivo experiments showed that NIR-II activated ZrO2-x-B@SiO2-HA had a targeted photothermal/photodynamic effect for cancer elimination under the real-time guidance of NIR-II PAs. Hence, ZrO2-x-B@SiO2-HA displays a precise NIR-II radiation-activated phototheranostic potential for PA imaging-guided cancer-targeting photothermal/photodynamic therapy.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a "phototherapy-enzymatic" RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2 -hybridized OVA nanoanalogues (RuO2 @OVA NAs). The RuO2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

Natural Polyphenol-Vanadium Oxide Nanozymes for Synergistic Chemodynamic/Photothermal Therapy.

The selection of suitable nanozymes with easy synthesis, tumor specificity, multifunction, and high therapeutics is meaningful for tumor therapy. Herein, a facile one-step assembly approach was employed to successfully prepare a novel kind of natural polyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VOx NSs). In this system, VOx is assembled with TA through metal-phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V5+ to V4+ . The presence of mixed valence vanadium oxide in TA@VOx NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H2 O2 ) to . OH, and the corresponding catalytic mechanism of H2 O2 by TA@VOx NSs is proposed. Benefitting from such peroxidase-like activity of TA@VOx NSs, the overproduced H2 O2 of the tumor microenvironment allows the realization of tumor-specific chemodynamic therapy (CDT). As a valid supplement to CDT, the NIR absorption enables TA@VOx NSs to have NIR light-mediated conversion ability for photothermal therapy (PTT) of cancers. Furthermore, in vitro and in vivo experiments confirmed that TA@VOx NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT. These results offer a promising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.

A chloroplast-inspired nanoplatform for targeting cancer and synergistic photodynamic/photothermal therapy.

Specific targeting capabilities and effective phototherapeutic functions are the key demands for precise cancer phototherapeutic agents. Herein, a bioinspired nanoplatform composed of Cu(ii)-chlorophyll-hyaluronic acid nanoparticles (Cu(ii)Chl-HA NPs) was developed for targeting cancer and synergistic photodynamic/photothermal therapy. Inspired by the photonic biosystem of the chloroplast, Cu(ii) chlorophyll was used as a photosensitive substituent to covalently connect with a hydrophilic HA tail rather than a natural phytol tail, and this conjugate further assembled into a nanoparticle-like morphology under non-covalent interaction. Time-dependent density functional theory calculations reveal that the Cu(ii) chlorophyll has a much smaller energy gap between an excited singlet and excited triplet, and theoretically leads to rapid electron intersystem crossing that would benefit the PDT effect. In addition, a series of experiments have proven that, under 650 nm laser irradiation, the nanoplatform of Cu(ii)Chl-HA can produce a high amount of singlet oxygen and exhibit an outstanding photothermal conversion capability. More interestingly, owing to the specific interactions between the HA component and the CD44 receptor on the cell membrane, the HA tails impart Cu(ii)Chl-HA NPs an excellent receptor-mediated targeting performance toward CD44-overexpressing cancer cells. Based on these features, the nanoplatform of Cu(ii)Chl-HA NPs presents active targeting and outstanding dual modality synergistic PDT/PTT performance of cancer both in vitro and in vivo. Thus, this work opens up a new strategy to fabricate a bioinspired multifunctional cancer phototherapy nanoplatform.

An injectable thermosensitive photothermal-network hydrogel for near-infrared-triggered drug delivery and synergistic photothermal-chemotherapy.

Near-infrared (NIR)-responsive hydrogels have exhibited remarkable advantages in biomedical applications especially for in situ therapeutic delivery, because of their deep-tissue penetration capacity, minimal invasiveness, and high spatiotemporal selectivity. Nevertheless, conventional NIR-responsive nanocomposite hydrogels suffer from the disadvantages of limited photothermal effect and potential leakage of the physically mixed photothermal nanoagents. To overcome these limitations, we herein designed an injectable thermosensitive photothermal-network hydrogel (PNT-gel) through the host-guest self-assembly of a photothermal conjugated polymers and ɑ-cyclodextrin. The conjugated-polymer backbones can directly convert incident light into heat, endowing the PNT-gel with high photothermal conversion efficiency (η = 52.6%) and enhanced photothermal stability. Meanwhile, the mild host-guest assembly enable the shear-thinning injectability, photothermally-driven and reversible gel-sol conversion of the hydrogel. Consequently, the remotely controlled on-demand release of doxorubicin (DOX) was achieved via photothermal-induced gel-sol transition. Because the backbone of the hydrogel absorbs NIR light and mediates the photothermal conversion itself, the PNT-gel demonstrated the advantage of a prolonged retention time and thus permitting repeatable NIR treatment after a one-time intratumoral injection of this hydrogel. Under repeated NIR laser irradiation (0.15 W cm-2), the synergistic photothermal-chemotherapy mediated by the PNT-gel almost completely eradicated 4T1 breast cancer. This work not only presents a multifunctional therapeutic platform integrated with inherent photothermal characteristic and reversible stimuli responsiveness for on-demand delivery and combinatorial photothermal-chemotherapy, but also provides a new strategy for the development of the next-generation of light-modulated intelligent hydrogels. STATEMENT OF SIGNIFICANCE: The conventional NIR-responsive nanocomposite hydrogels suffer from the disadvantages of limited photothermal effect and possible leakage of the physically mixed photothermal nano-components. To overcome these limitations, we hereby fabricated a NIR-responsive themosensitive photothermal-network hydrogel through the supramolecular assembly of conjugated polymer. The conjugated polymeric backbones of the hydrogel directly convert NIR light to heat, endowing the hydrogel with good photothermal effect and long-term photothermal stability. Meanwhile, the dynamic crosslinkages via supramolecular assembly enabled the shear-thinning injectability and reversible gel-sol transition of the hydrogel, facilitating the photothermal-induced drug release. Our strategy demonstrated the efficacy of using conjugated polymer as the backbone of hydrogel for the construction of a new injectable NIR-responsive hydrogel system with enhanced photothermal capabilities and improved therapy outcomes.

NIR-II light-modulated thermosensitive hydrogel for light-triggered cisplatin release and repeatable chemo-photothermal therapy.

Cisplatin is one of the most effective chemotherapeutic agents, although its clinical use is limited by severe nephrotoxicity. Multifunctional platform for spatiotemporally controlled delivery of cisplatin and multimodal synergistic therapy is highly desirable in antitumor research. Herein, for the first time, an injectable, NIR-II light-modulated and thermosensitive hydrogel is synthesized through supramolecular self-assembly of a conjugated polymer and α-cyclodextrin. This hydrogel intrinsically features NIR responsive characteristics and thermo-responsive properties. The conjugated polymer (poly(N-phenylglycine)) not only tethers the poly(ethylene glycol) chains to enable the hydrogel formation, but also serves as the NIR-absorbing mediators. Accordingly, one particular benefit of this hydrogel is that its building blocks absorb NIR-II light and mediate the photothermal conversion itself, offering the important advantage of a prolonged retention time and thus permitting repeatable treatment upon a single-injection of this hydrogel. Under NIR-II laser irradiation, the localized photothermal effect not only ablates the highly metastatic triple-negative breast cancer (TNBC), but also triggers the on-demand cisplatin release through the thermo-responsive gel-sol transition, thus resulting in enhanced antitumor activity and reduced off-target toxicity. This work not only provides a novel multifunctional platform for NIR-triggered cisplatin release and chemo-photothermal combination therapy, but also presents a promising strategy for the rational design of NIR light-responsive hydrogels for the intervention of highly aggressive cancers.

Hypericin-Loaded Carbon Nanohorn Hybrid for Combined Photodynamic and Photothermal Therapy in Vivo.

Photodynamic therapy (PDT) of hypericin (Hyp) is hampered by poor water solubility and photostability. Incorporation of photosensitizers into nanocarriers has been designed to solve these issues. Herein, SWNH-Hyps nanohybrids were first fabricated by loading hypericin on the surface of single-walled carbon nanohorns (SWNHs) through ??? interaction and exhibited high solubility and stability in aqueous water. SWNH-Hyps could be utilized for a single platform for cancer therapy because it could simultaneously generate enough reactive oxygen species and hyperthermia using light irradiation. Moreover, the SWNHs not only improved water solubility, photostability, and therapy effects of Hyp but also protected it from light degradation. SWNH-Hyps could effectively ablate 4T1 cells by photodynamic/photothermal synergistic therapy upon 590 and 808 nm light irradiations compared with PDT. Furthermore, remarkable tumor cell death as well as tumor growth inhibition was proved via photothermal therapy and PDT of SWNH-Hyps under 590 and 808 nm light irradiations, which demonstrated that synergistic anticancer ability of SWNH-Hyps was better than that of free Hyp in vivo. Such a simple and facile adsorption method improved water solubility of Hyp and then enhanced its therapy effect, which displays that SWNHs can be hopefully used in medicines in the future.

The Persistence Length of Semiflexible Polymers in Lattice Monte Carlo Simulations.

While applying computer simulations to study semiflexible polymers, it is a primary task to determine the persistence length that characterizes the chain stiffness. One frequently asked question concerns the relationship between persistence length and the bending constant of applied bending potential. In this paper, theoretical persistence lengths of polymers with two different bending potentials were analyzed and examined by using lattice Monte Carlo simulations. We found that the persistence length was consistent with theoretical predictions only in bond fluctuation model with cosine squared angle potential. The reason for this is that the theoretical persistence length is calculated according to a continuous bond angle, which is discrete in lattice simulations. In lattice simulations, the theoretical persistence length is larger than that in continuous simulations.