PtSnBi Nanoplates Enable Photoacoustic Imaging-Guided Highly Efficient Photothermal Tumor Ablation.

The development of photothermal agents (PTAs) with robust photostability and high photothermal conversion efficiency is of great importance for cancer photothermal therapy. Herein, a novel PTA was created using two-dimensional intermetallic PtSnBi nanoplates (NPs), which demonstrated excellent photostability and biocompatibility with a high photothermal conversion efficiency of ∼61 % after PEGylation. More importantly, PtSnBi NPs could be employed as photoacoustic imaging contrast agents for tumor visualization due to their strong absorbance in the NIR range. In addition, both in vitro and in vivo experiments confirmed that PtSnBi NPs had a good photothermal efficacy under NIR laser irradiation. Therefore, the remarkable therapeutic characteristics of PtSnBi NPs make them a most promising candidate for cancer theranostics.

Near-infrared absorbing semiconducting polymer nanomedicines for cancer therapy.

As a new type of organic optical nanomaterials, semiconducting polymer nanoparticles (SPNs) have the advantages of good optical characteristics and photostability, low toxicity concerns, and relatively simple preparation processes. Particularly, near-infrared (NIR) absorbing SPNs have shown a great promise in biomedicine. In addition to acting as nanoprobes for molecular imaging, these SPNs can produce local heat and reactive oxygen species with the stimulation of NIR light, allowing photothermal therapy (PTT) and photodynamic therapy (PDT), respectively. Herein, we summarize the recent development of SPN-based nanomedicines for cancer therapy. The rational designs of SPNs for enhanced PTT, PDT, or combinational PTT/PDT to achieve effective ablation of tumor tissues are highlighted. Via loading/conjugating SPNs with other therapeutic elements (such as chemotherapeutic drugs and immunotherapeutic agents), phototherapy-combined chemotherapy or immunotherapy can be realized, which is then discussed. In especial, the constructions of SPN-based nanomedicines for NIR photoactivatable chemotherapy and immunotherapy are introduced with representative examples. Finally, we discuss the current challenges and key concerns of SPNs for their biomedical applications and give an outlook for their future clinical translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Activating Nanomedicines with Electromagnetic Energy for Deep-Tissue Induction of Immunogenic Cell Death in Cancer Immunotherapy.

Immunotherapy is an attractive approach for cancer therapy, while its antitumor efficacy is still limited, especially for non-immunogenic tumors. Nanomedicines can be utilized to convert the non-immunogenic "cold" tumors to immunogenic "hot" tumors via inducing immunogenic cell death (ICD), thereby promoting the antitumor immune response. Some nanomedicines that can produce local heat and reactive oxygen species upon the stimulation of electromagnetic energy are the main candidates for inducing the ICD effect. However, their applications are often restricted due to the poor tissue penetration depths of electromagnetic energy, such as light. By contrast, ultrasound, X-ray, alternating magnetic field, and microwave show excellent tissue penetration depths and thereby can be used for sonodynamic therapy, radiotherapy, magnetic hyperthermia therapy, and microwave ablation therapy, all of which can effectively induce ICD. Herein, the combination of deep-tissue electromagnetic energy with nanomedicines for inducing ICD and cancer immunotherapy are summarized. In particular, the designs of nanomedicines to amplify ICD effect in the presence of deep-tissue electromagnetic energy and sensitize tumors to various immunotherapies will be discussed. At the end of this review, a brief conclusion and discussion of current challenges and further perspectives in this subfield are provided.

Recent advances in dual- and multi-responsive nanomedicines for precision cancer therapy.

Nanomedicines have been regarded as a potential approach in the field of cancer treatment due to their unique advantages. Although improved therapeutic efficacy can be achieved, the applications of most traditional nanomedicines are still limited by severe side effects resulting from unintended retention of therapeutic agents in non-diseased tissues. To increase the controllability of therapeutic agent accumulation in targeting sites (such as tumors), stimuli-responsive nanomedicines that realize drug release in response to exogenous or endogenous stimuli have been developed. In these stimuli-responsive nanomedicines, most of them are activated by mono type of stimulus, and therefore show unsatisfactory selectivity and specificity. In contrast, dual- and multi-responsive nanomedicines that integrate different responsive components into a signal nanoplatform can allow drug release in a more safe and effective manner, leading to both improved therapeutic efficacy and reduced systemic toxicity. Herein, we summarize recent advances in precision cancer therapy by using dual- and multi-responsive nanomedicines. The design strategies and working mechanisms of these dual- and multi-responsive nanomedicines and their applications in chemotherapy, phototherapy, and immunotherapy of cancer are introduced in detail. The existing challenges and future prospects are finally discussed in anticipation of accelerating the clinical translation of these nanomedicines.

Tumor extracellular matrix modulating strategies for enhanced antitumor therapy of nanomedicines.

Nanomedicines have shown a promising strategy for cancer therapy because of their higher safety and efficiency relative to small-molecule drugs, while the dense extracellular matrix (ECM) in tumors often acts as a physical barrier to hamper the accumulation and diffusion of nanoparticles, thus compromising the anticancer efficacy. To address this issue, two major strategies including degrading ECM components and inhibiting ECM formation have been adopted to enhance the therapeutic efficacies of nanomedicines. In this review, we summarize the recent progresses of tumor ECM modulating strategies for enhanced antitumor therapy of nanomedicines. Through degrading ECM components or inhibiting ECM formation, the accumulation and diffusion of nanoparticles in tumors can be facilitated, leading to enhanced efficacies of chemotherapy and phototherapy. Moreover, the ECM degradation can improve the infiltration of immune cells into tumor tissues, thus achieving strong immune response to reject tumors. The adoptions of these two ECM modulating strategies to improve the efficacies of chemotherapy, phototherapy, and immunotherapy are discussed in detail. A conclusion, current challenges and outlook are then given.

Bioenzyme-based nanomedicines for enhanced cancer therapy.

Bioenzymes that catalyze reactions within living systems show a great promise for cancer therapy, particularly when they are integrated with nanoparticles to improve their accumulation into tumor sites. Nanomedicines can deliver toxic bioenzymes into cancer cells to directly cause their death for cancer treatment. By modulating the tumor microenvironment, such as pH, glucose concentration, hypoxia, redox levels and heat shock protein expression, bioenzyme-based nanomedicines play crucial roles in improving the therapeutic efficacy of treatments. Moreover, bioenzyme-mediated degradation of the major components in tumor extracellular matrix greatly increases the penetration and retention of nanoparticles in deep tumors and infiltration of immune cells into tumor tissues, thus enhancing the efficacies of chemotherapy, phototherapy and immunotherapy. In this review, we summarize the recent progresses of bioenzyme-based nanomedicines for enhanced cancer therapy. The design and working mechanisms of the bioenzyme-based nanomedicines to achieve enhanced chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy and immunotherapy are introduced in detail. At the end of this review, a conclusion and current challenges and perspectives in this field are given.

AgNPs/nGOx/Apra nanocomposites for synergistic antimicrobial therapy and scarless skin recovery.

The misuse of antimicrobials has caused a remarkable increase of antibiotic-resistant bacteria. Developing novel antimicrobial agents with high activity and low rates of resistance development is in great demand yet challenging. In this context, we developed a novel cascaded AgNPs/nGOx/Apra nanocomposite for combinational antimicrobial therapy. Glucose oxidase nanocapsules (nGOx) in the nanocomposites can convert tissue glucose into H2O2, which in turn accelerates the erosion of AgNPs into Ag+, giving rise to a synergistic antibiotic/starving-like/metal ion therapeutic effect. An in vitro antimicrobial study of the nanocomposites demonstrated rapid bacterial killing, significant bacterial growth inhibition and broad antimicrobial spectra at a low antibiotic dose. More importantly, topical and microneedle-assisted deliveries of the nanocomposites resulted in rapid scarless skin recovery in both rabbit and mouse models. This nanocomposite platform opens up a new avenue for research and clinical applications to battle against microbial infections and reduce antibiotic-resistant rates.

Extracellular matrix-degrading STING nanoagonists for mild NIR-II photothermal-augmented chemodynamic-immunotherapy.

Regulation of stimulator of interferon genes (STING) pathway using agonists can boost antitumor immunity for cancer treatment, while the rapid plasma clearance, limited membrane permeability, and inefficient cytosolic transport of STING agonists greatly compromise their therapeutic efficacy. In this study, we describe an extracellular matrix (ECM)-degrading nanoagonist (dNAc) with second near-infrared (NIR-II) light controlled activation of intracellular STING pathway for mild photothermal-augmented chemodynamic-immunotherapy of breast cancer. The dNAc consists of a thermal-responsive liposome inside loading with ferrous sulfide (FeS2) nanoparticles as both NIR-II photothermal converters and Fenton catalysts, 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as the STING agonist, and an ECM-degrading enzyme (bromelain) on the liposome surface. Mild heat generated by dNAc upon NIR-II photoirradiation improves Fenton reaction efficacy to kill tumor cells and cause immunogenic cell death (ICD). Meanwhile, the generated heat triggers a controlled release of cGAMP from thermal-responsive liposomes to active STING pathway. The mild photothermal activation of STING pathway combined with ICD promotes anti-tumor immune responses, which leads to improved infiltration of effector T cells into tumor tissues after bromelain-mediated ECM degradation. As a result, after treatment with dNAc upon NIR-II photoactivation, both primary and distant tumors in a murine mouse model are inhibited and the liver and lung metastasis are effectively suppressed. This work presents a photoactivatable system for STING pathway and combinational immunotherapy with improved therapeutic outcome.

Near-Infrared Photoactivatable Immunomodulatory Nanoparticles for Combinational Immunotherapy of Cancer.

As a promising treatment option for cancer, immunotherapy can eliminate local and distant metastatic tumors and even prevent recurrence through boosting the body's immune system. However, immunotherapy often encounters the issues of limited therapeutic efficacy and severe immune-related adverse events in clinical practices, which should be mainly due to the non-specific accumulations of immunotherapeutic agents. Activatable immunomodulatory agents that are responsive to endogenous stimuli in tumor microenvironment can afford controlled immunotherapeutic actions, while they still face certain extent of off-target activation. Since light has the advantages of noninvasiveness, simple controllability and high spatio-temporal selectivity, therapeutic agents that can be activated by light, particularly near-infrared (NIR) light with minimal phototoxicity and strong tissue penetrating ability have been programmed for cancer treatment. In this mini review, we summarize the recent progress of NIR photoactivatable immunomodulatory nanoparticles for combinational cancer immunotherapy. The rational designs, constructions and working mechanisms of NIR photoactivatable agents are first briefly introduced. The uses of immunomodulatory nanoparticles with controlled immunotherapeutic actions upon NIR photoactivation for photothermal and photodynamic combinational immunotherapy of cancer are then summarized. A conclusion and discussion of the existing challenges and further perspectives for the development and clinical translation of NIR photoactivatable immunomodulatory nanoparticles are finally given.

Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy.

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can remotely generate singlet oxygen (1O2) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPNpro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.

Polymer-based hydrogels with local drug release for cancer immunotherapy.

Immunotherapy that boosts the body's immune system to treat local and distant metastatic tumors has offered a new treatment option for cancer. However, cancer immunotherapy via systemic administration of immunotherapeutic agents often has two major issues of limited immune responses and potential immune-related adverse events in the clinic. Hydrogels, a class of three-dimensional network biomaterials with unique porous structures can achieve local delivery of drugs into tumors to trigger the antitumor immunity, resulting in amplified immunotherapy at lower dosages. In this review, we summarize the recent development of polymer-based hydrogels as drug release systems for local delivery of various immunotherapeutic agents for cancer immunotherapy. The constructions of polymer-based hydrogels and their local delivery of various drugs in tumors to achieve sole immunotherapy, and chemotherapy-, and phototherapy-combinational immunotherapy are introduced. Furthermore, a brief conclusion is given and existing challenges and further perspectives of polymer-based hydrogels for cancer immunotherapy are discussed.

Second Near-Infrared Photothermal Semiconducting Polymer Nanoadjuvant for Enhanced Cancer Immunotherapy.

Immunotherapy has offered new treatment options for cancer; however, the therapeutic benefits are often modest and desired to be improved. A semiconducting polymer nanoadjuvant (SPNII R) with a photothermally triggered cargo release for second near-infrared (NIR-II) photothermal immunotherapy is reported here. SPNII R consists of a semiconducting polymer nanoparticle core as an NIR-II photothermal converter, which is doped with a toll-like receptor (TLR) agonist as an immunotherapy adjuvant and coated with a thermally responsive lipid shell. Upon NIR-II photoirradiation, SPNII R effectively generates heat not only to ablate tumors and induce immunogenic cell death (ICD), but also to melt the lipid layers for on-demand release of the TLR agonist. The combination of ICD and activation of TLR7/TLR8 enhances the maturation of dendritic cells, which amplifies anti-tumor immune responses. Thus, a single treatment of SPNII R-mediated NIR-II photothermal immunotherapy effectively inhibits growth of both primary and distant tumors and eliminates lung metastasis in a murine mouse model. This study thus provides a remote-controlled smart delivery system to synergize photomedicine with immunotherapy for enhanced cancer treatment.

Efficient extraction and purification of benzo[c]phenanthridine alkaloids from Macleaya cordata (Willd) R. Br. by combination of ultrahigh pressure extraction and pH-zone-refining counter-current chromatography with anti-breast cancer activity in vitro.

INTRODUCTION: Macleaya cordata (Willd) R. Br. (Papaveraceae family) is a well-known traditional Chinese medicine used to treat muscle pain, inflamed wounds, and bee bites. Benzo[c]phenanthridine alkaloids are the main active ingredients in M. cordata. In this work, sanguinarine and chelerythrine were efficiently extracted and purified by ultrahigh-pressure extraction (UHPE) technique and pH-zone-refining counter-current chromatography (PZRCCC) from M. cordata. OBJECTIVE: To develop an efficient UHPE method followed by an efficient separation technique using PZRCCC for benzo[c]phenanthridine alkaloids from the study plant species, and to evaluate the study samples for anti-breast cancer activity. METHODOLOGY: The optimal extraction conditions were optimised as extraction pressure 200 MPa, extraction solvent 95% ethanol, solid-liquid ratio 1:30 (g/mL) and extraction time 2 min. A two-phase n-hexane/ethyl acetate/i-propanol/water (1:3:1.5:4.5, v/v) solvent system was optimised with 10 mmol triethylamine in the upper phase and 10 mmol trifluoroacetic acid in lower phase in PZRCCC. The sample loading was optimised as 2.50 g. Moreover, the samples were evaluated for anti-breast cancer activity later on. RESULTS: The 2.50 g sample loading yielded 0.45 g of sanguinarine and 0.59 g chelerythrine in one-step separation using PZRCCC. The anti-breast cancer activities of sanguinarine and chelerythrine were found stronger than positive control (vincristine 5.04 µg/mL) with half-maximal inhibitory concentration values of 0.96 and 3.00 µg/mL, respectively. CONCLUSION: This study showed that the established methods were efficient in extraction (UHPE) and separation (PZRCCC) of the sanguinarine and chelerythrine from M. cordata.

Palladium-based nanomaterials for cancer imaging and therapy.

In recent decade, palladium-based (Pd-based) nanomaterials have shown significant potential for biomedical applications because of their unique optical properties, excellent biocompatibility and high stability in physiological environment. Compared with other intensively studied noble nanomaterials, such as gold (Au) and silver (Ag) nanomaterials, research on Pd-based nanomaterials started late, but the distinctive features, such as high photothermal conversion efficiency and high photothermal stability, have made them getting great attention in the field of nanomedicine. The goal of this review is to provide a comprehensive and critical perspective on the recent progress of Pd-based nanomaterials as imaging contrast agents and therapeutic agents. The imaging section focuses on applications in photoacoustic (PA) imaging, single-photon emission computed tomography (SPECT) imaging, computed tomography (CT) imaging and magnetic resonance (MR) imaging. For treatment of cancer, single photothermal therapy (PTT) and PTT combined with other therapeutic modalities will be discussed. Finally, the safety concerns, forthcoming challenges and perspective of Pd-based nanomaterials on biomedical applications will be presented.

Near-infrared photoresponsive drug delivery nanosystems for cancer photo-chemotherapy.

Drug delivery systems (DDSs) based on nanomaterials have shown a promise for cancer chemotherapy; however, it remains a great challenge to localize on-demand release of anticancer drugs in tumor tissues to improve therapeutic effects and minimize the side effects. In this regard, photoresponsive DDSs that employ light as an external stimulus can offer a precise spatiotemporal control of drug release at desired sites of interest. Most photoresponsive DDSs are only responsive to ultraviolet-visible light that shows phototoxicity and/or shallow tissue penetration depth, and thereby their applications are greatly restricted. To address these issues, near-infrared (NIR) photoresponsive DDSs have been developed. In this review, the development of NIR photoresponsive DDSs in last several years for cancer photo-chemotherapy are summarized. They can achieve on-demand release of drugs into tumors of living animals through photothermal, photodynamic, and photoconversion mechanisms, affording obviously amplified therapeutic effects in synergy with phototherapy. Finally, the existing challenges and further perspectives on the development of NIR photoresponsive DDSs and their clinical translation are discussed.

Near-infrared photothermal liposomal nanoantagonists for amplified cancer photodynamic therapy.

Photodynamic therapy (PDT) has been demonstrated to be a promising strategy for the treatment of cancer, while its therapeutic efficacy is often compromised due to excessive concentrations of glutathione (GSH) as a reactive oxygen species (ROS) scavenger in cancer cells. Herein, we report the development of near-infrared (NIR) photothermal liposomal nanoantagonists (PLNAs) for amplified PDT through through the reduction of intracellular GSH biosynthesis. Such PLNAs were constructed via encapsulating a photosensitizer, indocyanine green (ICG) and a GSH synthesis antagonist, l-buthionine sulfoximine (BSO) into a thermal responsive liposome. Under NIR laser irradiation at 808 nm, PLNAs generate mild heat via a ICG-mediated photothermal conversion effect, which leads to the destruction of thermal responsive liposomes for a controlled release of BSO in a tumor microenvironment, ultimately reducing GSH levels. This amplifies intracellular oxidative stresses and thus synergizes with PDT to afford an enhanced therapeutic efficacy. Both in vitro and in vivo data verify that PLNA-mediated phototherapy has an at least 2-fold higher efficacy in killing cancer cells and inhibiting tumor growth compared to sole PDT. This study thus demonstrates a NIR photothermal drug delivery nanosystem for amplified photomedicine.

Transformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy.

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.

Semiconducting Polymer Nanomaterials as Near-Infrared Photoactivatable Protherapeutics for Cancer.

Cancer therapy is routinely performed in the clinic to cure cancer and control its progression, wherein therapeutic agents are generally used. To reduce side effects, protherapeutic agents that can be activated by overexpressed cancer biomarkers are under development. However, these agents still face certain extent of off-target activation in normal tissues, stimulating the interest to design external-stimuli activatable protherapeutics. In this regard, photoactivatable protherapeutic agents have been utilized for cancer treatments. However, because of the intrinsic features of photolabile moieties, most photoactivatable protherapeutic agents only respond to ultraviolet-visible light, limiting their in vivo applications. Thus, protherapeutic agents that can be activated by near-infrared (NIR) light with minimal phototoxicity and increased tissue penetration are highly desired.In this Account, we summarize our semiconducting polymer nanomaterials (SPNs) as NIR photoactivatable protherapeutic agents for cancer treatment. SPNs are transformed from π-conjugated polymers that efficiently convert NIR light into heat or singlet oxygen (1O2). With photothermal and photodynamic properties, SPNs can be directly used as photomedicine or serve as light transducers to activate heat or 1O2-responsive protherapeutic agents.The heat-activatable SPN-based protherapeutic agents are developed by loading or conjugating of SPNs with therapeutic agents (e.g., agonist, gene, and enzyme). For instance, photothermally triggered release of agonists specifically activates certain protein ion channels on the cellular membrane, leading to ion overinflux induced mitochondria dysfunction and consequently apoptosis of cancer cells. Moreover, photothermal activation of temperature-sensitive bromelain can promote the in situ degradation of collagens (the major components of extracellular matrix), resulting in an improved accumulation of agents in tumor tissues and thus amplified therapeutic outcome.The 1O2-activatable SPN-based protherapeutic agents are constructed through covalent conjugation of SPNs with caged therapeutic agents via hypoxia- or 1O2-cleavable linkers. Upon NIR photoirradiation, SPNs consume oxygen to generate 1O2, which leads to photodynamic therapy (PDT), and meanwhile breaks hypoxia- or 1O2-cleavable linkers for on-demand release and in situ activation of caged protherapeutic molecules (e.g., chemodrug, enzyme, and inhibitor). Such remote activation of SPN-based protherapeutic agents can be applied to induce DNA damage, ribonucleic acid degradation, inhibition of protein biosynthesis, or immune system activation in tumors of living animals. By synergizing PDT with NIR photoactivation of those biological actions, these protherapeutic agents effectively eliminate tumors and even fully inhibit tumor metastasis.This Account highlights the potential of SPNs for construction of versatile NIR photoactivatable protherapeutics to treat cancer at designated times and locations with high therapeutic outcome and precision.

A trustworthy CpG nanoplatform for highly safe and efficient cancer photothermal combined immunotherapy.

Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm-2). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.

Organic Semiconducting Pro-nanostimulants for Near-Infrared Photoactivatable Cancer Immunotherapy.

In this study, an organic semiconducting pro-nanostimulant (OSPS) with a near-infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises a semiconducting polymer nanoparticle (SPN) core and an immunostimulant conjugated through a singlet oxygen (1 O2 ) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and 1 O2 to exert combinational phototherapy not only to ablate tumors but also to produce tumor-associated antigens. More importantly, NIR irradiation triggers the cleavage of 1 O2 -cleavable linkers, triggering the remote release of the immunostimulants from OSPS to modulate the immunosuppressive tumor microenvironment. Thus, the released tumor-associated antigens in conjunction with activated immunostimulants induce a synergistic antitumor immune response after OSPS-mediated phototherapy, resulting in the inhibited growth of both primary/distant tumors and lung metastasis in a mouse xenograft model, which is not observed for sole phototherapy.