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Abstract Background HyBryteTM is a photodynamic therapy of topical hypericin that has recently been shown to be safe and efficacious in early stage cutaneous T‐cell lymphoma (CTCL). However, its efficacy, absorption, and effect on heart function parameters in patients who require greater HyBryteTM exposure is unknown. Objectives The primary objectives in this study were to assess hypericin blood levels using a validated detection method with a cut‐off value of 0.05 ng/mL and to determine if topical HyBryteTM induces any electrocardiogram (EKG) changes during 8 weeks of treatment. A secondary endpoint of this study was to assess the effectiveness of HyBryteTM in this patient population as well as assessing a different additional light device than the one used in the Phase 3 HPN‐CTCL‐01/fluorescent light activated synthetic hypericin trial also entitled “A phase 3 multicenter randomised placebo‐controlled study to determine the efficacy of topical hypericin and light irradiation for the treatment of cutaneous T‐cell lymphoma”. Methods A confirmatory, prospective, open‐label, single‐centre, interventional study focused on stage IB and IIA mycosis fungoides with more than 10% of their body surface areas involved was performed. Results Hypericin concentration in K2EDTA whole blood samples collected before and after light activation at Weeks 4, 6 and 8 showed an average blood concentration of 0.13 ng/mL and achieved steady state by Week 4. EKGs were examined for clinical changes at each study visit, including changes in QT intervals and correction of heart rates. No significant clinical changes in EKGs were observed. Conclusions Hypericin does not appear to be significantly absorbed through the skin nor cause significant cardiac changes overall or prolong the QT interval when applied topically. A larger study is necessary to clearly define these results.

Abstract Background Photodynamic therapy (PDT) is an antitumor therapy and has traditionally been regarded as a localized therapy in itself. However, recent reports have shown that it not only exerts a direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized that the immunological response induced by PDT could potentially enhance the efficacy of programmed death‐1 (PD‐1) / programmed death‐ligand 1 (PD‐L1) blockade. Methods The cytotoxic effects of PDT on colon 26 cells were investigated in vitro using the WST assay. We investigated whether the antitumor effect of anti‐PD‐1 antibodies could be amplified by the addition of PDT. We performed combination therapy by randomly allocating tumor‐bearing mice to four treatment groups: control, anti‐PD‐1 antibodies, PDT, and a combination of anti‐PD‐1 antibodies and PDT. To analyze the tumor microenvironment after treatment, the tumors were resected and pathologically evaluated. Results The viability rate of colon 26 cells decreased proportionally with the laser dose. In vivo experiments for combined PDT and anti‐PD‐1 antibody treatment, combination therapy showed an enhanced antitumor effect compared with the control. Immunohistochemical findings of the tumor microenvironment 10 days after PDT indicated that the number of CD8+ cells, the area of Iba‐1+ cells and the area expressing PD‐L1 were significantly higher in tumors treated with combination therapy than in tumors treated with anti‐PD‐1 antibody alone, PDT alone, or the control. Conclusions PDT increased immune cell infiltration into the tumor microenvironment. The immunological response induced by PDT may enhance the efficacy of PD‐1/PD‐L1 blockade.

Abstract Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age‐related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge. A β‐galactosidase (β‐gal)‐activated boron dipyrromethene (BODIPY)‐based photosensitizer (compound 1) is reported here that can selectively detect and eradicate senescent cells. It contains a galactose moiety connected to a pyridinium BODIPY via a self‐immolative nitrophenylene linker, of which the photoactivity is effectively quenched. Upon interactions with the senescence‐associated β‐gal, it undergoes enzymatic hydrolysis followed by self‐immolation, leading to the release of an activated BODIPY moiety by which the fluorescence emission and singlet oxygen generation are restored. The ability of 1 to detect and eliminate senescent cells is demonstrated in vitro and in vivo, using SK‐Mel‐103 tumor‐bearing mice treated with senescence‐inducing therapy. The results demonstrate that 1 can be selectively activated in senescent cells to trigger a robust senolytic effect upon irradiation. This study breaks new ground in the design and application of new senolytic agents based on photodynamic therapy.

Abstract Multi‐drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH‐sensitive photosensitizer‐drug conjugates (CyR‐SS‐L) are designed and synthesized. CyR‐SS‐L localized in the mitochondria then is cleaved into CyR‐SG and SG‐L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR‐SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG‐L part is used for chemotherapy. CyR‐SS‐L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR‐SS‐L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

Abstract Dyes have conventionally been used in medicine for staining cells, tissues, and organelles. Since these compounds are also known as photosensitizers (PSs) which exhibit photoresponsivity upon photon illumination, there is a high desire towards formulating these molecules into nanoparticles (NPs) to achieve improved delivery efficiency and enhanced stability for novel imaging and therapeutic applications. Furthermore, it has been shown that some of the photophysical properties of these molecules can be altered upon NP formation thereby playing a major role in the outcome of their application. In this review, we primarily focus on introducing dye categories, their formulation strategies and how these strategies affect their photophysical properties in the context of photothermal and non‐photothermal applications. More specifically, the most recent progress showing the potential of dye supramolecular assemblies in modalities such as photoacoustic and fluorescence imaging, photothermal and photodynamic therapies as well as their employment in photoablation as a novel modality will be outlined. Aside from their photophysical activity, we delve shortly into the emerging application of dyes as drug stabilizing agents where these molecules are used together with aggregator molecules to form stable nanoparticles.

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

Abstract The escalating spread of drug‐resistant bacteria and viruses is a grave concern for global health. Nucleic acids dominate the drug‐resistance and transmission of pathogenic microbes. Here, imidazolium‐type poly(ionic liquid)/porphyrin (PIL‐P) based electrospun nanofibrous membrane and its cerium (IV) ion complex (PIL‐P‐Ce) are developed. The obtained PIL‐P‐Ce membrane exhibits high and stable efficiency in eradicating various microorganisms (bacteria, fungi, and viruses) and decomposing microbial antibiotic resistance genes and viral nucleic acids under light. The nuclease‐mimetic and photocatalytic mechanisms of the PIL‐P‐Ce are elucidated. Co‐infection wound models in mice with methicillin‐resistant S. aureus and hepatitis B virus demonstrate that PIL‐P‐Ce integrate the triple effects of cationic polymer, photocatalysis, and nuclease‐mimetic activities. As revealed by proteomic analysis, PIL‐P‐Ce shows minimal phototoxicity to normal tissues. Hence, PIL‐P‐Ce has potential as a “green” wound dressing to curb the spread of drug‐resistant bacteria and viruses in clinical settings.

Abstract Phototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water‐soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal‐to‐liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.

Abstract Lipid droplets (LDs), which are the hubs of lipid metabolism, play a critical role in maintaining cellular energy homeostasis. The construction of advanced photosensitizers (PSs) capable of manipulating LD‐mediated cell fate regulation is highly desirable though rarely reported. In this study, a near‐infrared emissive PS (DPCMP) with LDs specificity was synthesized and successfully applied to induce ferroptosis and apoptosis. DPCMP exhibited typical aggregation‐induced emission characteristics owing to its twisted molecular conformation. Excellent biocompatibility and suitable lipophilicity allowed DPCMP to specifically stain the LDs in living cells. Under white light illumination, the DPCMP displayed potent reactive oxygen species (ROS) generation capacity through both type I and II photochemistry. The massive accumulation of lethal ROS generated by DPCMP‐mediated photosensitization initiated lipid peroxidation, impaired cellular redox homeostasis, and led to endoplasmic reticulum oxidative stress, ultimately inhibiting cellular proliferation via concurrent ferroptosis and apoptosis in both living cancer cells and multicellular tumor spheroids.

Abstract Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor‐suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold‐responsive nanoplatform composed of upconversion nanoparticles coated with silica – chlorin e6 – hyaluronic acid (UCNPs@SiO2‐Ce6‐HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low‐temperature treatment afforded a 2.45‐fold enhancement in the luminescence of UCNPs and a 3.15‐fold increase in the photodynamic efficacy of UCNPs@SiO2‐Ce6‐HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA‐mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2‐Ce6‐HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo‐PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Abstract Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is nearly universal even after surgery, chemotherapy, and radiation. Photodynamic therapy (PDT) involves photosensitizer administration followed by light activation to generate reactive oxygen species at tumor sites, thereby killing cells or inducing biological changes. PDT can ablate unresectable GBM and sensitize tumors to chemotherapy. Verteporfin (VP) is a promising photosensitizer that relies on liposomal carriers for clinical use. While lipids increase VP's solubility, they also reduce intracellular photosensitizer accumulation. Here, a pure‐drug nanoformulation of VP, termed “NanoVP”, eliminating the need for lipids, excipients, or stabilizers is reported. NanoVP has a tunable size (65–150 nm) and 1500‐fold higher photosensitizer loading capacity than liposomal VP. NanoVP shows a 2‐fold increase in photosensitizer uptake and superior PDT efficacy in GBM cells compared to liposomal VP. In mouse models, NanoVP‐PDT improved tumor control and extended animal survival, outperforming liposomal VP and 5‐aminolevulinic acid (5‐ALA). Moreover, low‐dose NanoVP‐PDT can safely open the blood‐brain barrier, increasing drug accumulation in rat brains by 5.5‐fold compared to 5‐ALA. NanoVP is a new photosensitizer formulation that has the potential to facilitate PDT for the treatment of GBM.

Abstract We describe a case of gastric cancer treated by photodynamic therapy (PDT) with talaporfin sodium using a novel simultaneous light‐emitting method. An 82‐year‐old man was diagnosed with gastric cancer near the cardia with suspected deep submucosal invasion. Surgical resection was deemed high‐risk owing to an underlying pulmonary disease. After ruling out endoscopic procedures due to intense fibrosis resulting from the scarring, PDT with talaporfin sodium was chosen. PDT was successfully conducted using an endoscope with simultaneous light emission. The patient experienced a complete response to the treatment and showed no signs of recurrence during follow‐up. This case highlights the potential of PDT with talaporfin sodium as a viable alternative for challenging cases, particularly in patients unsuitable for surgery and endoscopic resection. Furthermore, the novel simultaneous light‐emitting method may improve the efficiency of the procedure. This case demonstrates the potential of PDT in gastric cancer treatment, especially for high‐risk patients.

Abstract Hydrogen‐bonded organic frameworks (HOFs) are crystalline porous materials with permanent voids formed via self‐assembly of organic molecules through hydrogen bonding and intermolecular forces. Further combination of HOFs with functional material would broaden their application horizon but were less explored in existing literature. Herein, a highly porous and photosensitive HOF was successfully coated onto upconversion nanoparticles (UCNPs) to construct a core–shell structure named UNCPs@PFC‐73‐Ni. To enhance spectral overlap and maximize energy conversion efficiency, this study utilized the Er and Tm co‐doped UCNPs, which can effectively convert infrared light into visible light emission thereby exciting the porphyrin shell. Subsequent investigation reveals that the composite exhibits significant photodynamic and photothermal effects under infrared light. Encouraged by its noticeable photoactivity, UCNPs@PFC‐73‐Ni was evaluated as an antibacterial agent against Escherichia coli. Notably, significant antibacterial efficacy was observed, highlighting the potential of UCNPs@PFC‐73‐Ni as an effective antibacterial agent under infrared light irradiation.

Abstract The development of efficient drug delivery systems is essential for improving the efficacy and safety of cancer drugs, particularly for aggressive and difficult‐to‐treat cancers. Covalent organic frameworks (COFs) are emerging as innovative porous nanomaterials in drug delivery systems (DDS), due to their unique properties, including the metal‐free organic skeleton, predetermined structures and pore geometries, high porosity, large surface area, facile surface modification potential, and good biocompatibility. These characteristics make COFs excellent candidates for improving drug delivery by enhancing drug loading capacity and enabling precise encapsulation. This review emphasizes the importance of donor‐acceptor‐based COFs, which provide channels for charge transportation, and we also explore how the π‐conjugated skeleton of COFs enhances its long‐acting fluorescent properties and facilitates drug uptake via cell endocytosis. While this review primarily focuses on recent advancements in COF‐based targeted DDS, it also acknowledges the challenges posed by the diverse pore geometries in porous materials and discusses potential solutions. Further, it underlines the potential of developing future drug carriers that can successfully and specifically target cancer cells, improving treatment efficiency while reducing adverse side effects.

Abstract Photodynamic therapy (PDT) is a minimally invasive and controllable local cancer treatment for cholangiocarcinoma (CCA). However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS‐responsive liposomes encapsulating the photosensitizer Ce6, the NO gas‐generating agent L‐arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti‐tumor function of cytotoxic T lymphocytes through the downregulation of PD‐L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid‐derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.

Abstract Photodynamic therapy (PDT) is a novel therapy that combines photosensitizers, light, and oxygen molecules to treat diseases such as joint lesions and microbial infections through photodynamic reactions. The photosensitizers are activated under specific wavelengths of laser radiation to generate reactive oxygen species, which alter the microenvironment of the diseased tissue, cause ischemia and target cell death, and thus effectively treat cancer. Now that there is growing evidence that nonlethal doses of PDT reduce inflammation and treat infections in multiple animal models of arthritis, PDT should be considered as a new option for the treatment of arthritis. This article presents a literature review of published original articles and review articles concerning photodynamic therapy and arthritis. We conducted a comprehensive literature search in PubMed, Web of Science and Google Scholar databases, excluding duplicated and irrelevant studies. In cases of duplicated research, we selected articles with higher impact factors for the review. In this review, we summarize the application and progress of PDT in the treatment of rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and infectious arthritis, and clarify the advantages and limitations of PDT for arthritis. PDT offers therapeutic value for patients with inflammatory and infectious arthritis through promoting vascular occlusion, cell death, and antibacterial therapy.

Abstract Arthritis is a chronic disease whose etiology is difficult to pinpoint, and the difficulty of arthritis detection and subsequent treatment causes enormous distress to patients. In recent years, thanks to advances in medicine and detection, a variety of treatment modalities for arthritis have emerged. The combination of emerging detection technologies with different anti‐inflammatory medications and even advances in surgical techniques have all played a positive role in the treatment of arthritis. In the present work, we have collected relevant literature on fluorescence (FL) imaging and phototherapy of arthritis in recent years, intending to reveal the advantages and potential application value of FL imaging and phototherapy for researchers. Meanwhile, due to the shortcomings of FL imaging and phototherapy in the diagnosis and treatment of arthritis, we advocate overcoming these difficulties in future research.

Abstract Background Photodynamic therapy (PDT) using photosensitisers is a minimally invasive treatment for malignant tumours. However, ideal photosensitisers are not yet established. Recently, we developed a new photosensitiser, glucose‐conjugated chlorin e6 (G‐Ce6). Objectives To evaluate the clinical efficacy of vascular‐targeted PDT (VTP), a type of PDT utilising a short drug‐light interval, using G‐Ce6 to treat spontaneously occurring tumours in dogs. Methods Five dogs with spontaneously occurring tumours (malignant melanoma: three; haemangiopericytoma: two; and squamous cell carcinoma: one) were subjected to VTP. These dogs were intravenously injected with G‐Ce6 at doses of 1–3 mg/kg 5 min before laser irradiation. Tumours were superficially or interstitially irradiated using a 677‐nm diode laser. Results Repeated VTP decreased tumour size, yielding complete remission in three dogs. Complications such as oedema surrounding normal tissues and fistulae were observed, and the oedema was self‐limiting. The fistula was cured by debriding the necrotic tissues formed after VTP. Conclusions Our findings demonstrate that VTP using G‐Ce6 had antitumour effects in dogs with spontaneously occurring tumours.

Abstract Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long‐lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long‐lasting abscopal effect.

Abstract Glutathione (GSH)‐activated prodrugs are promising for overcoming the limitations of conventional anti‐tumor drugs. However, current GSH‐responsive disulfide groups exhibit unregulated reactivity, making it impossible to precisely control the drug release rate. We herein report a series of GSH‐responsive prodrugs with a “three‐in‐one” molecular design by integrating a fluorescence report unit, stimuli‐responsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution (SNAr) reactivity. The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron‐withdrawing or ‐donating abilities on the BODIPY core. Furthermore, the prodrugs self‐assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy (PDT). The PDT process also increases the concentration of GSH in cells, further promoting the release of drugs for chemotherapy. This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.

Abstract Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single‐component dual‐functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)‐generated HOCl. A representative prodrug (DHU‐CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU‐CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU‐CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase‐2 (COX‐2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX‐2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU‐CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single‐component dual‐functional prodrug activated by TME‐specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX‐2 inhibitor.

Abstract For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di‐iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin‐1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome‐deliver Liproxstatin‐1 effectively inhibits the ferroptosis of tumor neutrophils. LLI‐based immunogenic PDT and neutrophil‐targeting immunotherapy synergistically boost the anti‐PD‐1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy.

Abstract As an effective and non‐invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber‐optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post‐PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black‐hole quencher BHQ‐3 conjugated with a bicyclo[6.1.0]non‐4‐yne (BCN) moiety and a tetrazine‐substituted boron dipyrromethene‐based photosensitizer. By using tumor‐bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ‐3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT.

Abstract Glioma is one of the most common malignant tumors of the central nervous system, leading high mortality rates in human. Aggregation‐induced emission (AIE) photosensitizers‐based photodynamic therapy (PDT) has emerged as a promising therapeutic strategy for least‐invasive treatment of glioma, which involves local irradiation of the tumor using an external near‐infrared (NIR) laser. Unfortunately, most AIE photosensitizers suffered from poorly penetration of the visible light excitation, bad spatiotemporal resolution in deep tissues and low efficient blood‐brain barrier (BBB) crossing ability, which greatly limited the clinical practice of AIE photosensitizers for especially deep‐seated brain tumor treatment. In this work, we developed a multifunctional NIR‐driven theranostic agent through hybrid of AIE photosensitizers TIND with rare‐earth doping nanoparticles (RENPs) NaGdF4:Nd/Yb/Tm with up/down dual‐mode conversion luminescence. The theranostic agent was further decorated with D‐type neuropeptide DNPY for crossing BBB and targeting glioma. Under the 808‐nm light irradiation, the down‐conversion NIR‐II luminescence could indicate the position glioma and the upconversion NIR‐I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ. These results demonstrate that the integration of D‐type neuropeptide, AIE photosensitizers and RENPs could be promising candidates for in vivo NIR‐II fluorescence image‐guided through‐skull PDT treatments of brain tumors.

Abstract Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited‐state properties. Herein, a synthetic approach for attaching aryl substituents at the C2’ position of the thio‐pentamethine cyanine (TCy5) dye structure is reported for the first time. C2’‐aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase‐activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2’‐aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.

Abstract Deep NIR organic phototheranostic molecules generally have large π‐conjugation structures and show highly hydrophobic properties, thus, forming strong π–π stacking in the aqueous medium, which will affect the phototheranostic performance. Herein, an end‐group strategy is developed to lift the performance of NIR‐II emitting photosensitizers. Extensive characterizations reveal that the hydrogen‐bonding interactions of the hydroxyl end group can induce a more intense π–π electronic coupling than the chlorination‐mediated intermolecular forces. The results disclose that π–π stacking will lower fluorescence quantum yield but significantly benefit the photodynamic therapy (PDT) efficiency. Accordingly, an asymmetrically substituted derivative (BTIC‐δOH‐2Cl) is developed, which shows balanced phototheranostic properties with excellent PDT efficiency (14.6 folds of ICG) and high NIR‐II fluorescence yield (2.27%). It proves the validity of the end‐group strategy on controlling the π–π interactions and rational tuning the performance of NIR‐II organic phototheranostic agents.

Abstract Mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor, accounting for 0.2% of all lung tumors. The standard treatment for MEC of the primary bronchus is surgery, although intraluminal bronchoscopic treatment has recently become an option. A 68‐year‐old man presented with an asymptomatic bronchial tumor in the right intermediate bronchus. The tumor was resected using a high‐frequency snare (HFS) during bronchoscopy, and the specimen was pathologically diagnosed as low‐grade MEC. A residual lesion was detected in the resected area by autofluorescence imaging. The tumor appeared to be localized within the subepithelial layer without metastases, and photodynamic therapy (PDT) was performed as a local treatment. The patient had no recurrence for 18 months. PDT is effective and safe for patients with centrally located early‐stage lung cancer, but there are few reports of its use for rare tumors, such as MEC. In this case, PDT allowed for local control and avoided surgery, including bronchoplasty, for MEC. Combined treatment of tumor reduction by HFS and PDT of the residual lesion may be an optimal treatment for MEC of the bronchus.

Abstract Photocyclization is demonstrated as a powerful tool for building complicated polycyclic molecules. And efficient photocyclization is competent as an artful strategy to develop photo‐responsive smart materials. Herein, an efficient free radical‐mediated photocyclization for triphenylphosphindole oxide (TPPIO) derivatives to generate tribenzophosphindole oxide (TBPIO) derivatives at ambient condition is reported. The reaction mechanism and substituent effect on photocyclization efficiency are thoroughly investigated. Additionally, photophysical and photochemical properties of TPPIO and TBPIO derivatives are measured for comparison and deeply deciphered by theoretical calculation. TPPIO derivatives own typical aggregation‐induced emission feature but barely generate reactive oxygen species (ROS), while TBPIO derivatives experience aggregation‐caused quenching but show efficient Type I ROS generation capacity. Further, in vitro experiments demonstrate that this photo‐conversion can efficiently occur in situ in living cells to activate photodynamic therapy (PDT) effect to trigger lipid peroxidation with selective fluorescence “light up” in lipid droplet area under continuous irradiation. This work extends the optoelectronically and biologically interesting phosphindole oxide‐containing π‐conjugated systems through an efficient synthetic strategy, provides in‐depth mechanistic descriptions in the aspects of reaction and property, and further presents their great potentials for photoactivated and self‐reported PDT.

Abstract 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.

Abstract Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP‐QY has a high molar absorption coefficient and an excellent ability to generate 1O2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP‐QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP‐QY‐mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole‐resistant strains. Moreover, TBTCP‐QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.

Abstract Although molybdenum trioxide nanomaterials have been widely explored as nanoagents for biomedical applications against bacteria through photothermal therapy, chemodynamic therapy, and catalytic therapy, their utilization as photosensitizers for photodynamic therapy (PDT) have been rarely reported so far. Herein, we report the activation of MoO3 nanobelts via aqueous co‐intercalation of Na+ and H2O into their van der Waals gaps as a near‐infrared Type I photosensitizer for photodynamic periodontitis treatment. The Na+/H2O intercalation of MoO3 nanobelts can shorten its length, generate rich oxygen vacancies, and enlarge its interlayer gaps. Such structural changes thus can induce the color change from white to dark blue with a strong near‐infrared (NIR) absorption. When used as a photosensitizer, the I‐MoO3−x nanobelts exhibit much higher activities for the generation of superoxide radical (·O2−) under an 808 nm laser irradiation than that of the pristine MoO3 nanobelts. Therefore, the prepared I‐MoO3−x nanobelts show a spectral antibacterial activity against Escherichia coli and Saccharomyces aureus, thus yielding a good clinical therapeutic effect on periodontitis. Our study proves that aqueous intercalation can be a simple but powerful strategy to activate layered MoO3 nanomaterials for high‐performance PDT.

Abstract Choroidal neovascularization (CNV) is the key pathological event of wet age‐related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti‐angiogenic therapy with anti‐vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti‐angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less‐invasive approach is reported to achieve anti‐angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di‐DAS‐VER NPs). The nanosystem is self‐assembled by reactive oxygen species (ROS)‐sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red‐light irradiation to the diseased eyes, intraocular release of anti‐angiogenic DAS is observed, together with selective neo‐vessels occlusion by VER‐generated ROS. Notably, Di‐DAS‐VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.

Abstract Metal–organic framework (MOF)‐based drug delivery systems have demonstrated values in oncotherapy. Current research endeavors are centralized on the functionality enrichment of featured MOF materials with designed versatility for synergistic multimodal treatments. Here, inspired by the multifarious biological functions including ferroptosis pattern, porphyrins, and cancer cell membrane (CCM) camouflage technique, novel multi‐biomimetic MOF nanocarriers from microfluidics are prepared. The Fe3+, meso‐tetra(4‐carboxyphenyl)porphine and oxaliplatin prodrug are incorporated into one MOF nano‐system (named FeTPt), which is further cloaked by CCM to obtain a “Trojan Horse”‐like vehicle (FeTPt@CCM). Owing to the functionalization with CCM, FeTPt@CCM can target and accumulate at the tumor site via homologous binding. After being internalized by cancer cells, FeTPt@CCM can be activated by a Fenton‐like reaction as well as a redox reaction between Fe3+ and glutathione and hydrogen peroxide to generate hydroxyl radical and oxygen. Thus, the nano‐platform effectively initiates ferroptosis and improves photodynamic therapy performance. Along with the Pt‐drug chemotherapy, the nano‐platform exhibits synergistic multimodal actions for inhibiting cancer cell proliferation in vitro and suppressing tumor growth in vivo. These features indicate that such a versatile biomimetic MOF delivery system from microfluidics has great potential for synergistic cancer treatment.

Abstract Photodynamic therapy is becoming increasingly popular for combat of bacteria. In the clinical photodynamic combat of bacteria, one critical issue is to avoid the potential damage to the host since the reactive oxygen species produced by photosensitizers are also harmful to mammalian cells. In this work, we report an aggregation‐induced‐emission‐active bacterial inhibitor and photosensitizer, OEO‐TPE‐MEM (OTM), for the imaging, killing, and light‐enhanced inactivation of bacteria. OTM could efficiently bind to and kill Gram‐positive bacteria, while its affinity to Gram‐negative bacteria is lower, and a higher OTM concentration is required for killing Gram‐negative bacteria. OTM is also an efficient photosensitizer and could efficiently sensitize the production of reactive oxygen species, which enhances its killing effect on both Gram‐positive and Gram‐negative bacteria. More interestingly, OTM is very biocompatible with normal mammalian cells both in the dark and under light irradiation. OTM in mice models with bacteria‐infected wounds could promote the healing of infected wounds without affecting their organs and blood parameters, which makes it an excellent candidate for clinical applications.

Abstract Background Photodynamic therapy (PDT) is a cancer‐targeted treatment that uses a photosensitizer (PS) and laser irradiation. The effectiveness of current PDT using red light for advanced cancers is limited, because red light can only reach depths within a few millimeters. To enhance the antitumor effect for lung cancers, we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin and a PS, mono‐L‐aspartyl chlorin e6 (NPe6). Methods We examined whether cetuximab encapsulated in endosomes was released into the cytosol by PS in PDT under light irradiation. A431 cells were treated with fluorescein isothiocyanate‐labeled cetuximab, NPe6, and light irradiation and were observed with fluorescence microscopy. We analyzed the cytotoxicity of saporin‐conjugated cetuximab (IT‐cetuximab) in A431, A549, and MCF7 cells and the antitumor effect in model A549‐bearing mice in vivo using the iTAP method. Results Fluorescent microscopy analysis showed that the photodynamic effect of NPe6 (20 μM) and light irradiation (37.6 J/cm2) caused the release of cetuximab from the endosome into the cytosol. In vitro analysis demonstrated that the iTAP method enhanced the cytotoxicity of IT‐cetuximab by the photodynamic effect. In in vivo experiments, compared with IT‐cetuximab alone or PDT alone, the iTAP method using a low dose of IT‐cetuximab showed the greatest enhancement of the antitumor effect. Conclusions Our study is the first report of the iTAP method using NPe6 for lung cancer cells. The iTAP method may become a new, minimally invasive treatment superior to current PDT methods.

Abstract X‐ray induced photodynamic therapy (X‐PDT) circumvents the poor penetration depth of conventional PDT with minimal radio‐resistance generation. However, conventional X‐PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation‐induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X‐ray irradiation is reported for hypoxia‐tolerant X‐PDT. Heteroatoms are introduced to enhance X‐ray harvesting and ROS generation ability, and AIE‐active TBDCR exhibits aggregation‐enhanced ROS especially less oxygen‐dependent hydroxyl radical (HO•−, type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near‐infrared fluorescence and massive singlet oxygen and HO•− generation under direct X‐ray irradiation, which demonstrate excellent antitumor X‐PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1O2 and radicals (HO•−) in response to direct X‐ray irradiation, which shall provide new insights for designing organic scintillators with excellent X‐ray harvesting and predominant free radical generation for efficient X‐PDT.

Abstract Intracellular zinc ion (Zn2+) accumulation disrupts the Zn2+ homeostasis, providing an ion‐overloading anticancer strategy with great potential. The self‐adaptation of tumor cells to ion concentration, however, puts forward higher requirements for the design of ion‐overloading strategy. Herein, “block and attack” antitumor strategy was applied through a composite nanomaterials (UHSsPZH NPs). The strategy demonstrated powerful ion interference ability through both “blocking” the efflux of excess Zn2+ via gene silencing and “attacking” tumor cells via target delivery of ZnO2. After cellular internalization, ZnO2 was degraded to Zn2+ and hydrogen peroxide (H2O2), and the gene expression of zinc transporter 1 (ZnT1) was silenced by targeting of released siRNA, which together caused intracellular Zn2+‐overload. Disorder of Zn2+ further interfered with intracellular Ca2+ homeostasis, inhibited the electron transport chain and promoted the production of endogenous reactive oxygen species (ROS), which assisted the “attack” to tumor cells together with the exogenous ROS generated by UHSsPZH NPs under 980 nm laser irradiation. In summary, this work supplies a “block and attack” strategy for the application of ion homeostasis interference in tumor therapy.

Abstract Bacteria can cause numerous infectious diseases and has been a major threat to human humans. Although antibiotics have partially succeeded in treating bacteria, owing to antibiotic abuse, the emergence of multidrug‐resistant (MDR) bacteria has drastically diminished their potency. Since the invention of laser, the combination of light and photosensitizers, photodynamic therapy (PDT), has become an effective noninvasive treatment along with photothermal therapy (PTT), in which heat is generated by nonradiative relaxation. Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection, particularly against MDR bacteria. This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

Abstract Cancer starvation therapy have received continuous attention as an efficient method to fight against wide‐spectrum cancer. However, during cancer starvation therapy, the protective autophagy promotes cancer cells survival, compromising the therapeutic effect. Herein, a novel strategy by combination of autophagy‐activated fluorescent photosensitizers (PSs) and cancer starvation therapy to realize the controllable and efficient ablation of tumor is conceived. Two dual‐emissive self‐reporting aggregation‐induced emission luminogens (AIEgens), TPAQ and TPAP, with autophagy‐activated reactive oxygen species (ROS) generation are prepared to fight against the protective autophagy in cancer starvation therapy. When protective autophagy occurs, a portion of TPAQ and TPAP will translocate from lipid droplets to acidic lysosomes with significant redshift in fluorescence emission and enhanced ROS generation ability. The accumulation of ROS induced by TPAQ‐H and TPAP‐H causes lysosomal membrane permeabilization (LMP), which further results in cell apoptosis and promotes cell death. In addition, TPAQ and TPAP can enable the real‐time self‐reporting to cell autophagy and cell death process by observing the change of red‐emissive fluorescence signals. Particularly, the efficient ablation of tumor via the combination of cancer starvation therapy and photodynamic therapy (PDT) induced by TPAQ has been successfully confirmed in 3D tumor spheroid chip, suggesting the validation of this strategy.

Abstract Cancer stem cell (CSC) has been considered a key driver of tumor growth, recurrence, and metastasis due to its self‐renewal and tumor initiation capacities called stemness. Stemness is also responsible for the high resistance of CSC to current therapeutic strategies, including photodynamic therapy (PDT) and chemotherapy. In this study, a carrier‐free nanodrug (designated as MKCe6 nanoparticle [NP]) self‐assembled by photosensitizer chlorin e6 (Ce6) and stemness inhibitor MK‐0752 was prepared for effective tumor repression. Stemness inhibition caused by MK‐0752 could sensitize CSCs to PDT. Benefiting from the high drug‐loading capacity and efficient cellular internalization, MKCe6 NPs exhibited good performance in PDT and stemness inhibition. In this way, effective tumor growth repression and tumorigenesis inhibition by MKCe6 NPs were observed both in vitro and in vivo. This self‐delivery nanodrug for stemness inhibition‐enhanced photodynamic therapy may provide new insights for clinical cancer therapy.

Abstract Photomediated immunotherapy explored to combine the anti‐cancer effect of phototherapy with the immune enhancement ability of immunotherapy, and shown great prospects for cancer treatment strategies. However, photomediated immunotherapy triggered antitumor immunity through the release of tumor antigens and damage‐associated molecular patterns from necrotic tumor cells was not enough mighty to improve the therapeutic benefits due to the immunosuppressive tumor microenvironments. Herein, a tumor‐targeted nano‐adjuvant Fucoidan@Al(OH)3‐Poly(I:C)/IR‐820 for tumor‐targeted therapy and metastasis inhibition was designed and prepared. The intrinsic immunomodulatory effects of tumor‐targeted nano‐adjuvant and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, were explored. The results proved that the multifunctional nano‐adjuvant combined with photothermal, photodynamic, and immunotherapy could effectively treat breast cancer and had metastasis inhibition effect by enhancing anti‐tumor immunity through immunomodulation, it should have great application potential in the treatment of breast cancer.

Abstract The fact that multidrug resistance (MDR) could induce medical device‐related infections, along with the invalidation of traditional antibiotics has become an intractable global medical issue. Therefore, there is a pressing need for innovative strategies of antibacterial functionalization of medical devices. For this purpose, a multimodal antibacterial coating that combines photothermal and photodynamic therapies (PTT/PDT) is developed here based on novel heavy atom‐free photosensitizer compound, BDP‐6 (a kind of boron‐dipyrromethene). The photothermal conversion efficiency of BDP‐6 is of 55.9%, which could improve biocompatibility during PTT/PDT process by reducing the exciting light power density. Furthermore, BDP‐6, together with oxidized hyaluronic acid, is crosslinked with a natural polymer, gelatin, to fabricate a uniform coating (denoted as polyurethane (PU)‐GHB) on the surface of polyurethane. PU‐GHB has excellent synergistic in vitro PTT/PDT antibacterial performance against both susceptible bacteria and MDR bacteria. The antibacterial mechanisms are revealed as that hyperthermia could reduce the bacterial activity and enhance the permeability of inner membrane to reactive oxygen species by disturbing cell membrane. Meanwhile, in an infected abdominal wall hernia model, the notable anti‐infection performance, good in vivo compatibility, and photoacoustic imaging property of PU‐GHB are verified. A promising strategy of developing multifunctional antibacterial coatings on implanted medical devices is provided here.

Abstract Although the curative effect of hematological malignancies has been improved in recent years, relapse or drug resistance of hematological malignancies will eventually recur. Furthermore, the microenvironment disorder is an important mechanism in the pathogenesis of hematological malignancies. Immunogenic cell death (ICD) is a unique mechanism of regulated cell death (RCD) that triggers an intact antigen‐specific adaptive immune response by firing a set of danger signals or damage‐associated molecular patterns (DAMPs), which is an immunotherapeutic modality with the potential for the treatment of hematological malignancies. This review summarizes the existing knowledge about the induction of ICD in hematological malignancies and the current research on combining ICD inducers with other treatment strategies for hematological malignancies.

Abstract Chemodynamic therapy (CDT) utilizes Fenton and/or Fenton‐like reactions in the tumor microenvironment (TME) to produce cytotoxic reactive oxygen species (ROS, mainly hydroxyl radicals, •OH) for inducing cancer cell death. Since CDT exhibits minimal invasiveness and high tumor specificity by responding to TME (overexpressed hydrogen peroxide (H2O2) and glutathione (GSH) generation), a lot of related research has been conducted recently. Photo‐facilitated CDT can further enhance the catalytic activity and controllability of the treatment. In addition, other photo‐induced therapies, including photodynamic and photothermal therapy (PDT, PTT), may synergize with CDT to obtain boosting treatment efficacy and avoid multidrug resistance. In this minireview, we summarize the recent advances in photo‐assisted CDT, including PTT‐facilitated CDT and PDT‐facilitated CDT. More importantly, the challenges encountered in the treatment process are discussed and potential development directions are suggested to facilitate the clinical translation of photo‐assisted CDT in the future.

Abstract Various nanocarriers have been explored to deliver drugs for combination therapy. However, most nanocarriers are composed of inert materials without contribution for improving the cancer therapeutic effect. Herein, a hydrophobic photosensitizer is conjugated to poly (ethylene glycol) to form an amphiphilic polymer, which further self‐assembles into nanomicelle. The generated nanomicelle can act as a nanocarrier to encapsulate a cytotoxic molecule, IR‐775, for combination therapy. The yielded nanodrug is totally composed of pharmacologically active ingredients to avoid any possible toxicity resulted from carrier materials. The nanodrug performs enhanced therapeutic effect compared with any monotherapy and exhibits negligible hemolysis, indicating good biocompatibility for further in vivo applications.

Abstract Although immunotherapy has achieved recent clinical success in antitumor therapy, it is less effective for solid tumors with large burdens. To overcome this challenge, herein, we report a new strategy based on platelet membrane‐camouflaged aggregation‐induced emission (AIE) luminogen (Plt‐M@P) combined with the anti‐programmed death ligand 1 (anti‐PD‐L1) for tumoral photodynamic‐immunotherapy. Plt‐M@P is prepared by using poly lactic‐co‐glycolic acid (PLGA)/PF3‐PPh3 complex as a nanocore, and then by co‐extrusion with platelet membranes. PF3‐PPh3 is an AIE‐active conjugated polyelectrolyte with photosensitizing capability for photodynamic therapy (PDT). Plt‐M@P exhibits superior tumor targeting capacity in vivo. When applied in small tumor‐bearing (~40 mm3) mice, Plt‐M@P‐mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm3), using Plt‐M@P‐mediated PDT or anti‐PD‐L1 alone is less effective, but the combination of both is effective in inhibiting tumor growth. Importantly, this combination therapy has good biocompatibility, as demonstrated by the absence of damage to the major organs, especially the reproductive system. In conclusion, we show that Plt‐M@P‐mediated PDT can improve anti‐PD‐L1 immunotherapy by enhancing antitumor effects, providing a promising strategy for the treatment of tumors with large burdens.

Abstract Photodynamic therapy (PDT) represents an attractive promising route for melanoma treatment. However, its therapeutic efficacy is compromised by inefficient drug delivery and high glutathione (GSH) levels in cancer cells. To overcome these challenges, microneedles (MNs) system loaded with GSH‐scavenging nanocomposites was presented for nitric oxide (NO) enhanced PDT. The nanocomposites consisted of S‐nitroso‐N‐acrylate penicillamine (SNAP; a NO donor) grafted fourth‐generation polyamide amine dendrimer (G4) and chlorin e6 (Ce6). Upon local insertion of polyvinylpyrrolidone MNs, G4‐SNAP/Ce6 composites were fast delivered and significantly amplified the therapeutic effects during PDT, via GSH depletion and reactive nitrogen species generation. Even with a single administration and low power light exposure, MNs with G4‐SNAP/Ce6 effectively halt the tumor progression. The system demonstrated better cancer ablation efficacy than Ce6 alone toward melanoma. The strategy may inspire new ideas for future PDT‐related therapy for skin tumors.

Abstract As the number of diabetics increases yearly and diabetic ulcer is the most concerned diabetic complication, it is of great urgency to develop a novel multifunctional material with high efficiency to promote diabetic wound healing. In this paper, ceria (CeO2)‐modified upconversion nanoparticles which loaded in polycaprolactone membranes were successfully prepared as a ceria‐based wound dressing for chronic wound healing. In this system, near‐infrared (NIR) light is used as a switch to control the photodynamic antibacterial therapy by converting the NIR photons into ultraviolet light, which can further trigger CeO2 to produce reactive oxygen species. In addition, the well‐known antioxidant ability of CeO2 endows the wound dressing with prominent capability to resist the oxidative stress around chronic wounds. In summary, both photodynamic antibacterial therapy and good antioxidant property are realized simultaneously in this CeO2‐based system to promote the healing of diabetic chronic wounds.

Abstract Immunotherapy, the most promising strategy of cancer treatment, has achieved promising outcomes, but its clinical efficacy in pancreatic cancer is limited mainly due to the complicated tumor immunosuppressive microenvironment. As a highly inflammatory form of immunogenic cell death (ICD), pyroptosis provides a great opportunity to alleviate immunosuppression and promote systemic immune responses in solid tumors. Herein, membrane‐targeted photosensitizer TBD‐3C with aggregation‐induced emission (AIE) feature to trigger pyroptosis‐aroused cancer immunotherapy via photodynamic therapy (PDT) is applied. The results reveal that pyroptotic cells induced by TBD‐3C could stimulate M1‐polarization of macrophages, cause maturation of dendritic cells (DCs), and activation of CD8+ cytotoxic T‐lymphocytes (CTLs). Pyroptosis‐aroused immunological responses could convert immunosuppressive “cold” tumor microenvironment (TME) to immunogenic “hot” TME, which not only inhibits primary pancreatic cancer growth but also attacks the distant tumor. This work establishes a platform with high biocompatibility for light‐controlled antitumor immunity and solid tumor immunotherapy aroused by cell pyroptosis.

Photodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third-generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface-modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT-induced hypoxia, disrupting the blood vascular networks in tumor tissues-vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. We propose that a synergistic outlook will help to address challenges such as deep-seated tumors, metastasis, or relapse and would lead to robust PDT response in patients., (© 2024 Wiley Periodicals LLC.)