Taeghwan Hyeon of the Institute for Basic Science (IBS) in Korea, Youngmee Jung of the Korea Institute of Science and Technology (KIST), and Byung-Soo Kim of Seoul National University, in collaboration with other researchers, recently devised a hybrid system involving ceria nanoparticles (Ce NPs) attached to mesenchymal stem cell nanovesicles to target the various pathogenic factors associated with rheumatoid arthritis (RA). This study demonstrates the efficacy of the therapy in treating and preventing RA through symptom relief and the induction of regulatory T (Treg) cells in a collagen-induced arthritis (CIA) mouse model. The findings were published in the prestigious journal, Nature Nanotechnology.1 RA is characterized by inflammatory autoimmune responses that lead to the loss of immune tolerance, synovial inflammation, and tissue damage, ultimately causing systemic and persistent functional limitations.2 The precise etiology of RA remains uncertain; however, it is established that the aforementioned factors can synergistically contribute to a self-perpetuating cycle that significantly influences the onset and progression of the disease. The standard initial approach to managing RA involves the administration of anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologics, albeit these pharmacological interventions primarily target symptom alleviation. While this method may provide short-term relief, it is crucial to acknowledge the potential adverse effects that may arise from prolonged drug use. As such, the optimal approach to treating RA should prioritize the restoration of normal immune function and the prompt suppression of inflammatory reactions and associated symptoms.3 Numerous studies have demonstrated the effective modulation of innate immunity through the promotion of anti-inflammatory M2 macrophages. Nevertheless, RA represents a chronic autoimmune condition that requires a more holistic strategy to restore immune function within both the innate and adaptive immune responses. Failing to achieve this objective necessitates the continued administration of palliative drugs, underscoring the critical need for a multifaceted intervention system capable of targeting numerous pathogenic factors to ensure comprehensive treatment of RA.4 The Ce–mesenchymal stem cell nanovesicle (MSCNV) system is engineered to capitalize on the antioxidant properties of Ce NPs to neutralize reactive oxygen species (ROS), a pivotal pathogenic factor in RA, and to induce a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. Simultaneously, MSCNVs within the hybrid system protect chondrocytes and deliver immunomodulatory cytokines, fostering a tolerogenic phenotype in dendritic cells (DCs) and the subsequent induction of Treg cells. This dual action targets the intricate interplay of pathogenic factors in RA, providing immediate relief and long-term disease modification. The development of the Ce–MSCNV hybrid system represents a paradigm shift in RA treatment by simultaneously targeting multiple pathogenic factors. RA, a disease affecting millions worldwide, is currently managed primarily through symptom-focused treatments. The Ce–MSCNV system exemplifies the potential of nanotechnology in immunomodulatory therapy. By conjugating Ce NPs with MSCNVs, the hybrid system synergizes the ROS-scavenging activity of Ce NPs to reduce inflammation and the immunomodulatory potential of MSCNVs to restore immune balance. This synergistic approach has been demonstrated to effectively treat and prevent RA in a CIA mouse model, presenting a promising alternative to conventional treatments (Figure 1). The Ce–MSCNVs' immunomodulatory effects are multifaceted. Ce NPs, with their inherent antioxidant capabilities, neutralize excess ROS, mitigating synovial inflammation. Meanwhile, MSCNVs protect chondrocytes and modulate the immune environment by inducing tolerogenic DCs, which in turn promote Treg cell differentiation. This rebalancing of the T-helper type 17 (TH17)/Treg cell ratio is essential for restoring immune tolerance in RA. The therapeutic efficacy of Ce–MSCNVs was evaluated in a CIA mouse model, where treatment led to significant improvements in clinical scores, reduced paw swelling and hyperthermia, and decreased hyperalgesia. Histological analysis revealed preservation of cartilage structure and diminished synovitis and angiogenesis in treated animals. Furthermore, the treatment facilitated a sustained restoration of the immune system, evidenced by the induction of Treg cells and the rebalance of TH17/Treg cell ratios. The Ce–MSCNV hybrid system represents a revolutionary advance in RA treatment, seamlessly combining anti-inflammatory and immunomodulatory functions. This research underscores the unmatched potential of nanotechnology in crafting multifunctional therapeutics capable of addressing the intricate and multifaceted pathogenesis of RA. The Ce–MSCNV system distinguishes itself by surpassing the constraints of conventional, single-modality treatments, offering instead a nuanced, multifactorial intervention strategy. Unlike traditional therapeutics that focus on symptom relief through individual drugs, the Ce–MSCNV system presents a holistic treatment protocol. It harmonizes the antioxidant prowess of CeNPs with the immunomodulatory capabilities of mesenchymal stem cell nanovesicles. This dual mechanism not only provides swift relief from inflammatory symptoms but also fosters a return to immune balance by recalibrating the T cell subset equilibrium, thereby supporting long-term immune system stability. However, alongside the therapeutic promise of the Ce–MSCNV system, there are pragmatic concerns that necessitate attention. Issues such as production costs, system stability, and scalability for clinical application must be rigorously examined. It is imperative for future studies to surmount these obstacles to affirm the Ce–MSCNV system as a practical and economically viable RA treatment option. This study accentuates the value of an approach that concurrently manages symptomatic relief and the root cause of immune misregulation, thereby paving the way for future exploration and clinical deployment in RA and a spectrum of autoimmune conditions. While the Ce–MSCNV system is replete with potential for transforming RA treatment, further investigation is essential to tackle questions of safety, efficacy, applicability, and fiscal sustainability, ensuring its successful translation from bench to bedside. Jing Zheng performed the study concept and design, Kai Zhou handled the development of the writing and review, and Xinlong He provided the revision of the paper. All authors read and approved the final paper. This work was supported by the Sichuan Science and Technology Department Key Research Projects (2019YFS0129). The authors declare no conflicts of interest. Not applicable. All data generated or analyzed during this study are included in this published article.

The clinical challenge of bone defects in the craniomaxillofacial region, which can lead to significant physiological dysfunction and psychological distress, persists due to the complex and unique anatomy of craniomaxillofacial bones. These critical-sized defects require the use of bone grafts or substitutes for effective reconstruction. However, current biomaterials and methods have specific limitations in meeting the clinical demands for structural reinforcement, mechanical support, exceptional biological performance, and aesthetically pleasing reconstruction of the facial structure. These drawbacks have led to a growing need for novel materials and technologies. The growing development of 3D printing can offer significant advantages to address these issues, as demonstrated by the fabrication of patient-specific bioactive constructs with controlled structural design for complex bone defects in medical applications using this technology. Poly (ether ether ketone) (PEEK), among a number of materials used, is gaining recognition as a feasible substitute for a customized structure that closely resembles natural bone. It has proven to be an excellent, conformable, and 3D-printable material with the potential to replace traditional autografts and titanium implants. However, its biological inertness poses certain limitations. Therefore, this review summarizes the distinctive features of craniomaxillofacial bones and current methods for bone reconstruction, and then focuses on the increasingly applied 3D printed PEEK constructs in this field and an update on the advanced modifications for improved mechanical properties, biological performance, and antibacterial capacity. Exploring the potential of 3D printed PEEK is expected to lead to more cost-effective, biocompatible, and personalized treatment of craniomaxillofacial bone defects in clinical applications.

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll-like receptor agonists delivery system CPG@Au NRs/m-R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m-R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m-R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor-associated macrophage polarization, triggering DCs maturation and inducing ICD.

Back Cover In article number 2201087, ZhiYong Qian and co-workers show that in the hybrid delivery systems CPG@Au NRs/m-R848, immunogenic cell death (ICD) induced by Au NRs could synergistically produce an in-situ vaccination effect with CPG ODN and R848. By triggering dendritic cells maturation and macrophage reprogramming, this photothermal immunotherapy strategy holds great potential in generating systemic and lasting antitumor immunity by inhibiting tumor growth and metastases simultaneously.

Osteoarthritis (OA) is a common joint condition that is a leading cause of disability worldwide. There are currently no disease-modifying treatments for osteoarthritis, which is associated with multiple kinds of inflammatory cytokines produced by M1 macrophages in the synovium of the joint. Despite recent therapeutic advancements with anti-cytokine biologics, the OA therapy response rate continues to be inadequate. To treat OA, the pro-inflammatory and anti-inflammatory responses of synoviocytes and macrophages must be controlled simultaneously. Therefore, the immune regulation capabilities of an ideal nano-drug should not only minimize pro-inflammatory responses but also effectively boost anti-inflammatory responses. In this paper, an M2H@RPK nanotherapeutic system was developed, KAFAK and shRNA-LEPR were condensed with polyethylenimine (PEI) to form a complex, which was then modified with hyaluronic acid (HA) to negatively charge to cover the M2 membrane. It was discovered that the repolarization of macrophages from the M1 to the M2 phenotype lowered pro-inflammatory responses while enhancing anti-inflammatory responses in macrophages and synoviocytes. In vitro and in vivo studies demonstrate that M2H@RPK dramatically decreases proinflammatory cytokines, controls synovial inflammation, and provides significant therapeutic efficacy by reducing joint damage. Overall, it has been demonstrated that M2H@RPK provides inflammation-targeted therapy by macrophage repolarization, and it represents a promising OA therapeutic strategy.

Bladder cancer is one of the most common malignant tumors in the urinary system worldwide. The poor permeability and uncontrollable release of drug and hypoxia of tumor tissues were the main reasons leading to poor therapeutic effect of chemo-photodynamic therapy for bladder cancer. To solve the above problems, a tumor-targeting peptide Arg-Gly-Asp (RGD) modified platinum nanozyme (PtNP) co-loaded glutathione (GSH)-responsive prodrug nanoparticles (PTX-SS-HPPH/Pt@RGD-NP) was constructed. Firstly, a GSH-responsive prodrug (PTX-SS-HPPH) was prepared by introducing a disulfide bond between paclitaxel (PTX) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), which could realize the GSH-responsive release of the drug at the tumor sites. Also, the distearoylphosphoethanolamine-poly (ethylene glycol)-RGD peptide (DSPE-PEG-RGD) modified the prodrug to enhance the targeting and permeability ability to bladder cancer cells. Besides, to alleviate the hypoxia of tumor tissues, PtNP was introduced to produce oxygen (O2) and improve photodynamic therapy efficiency. The results showed that the PTX-SS-HPPH/Pt@RGD-NP could achieve GSH-responsive drug release in tumor microenvironment, enhance the drug accumulation time and permeability at tumor sites in T24 subcutaneous tumor model and T24 orthotopic bladder tumor model, and alleviate hypoxia in tumor tissues, thus realizing enhanced chemo-photodynamic therapy for bladder cancer, and providing new strategies and methods for clinical treatment of bladder cancer.

Improving the efficacy of melanoma treatment remains an important global challenge. Here, we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2) based immunotherapy in an effort to address this challenge. Short-hairpin RNA (shRNA) targeting Ptpn2 was coencapsulated with doxorubicin (DOX) in the cell membrane of M1 macrophages (M1HD@RPR). The prepared nanoparticles (NPs) were effectively phagocytosed by B16F10 cells and M1 macrophages, but not by M0 macrophages. Hence, NP evasion from the reticuloendothelial system (RES) was improved and NP enrichment in tumor sites increased. M1HD@RPR can directly kill tumor cells and stimulate immunogenic cell death (ICD) by DOX and downregulate Ptpn2. It can promote M1 macrophage polarization and dendritic cell maturation and increase the proportion of CD8+ T cells. M1HD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor cells without harming the surrounding tissue. These findings establish M1HD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reductionresponsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targe ting peptide cyclo(Asp-D-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy. 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Tumor photothermal therapy (PTT) has spatiotemporal controllability, is minimally invasive, has high selectivity for local cancers, and has a good anti-cancer effect; thus, it has been confirmed as a promising cancer treatment. However, regional high temperatures during treatment may damage normal tissues and even induce inflammation and tumor metastasis. In this study, a multifunctional cascade nanoreactor based on hollow mesoporous silica (HMSN) was prepared by loading a photothermal agent (PTA) prodrug of 3,3′,5,5′-tetramethylbenzidine (TMB), glucose oxidase (Gox), and horseradish peroxidase (HRP), which are used for the synergistic cancer therapy of starvation therapy (ST) and PTT. First, the adenosine triphosphate(ATP) generation of tumor cells was obstructed using Gox-mediated starvation therapy, and the heat shock protein-70 (HSP-70) level was further used to reduce the thermo-resistance. Then, HRP improved the hypoxic state of the tumor microenvironment (TME) by consuming H2O2 and further oxidizing the colorless TMB(PTA prodrug) into OXTMB (PTA) with an excellent photothermal effect. In addition,the glutathione(GSH) level of the tumor cells was also downregulated, which further promoted the process of apoptosis. Ultimately, both the in-vivo and in-vitro studies showed that the nanoreactor significantly inhibited the growth of tumor cells and ablated the solid tumor, which provides another possibility for clinical intervention.

[This corrects the article DOI: 10.1016/j.bioactmat.2020.04.002.].

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble Ag2S nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that Ag2S NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the Ag2S NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.

Minimizing drug leakage in systemic circulation, synchronizing the in vivo fate of multiple drugs, and precisely controlling tumor locoregional drug release, remain challenging for nanomedicine‐based cancer therapy. Here, a reactive oxygen species (ROS)‐responsive camptothecin (CPT) prodrug delivery system (MPEG‐(TK‐CPT)‐PPa) is developed, in which CPT and photosensitizer pyropheophorbide‐a (PPa) are concurrently conjugated to the same poly(ethylene glycol) methyl ether (MPEG) via ROS‐responsive thioketal (TK) and lipid linkage. The synthesized MPEG‐(TK‐CPT)‐PPa conjugate self‐assembles to form nanoparticles (NPs) (43.6 ± 0.8 nm) in solution. The covalently conjugated prodrug prevents drug leakage during systemic circulation and synchronizes the in vivo distribution of the two drugs. The generated fluorescence signal of PPa helps precisely track and locate the NPs at tumor sites. Under the guidance of imaging, a near‐infrared laser locally irradiates tumor tissue upon reaching the strongest fluorescence. The ROS generated by PPa not only cleaves the TK linkage and then triggers locoregional, controllable and on‐demand CPT release, but also exhibits cytotoxic effects on tumor cells. Thus, CPT‐mediated chemotherapy and PPa‐induced photodynamic therapy lead to the combined and enhanced suppression of tumor growth. Accordingly, such laser‐triggered, localized, controllable, and on‐demand drug release systems may provide an alternative option for CPT formulations.

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function. In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of ~85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.

The prevalence of skin cancer is rising along with the rapid population aging in recent years. Traditional therapies, such as surgical treatment, radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, may accompany serious side effects, limiting their clinical benefits. According to the biological characteristics of skin cancer, we have already established two kinds of synergetic systems of photothermal therapy (microneedle) and chemotherapy, containing gold nanorods (GNR). Although the microneedle system exhibited great potential for skin cancer treatment, the system could be still improved further. So, we designed a near-infrared light-responsive 5-fluorouracil (5-Fu) and indocyanine green (ICG) loaded monomethoxy-poly (ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticle (5-Fu-ICG-MPEG-PCL), and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system (HA MN) to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers, including human epidermoid cancer and melanoma. In this system, hyaluronic acid, the microneedle carrier, possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant; 5-Fu is recommended by FDA for skin cancer treatment; ICG, a photothermal agent, possesses a strong photothermal ability and is approved by FDA for its use in the human body. We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin, and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer, improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.

Systemic administration of anticancer therapeutic agents remains a crucial strategy for clinical cancer therapy. However, poor drug accumulation at tumor sites and severe side effects to normal tissues induced by off-target effects lower their therapeutic efficiency and limit their deep application in clinical settings. How to overcome these issues has continuously raised concerns. Reportedly, injectable thermosensitive hydrogels are good carriers for local drug delivery systems, demonstrating a flowable and injectable sol state at room temperature, easily loading therapeutic agents with large loading contents. Under normal body temperature, these hydrogels are stimulated to undergo a phase transition to an immobile gel state, which serves as a drug reservoir at local injection sites. After intratumoral or peritumoral injection, the localized hydrogel reservoir shows a slow and sustained drug release behavior, and can also targeted deliver therapeutic agents to cancer cells instead of normal cells, improving the therapeutic efficiency and reducing systemic side effects. This review summarizes the development of injectable thermosensitive hydrogel systems, reviews the research application advances of these systems in different therapy strategies for cancer, discusses the present issues and awaits their future in clinical applications.

Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non-small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test-tube-inversion method shows that this ERT-loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non-flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano-scaled delivery system for localized anticancer therapies.

The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.