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Over the last decades, a variety of metal complexes have been developed as chemotherapeutic agents. Despite the promising therapeutic prospects, the vast majority of these compounds suffer from low solubility, poor pharmacological properties, and most importantly poor tumor accumulation. To circumvent these limitations, herein, the incorporation of cytotoxic Ir(III) complexes and a variety of photosensitizers into polymeric gemini nanoparticles that selectively accumulate in the tumorous tissue and could be activated by near-infrared (NIR) light to exert an anticancer effect is reported. Upon exposure to light, the photosensitizer is able to generate singlet oxygen, triggering the rapid dissociation of the nanostructure and the activation of the Ir prodrug, thereby initiating a cascade of mitochondrial targeting and damage that ultimately leads to cell apoptosis. While selectively accumulating into tumorous tissue, the nanoparticles achieve almost complete eradication of the cisplatin-resistant cervical carcinoma tumor in vivo upon exposure to NIR irradiation., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (P mt ) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (P Bodipy ). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NP Bodipy ) which could further accumulate at the tumor and destroy cell membranes through electrostatic interactions, resulting in cell membrane destabilization. Meanwhile, the photosensitizer Bodipy produces ROS to induce damage to cell membranes, proteins, and DNAs to kill cancer cells concertedly, finally resulting in cell membrane lysis and cancer cell death. This work highlights the use of near-infrared light to spatially and temporarily control cationic polymers for photodynamic therapy, photo-immunotherapy, and NIR-II fluorescence for bio-imaging., (© 2024. The Author(s).)

The integration of nanomedicine and immunotherapy has presented a promising opportunity for the treatment of cancer and diverse diseases. However, achieving spatiotemporal controllable immunotherapy with excellent efficacy and safety performances remains a significant challenge. This study develops a biodegradable near-infrared II (NIR-II) photothermal response polymer nanoparticle (PTEQ) system. This platform exhibits intrinsic immunostimulatory properties while concurrently delivering siRNA for Programmed Death-Ligand 1 (siPD-L1), leveraging enhanced immune responses and immune checkpoint blockade for safe and effective cancer therapy. In the CT26 tumor-bearing mouse model, PTEQ, as an immune stimulant, significantly boosts the infiltration of CD4 + and CD8 + T cells within the tumor microenvironment (TME). The PTEQ/siPD-L1+laser group not only initiates NIR-II photothermal therapy but also promotes the activation and infiltration of T cells, M1 macrophage polarization, and maturation of dendritic cells in the TME, resulting in the complete elimination of tumors in 7/10 cases, achieving a 100% survival rate. In another in vivo vaccine experiment, all tumors on the right side are completely eliminated in the PTEQ/siPD-L1+laser group, reaching a 100% tumor eradication rate. These findings underscore the potential of this strategy to overcome the current immunotherapeutic limitations and achieve immune therapy normalization., (© 2024 Wiley‐VCH GmbH.)

Mild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers P M123 with photothermal units and P Fc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG 2000 into nanoparticle NP M123/Fc . NP M123/Fc under 1064 nm laser irradiation (NP M123/Fc +NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H 2 O 2 , displaying a strong synergistic photothermal and chemodynamic effect. NP M123/Fc +NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NP M123/Fc +NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NP M123/Fc +NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NP M123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NP M123/Fc +NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Photodynamic therapy (PDT), as a new type of light-mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non-resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen-dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed. Herein, a near-infrared light-activated photosensitive polymer is synthesized and branched the anti-metastatic ruthenium complex NAMI-A on the side, which is further assembled to form nanoparticles (NP2) for breast cancer therapy. NP2 can kill tumor cells by generating ROS under 808 nm radiation (NP2 + L), reduce the expression of matrix metalloproteinases (MMP2/9) in cancer cells, decrease the invasive and migration capacity of cancer cells, and eliminate cancer cells. Further animal experiments show that NP2 + L can inhibit tumor growth and reduce liver and lung metastases. In addition, NP2 + L can activate the immune system in mice to avoid tumor recurrence. In conclusion, a PDT capable of both preventing tumor metastasis and precisely hitting the primary tumor to achieve effective treatment of highly metastatic cancers is developed., (© 2024 Wiley‐VCH GmbH.)

Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Photodynamic therapy (PDT) and photothermal therapy (PTT) leverage reactive oxygen species (ROS) and control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria and nucleus, activating the cGAS-STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered by limitations such as suboptimal tumor targeting, aggregation-caused quenching (ACQ), and restricted excitation and emission wavelengths. Here, this work designs novel nanoparticles based on aggregation-induced emission (AIE) photosensitizer (BODTPE) for targeted tumor therapy and near-infrared II fluorescence imaging (NIR-II FLI) with enhanced PDT/PTT effects. BODTPE is employed as a monomer, dibenzocyclooctyne (DBCO)-PEG 2k -amine serving as an end-capping polymer, to synthesize a BODTPE-containing polymer (DBD). Further, through self-assembly, DBD and mPEG-DSPE 2k combined to form nanoparticles (NP-DBD). Notably, the DBCO on the surface of NP-DBD can react with azide groups on cancer cells pretreated with Ac 4 ManNAz through a copper-free click reaction. This innovative formulation led to targeted accumulation of NP-DBD within tumor sites, a phenomenon convincingly demonstrated in murine tumor models subjected to N-azidoacetylmannosamine-tetraacylated (Ac 4 ManNAz) pretreatment. Significantly, NP-DBD exhibits a multifaceted effect encompassing PDT/PTT/NIR-II FLI upon 808 nm laser irradiation, thereby better activating the cGAS-STING pathway, culminating in a compelling tumor inhibition effect augmented by robust immune modulation., (© 2023 Wiley-VCH GmbH.)

Photodynamic therapy (PDT) has achieved great success in cancer treatment. Despite its great promise, the efficacy of photodynamic immunotherapy can be limited by the hypoxia in solid tumors which is closely related to the abnormal tumor vasculature. These abnormal vasculatures are a hallmark of most solid tumors and facilitate immune evasion. Therefore, tumor vascular normalization is developed as a promising strategy to overcome tumor hypoxia, resulting in improved cancer therapy. Here, a NIR-II bio-degradable pseudo-conjugate polymer (PSP)-based photodynamic polymer is designed to deliver a vascular normalization agent, i.e., regorafenib (Reg) in nanoparticles (NP-PDT@Reg). NP-PDT@Reg under 808 nm laser irradiation (NP-PDT@Reg + L) can efficiently release Reg to improve the tumor hypoxia via vascular normalization, making more NP-PDT@Reg and oxygen enter the tumors. Moreover, NP-PDT@Reg + L can further result in generation of more reactive oxygen species (ROS) to eradicate tumor cells while inducing immunogenic cell death (ICD) to activate anti-tumor immune responses. In addition, Reg can reprogram TAM from a pro-tumor M2 phenotype to a tumor-killing M1 phenotype as well, thereby reversing the immunosuppressive tumor microenvironment. Taken together, the current study provides an innovative perspective on the development of novel nanomaterials to overcome the limitations in photodynamic immunotherapy., (© 2023 Wiley-VCH GmbH.)

Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial-temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo-conjugated-polymer is designed via Stille polymerization, resulting in PSP-Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR-II light. PSP-Pt can co-assemble with a commercially available lipid polymer, namely mPEG 2k -DSPE, into NP PSP-Pt . Under 1064 nm light irradiation, NP PSP-Pt can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo-immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR-II light for accelerating Pt(IV) reduction for cancer tumor therapy., (© 2023 Wiley-VCH GmbH.)

The development of Pt IV prodrugs that are reduced into the therapeutically active Pt II species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of Pt IV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of Pt IV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

As a DNA damaging agent, oxaliplatin (OXA) can induce immunogenic cell death (ICD) in tumors to activate the immune system. However, the DNA damage induced by OXA is limited and the ICD effect is not strong enough to enhance anti-tumor efficacy. Here, we propose a strategy to maximize the ICD effect of OXA through the mild hyperthermia generated by nanoparticles with a platinum (IV) prodrug of OXA (Pt(IV)-C16) and a near-infrared-II (NIR-II) photothermal agent IR1061 upon the irradiation of NIR-II light. The mild hyperthermia (43 °C) holds advantages in two aspects: 1) increase the Pt-DNA cross-linking, leading to enhanced DNA damage and apoptosis; 2) induce stronger ICD effects for cancer immunotherapy. We demonstrated that, compared with OXA and photothermal therapy of IR1061 alone, these nanoparticles under NIR-II light irradiation can significantly improve the anti-cancer efficacy against triple-negative breast cancer 4T1 tumor. This new strategy provides an effective way to improve the therapeutic outcome of OXA. STATEMENT OF SIGNIFICANCE: OXA could induce immunogenic cell death (ICD) via stimulating immune responses by increasing tumor cell stress and death, which triggers tumor-specific immune responses to achieve immunotherapy. However, due to the insufficient Pt-DNA crosslinks, the ICD effect triggered by OXA cannot induce robust immune response. Mild hyperthermia has great potential to maximize the therapeutic outcome of oxaliplatin by increasing the Pt-DNA cross-linking to augment the immunoresponse for enhanced cancer immunotherapy., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

cGAS-STING pathway, as an essential intracellular immune response pathway, has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate cGAS-STING pathway and induce immune response by DNA damage. Nevertheless, the ability of chemotherapeutic drugs to activate STING is so weak that new strategies are required to improve drug delivery efficiency for enhanced DNA damage, and then efficiently activate cGAS-STING pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which can be triggered to release cisplatin and CPT in tumor cells. CPT-Pt (IV) with high hydrophobicity is further self-assembled with a ROS sensitive polymer (P1) and mPEG 2k -DSPE into ROS responsive nanoparticles (NPs). NPs could accumulate in the tumor site to release cisplatin and CPT, resulting in DNA double damage and finally activating cGAS-STING pathway, inducing DC cells maturation and increasing tumor infiltration of CD8 + T cells on colorectal cancer mouse model. This study showed that common DNA targeted drugs can activate the cGAS-STING pathway in situ via nano delivery system, and enhance the effect of chemotherapy and immunotherapy, which provide a new strategy for clinical antitumor therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent progress in studying copper-dependent targets and pathways in the context of tumor treatment has provided new insights into therapeutic strategies of leveraging copper-dependent disease vulnerabilities and pharmacological manipulation of intratumor copper transportation to improve chemotherapy. Here, we developed reactive oxygen species (ROS)-sensitive nanoparticles loaded with copper chaperone inhibitor DC_AC50 and cisplatin(IV) prodrug. The released DC_AC50 can promote a remarkable accumulation of intracellular cisplatin and copper through inhibition of the Atox1-ATPase pathways, thereby enhancing the chemotherapeutic effect of cisplatin and inducing significant ROS generation. Excessive ROS then elicits intense endoplasmic reticulin (ER) stress which facilitates the immunogenic cell death (ICD) spurring a sustained immune response. Our study suggests that nanoparticle-mediated copper chaperone inhibition via DC_AC50 can restore the immunogenicity of tumor cells for enhanced chemotherapy and cancer immunotherapy., (© 2022 Wiley-VCH GmbH.)

Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self-sacrificially biodegradable pseudo-semiconducting polymer (PSP) for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co-assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)-responsive thioketal linkages (PE DOX ), which are denoted as NP@PE DOX /PSP. The NP@PE DOX /PSP can accumulate at tumor sites and generate ROS for photodynamic immunotherapy as well as near-infrared-II fluorescence (NIR-II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PE DOX , resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PE DOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PE DOX /PSP. This work highlights the application of self-sacrificially degradable PSP for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy., (© 2022 Wiley-VCH GmbH.)

Photothermal therapy based on conjugated polymers represents a promising antibacterial strategy but still possesses notable limitations. Herein, degradable pseudo conjugated polymers (PCPs) containing photothermal molecular backbones and reactive oxygen species (ROS)-sensitive thioketal bonds are designed. Triphenylphosphine (PPh 3 ) is introduced into PCPs to generate phosphonium-based PCPs (pPCPs), which further assembled with hyaluronic acid into pPCP nanoparticles (pPCP-NPs). pPCP-NPs with quaternary phosphonium cations selectively anchor on and destroy bacterial cell membranes through electrostatic action. Under 1064 nm laser irradiation, pPCP-NPs (pPCP-NPs/+L) produce near-infrared-II (NIR-II) photothermal antibacterial effect, thereby killing bacteria in a sustained manner. pPCP-NPs are readily degraded upon ROS abundant at infection sites, therefore exhibiting enough biosafety. pPCP-NPs/+L display an almost 100% bacterial inhibition rate in vitro and resultin a nearly complete recovery of bacteria-induced mouse wounds. A further metabolomics analysis denotes that pPCP-NPs/+L work in a concerted way to induce bacterial DNA damage, inhibit bacterial carbon/nitrogen utilization and amino acid/nucleotide synthesis. Taken together, degradable pPCP-NPs with both NIR-II photothermal effect and cationic phosphonium structural bacteriostasis provide a new avenue for antibiotics-alternative anti-infection therapy., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Recent progress in studying copper‐dependent targets and pathways in the context of tumor treatment has provided new insights into therapeutic strategies of leveraging copper‐dependent disease vulnerabilities and pharmacological manipulation of intratumor copper transportation to improve chemotherapy. Here, we developed reactive oxygen species (ROS)‐sensitive nanoparticles loaded with copper chaperone inhibitor DC_AC50 and cisplatin(IV) prodrug. The released DC_AC50 can promote a remarkable accumulation of intracellular cisplatin and copper through inhibition of the Atox1‐ATPase pathways, thereby enhancing the chemotherapeutic effect of cisplatin and inducing significant ROS generation. Excessive ROS then elicits intense endoplasmic reticulin (ER) stress which facilitates the immunogenic cell death (ICD) spurring a sustained immune response. Our study suggests that nanoparticle‐mediated copper chaperone inhibition via DC_AC50 can restore the immunogenicity of tumor cells for enhanced chemotherapy and cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Herein, composites of tin‐assisted antimony sulfide decorated on reduced graphene oxide (Sn@Sb2S3‐rGO) were prepared by using a simple hydrothermal method. As an anode material of sodium‐ion batteries, the Sn@Sb2S3‐rGO composites exhibited good electrochemical performance with an initial discharge (sodiation) specific capacity of 1002.0 mAh g−1, and they maintained a specific capacity of approximately 600 mAh g−1 at a current density of 200 mA g−1 after 60 cycles. The good performances could be explained by the composite with graphene and a bimetallic synergistic effect, both of which have an impact on the structure of Sb2S3 and subsequent electrochemical performance. This approach to the bimetallic synergistic effect for graphene composites could be a promising new idea to design other high‐performance energy storage materials. [ABSTRACT FROM AUTHOR]

Despite the high clinical success of cisplatin, this compound is associated with insufficient intracellular uptake and quick excretion from cancer cells, resulting in poor drug efficacy. To overcome these limitations, herein, a nanoparticle formulation for efficient drug delivery and high therapeutic effect towards challenging cancer tumors by multimodal chemotherapy and immunotherapy is reported. The nanoparticles are generated upon self-assembly of a polymerizable Pt(IV) prodrug with axial acrylates, a near-infrared II polymer that can generate heat, and a thermosensitive polymer with azo bonds that can generate radicals upon exposure to heat. The nanoparticles are found with a higher cellular uptake than the molecular drug cisplatin. Upon exposure to irradiation at 1064 nm, the azo bonds are broken, and therapeutically active radicals as well as the Pt(IV) complex simultaneously released. Due to the presence of reactive acrylate moieties, the metal complex is able to undergo in-situ polymerization inside the cancer cells, resulting in the formation of a cross-linked polymeric network and therefore the retention of the cisplatin and reduction of the cisplatin efflux in the cancer cells, triggering cell death by a combination of apoptosis and immunogenic cell death. Based on these promising effects, the therapeutic efficiency is evaluated in a clinically highly challenging ovarian cancer patient-derived xenograft mouse model as well as an ID8 subcutaneous tumor-bearing C57BL/6 mouse model. This study reports on the first example of a nanoparticle delivery system with Pt(IV) prodrugs that can polymerize within cancer cells, thereby resulting in a decrease in cisplatin efflux, efficient DNA damage, and effective immunogenic response. [Display omitted] ● A polymerizable Pt(IV) prodrug with axial acrylates moieties was synthesized. ● NPPt/Azo/PTT+L was developed to trigger intracellular Pt(IV) polymerization. ● NPPt/Azo/PTT+L decreased Pt efflux and promoted DNA damage in cancer cells. ● NPPt/Azo/PTT+L induced ICD and reprogramed tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Converting solar energy into sustainable hydrogen fuel by photoelectrochemical (PEC) water splitting is a promising technology to solve increasingly serious global energy supply and environmental issues. However, the PEC performance based on TiO2 nanomaterials is hindered by the limited sunlight-harvesting ability and its high recombination rate of photogenerated charge carriers. In this work, layered SnS2 absorbers and CoOx nanoparticles decorated two-dimensional (2D) TiO2 nanosheet array photoelectrode have been rationally designed and successfully synthesized, which remarkably enhanced the PEC performance for water splitting. As the result, photoconversion efficiency of TiO2/SnS2/CoOx and TiO2/SnS2 hybrid photoanodes increases by 3.6 and 2.0 times under simulated sunlight illumination, compared with the bare TiO2 nanosheet arrays photoanode. Furthermore, the TiO2/SnS2/CoOx photoanode also presented higher PEC stability owing to CoOx catalyst served as efficient water oxidation catalyst as well as an effective protectant for preventing absorber photocorrosion. [ABSTRACT FROM AUTHOR]

Solar radiation shielding properties of transparent LaB 6 filters were investigated experimentally and by a first-principles method. It was found that the calculated solar radiation shielding performances for transparent LaB 6 filters are in excellent agreement with experimental findings. The results indicate that LaB 6 is a promising near infrared (NIR) shielding material for solar radiative filters with high visible light transmittance and perfect optical performance that can be applied not only to compacted filters but also in the nanoparticle dispersed coatings. [ABSTRACT FROM AUTHOR]