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Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT., (© 2024. The Author(s).)

Disulfiram (DSF), a U.S. Food and Drug Administration (FDA)-approved drug for the treatment of chronic alcoholism, is also used as an antitumor drug in combination with Cu 2+ ions. However, studies have shown that the endogenous Cu 2+ dose in tumor tissues is still insufficient to form relatively high levels of a bis( N , N- diethyldithiocarbamate) copper(II) complex (denoted as Cu(DTC) 2 ) to selectively eradicate cancer cells. Here, DSF-loaded hollow copper sulfide nanoparticles (DSF@PEG-HCuSNPs) were designed to achieve tumor microenvironment (TME)-activated in situ formation of cytotoxic Cu(DTC) 2 for NIR-II-induced, photonic hyperthermia-enhanced, and DSF-initiated cancer chemotherapy. The acidic TME triggered the gradual degradation of DSF@PEG-HCuSNPs, promoting the rapid release of DSF and Cu 2+ ions, causing the in situ formation of cytotoxic Cu(DTC) 2 , to achieve efficient DSF-based chemotherapy. Additionally, DSF@PEG-HCuSNPs exhibited a notably high photothermal conversion efficiency of 23.8% at the second near-infrared (NIR-II) biowindow, thus significantly inducing photonic hyperthermia to eliminate cancer cells. Both in vitro and in vivo studies confirmed the effective photonic hyperthermia-induced chemotherapeutic efficacy of DSF by integrating the in situ formation of toxic Cu(DTC) 2 complexes and evident temperature elevation upon NIR-II laser irradiation. Thus, this study represents a distinctive paradigm of in situ Cu 2+ chelation-initiated "nontoxicity-to-toxicity" transformation for photonic hyperthermia-augmented DSF-based cancer chemotherapy.

Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) induced by an imbalance of oxidants and antioxidants is an important aspect in anticancer therapy, however, as an adaptive response, excessive glutathione (GSH) in the tumor microenvironment (TME) acts as an antioxidant against high reactive oxygen species (ROS) levels and prevents OS damage to maintain redox homoeostasis, suppressing the clinical efficacy of OS-induced anticancer therapies. Results: A naturally occurring ROS-activating drug, galangin (GAL), is introduced into a Fenton-like catalyst (SiO2@MnO2) to form a TME stimulus-responsive hybrid nanopharmaceutical (SiO2-GAL@MnO2, denoted SG@M) for enhancing oxidative stress. Once exposed to TME, as MnO2 responds and consumes GSH, the released Mn2+ converts endogenous hydrogen peroxide (H2O2) into hydroxyl radicals (·OH), which together with the subsequent release of GAL from SiO2 increases ROS. The "overwhelming" ROS cause OS-mediated mitochondrial malfunction with a decrease in mitochondrial membrane potential (MMP), which releases cytochrome c from mitochondria, activates the Caspase 9/Caspase 3 apoptotic cascade pathway. Downregulation of JAK2 and STAT3 phosphorylation levels blocks the JAK2/STAT3 cell proliferation pathway, whereas downregulation of Cyclin B1 protein levels arrest the cell cycle in the G2/M phase. During 18 days of in vivo treatment observation, tumor growth inhibition was found to be 62.7%, inhibiting the progression of pancreatic cancer. Additionally, the O2 and Mn2+ released during this cascade catalytic effect improve ultrasound imaging (USI) and magnetic resonance imaging (MRI), respectively. Conclusion: This hybrid nanopharmaceutical based on oxidative stress amplification provides a strategy for multifunctional integrated therapy of malignant tumors and image-visualized pharmaceutical delivery. [ABSTRACT FROM AUTHOR]

Proteolysis targeting chimeras (PROTACs) technology is an emerging approach to degrade disease‐associated proteins. Here, we report carbon‐dot (CD)‐based PROTACs (CDTACs) that degrade membrane proteins via the ubiquitin‐proteasome system. CDTACs can bind to programmed cell death ligand 1 (PD‐L1), recruit cereblon (CRBN) to induce PD‐L1 ubiquitination, and degrade them with proteasomes. Fasting‐mimicking diet (FMD) is also used to enhance the cellular uptake and proteasome activity. More than 99 % or 90 % of PD‐L1 in CT26 or B16‐F10 tumor cells can be degraded by CDTACs, respectively. Furthermore, CDTACs can activate the stimulator of interferon genes (STING) pathway to trigger immune responses. Thus, CDTACs with FMD treatment effectively inhibit the growth of CT26 and B16‐F10 tumors. Compared with small‐molecule‐based PROTACs, CDTACs offer several advantages, such as efficient membrane protein degradation, targeted tumor accumulation, immune system activation, and in vivo detection. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly malignant, fatal disease with a complex tumor microenvironment (TME) characterized by severe immunosuppression and malformed vascular structures, thus most advanced HCC patients do not respond well to current mainstream pharmacotherapy and T-cell-related immunotherapy. Therefore, an efficient immunovascular crosstalk modulation strategy may help combat HCC by reversing immunosuppression and vessel normalization, especially by reprogramming tumor associated macrophages (TAMs). In this study, tyrosine kinase inhibitor lenvatinib (Len) was loaded into mesoporous Fe 3 O 4 (mFe) nanoparticles (NPs), and bovine serum albumin (BSA) was attached to the NP surface to produce a metallodrug (BSA-mFe@Len NPs). In acidic TME, BSA allowed pH-responsive Len release and mFe exposure. Len directly triggered HCC apoptosis and changed the abnormal TME via vessel normalization, cytotoxic T-lymphocyte recruitment, and regulatory T-cell elimination at tailored dosages. After TAM phagocytosis, mFe NPs reprogrammed TAMs into M1 phenotypes to synergistically amplify antitumor immunity. The metallodrug achieved significant tumor growth inhibition, induced tumor vessel normalization effects, and acquired instant antitumor immunity as well as long-term immune memory in vivo. Furthermore, it displayed good T 2 weighted magnetic resonance imaging performance, indicating potential theranostic applications. Collectively, this research provides new insights for unleashing the multifaceted potential of current pharmaceuticals in synergy with metallic nanomedicine for treating intractable liver cancer. Current pharmacotherapy and immunotherapy have limited success in treating advanced hepatocellular carcinoma (HCC) due to its complex tumor microenvironment (TME). Hence, this work first put forward a theranostic metallodrug by loading lenvatinib (Len) into mesoporous Fe 3 O 4 (mFe) nanoparticles (NPs) and coating a pH-degradable bovine serum albumin corona onto the surface. The metallodrug was able to modulate immunovascular TME for combating HCC via metalloimmunotherapy induced by the mFe NPs and Len's multiple functions (direct triggering of tumor apoptosis, vessel normalization, cytotoxic T-lymphocyte recruitment, and regulatory T-cell elimination). In vivo experiments showed that the metallodrug could significantly inhibit HCC growth and evoke long-term antitumor immune memory, paving a new avenue for treating advanced HCC patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Effective accumulation of nanoparticles (NPs) in tumor regions is one of the major motivations in nanotechnology research and that the establishment of an efficient targeting nanoplatform for the treatment of malignant tumors is urgently needed for theranostic applications. In this study, we engineered multifunctional sequential targeting NPs for achieving synergistic antiangiogenic photothermal therapy (PTT) and multimodal imaging-guided diagnosis for anaplastic thyroid carcinoma (ATC) theranostics. Antibody bevacizumab with an affinity towards vascular endothelial growth factor (VEGF) on the tumor cell surface was conjugated onto the surface of polymer NPs for VEGF targeting and antiangiogenic therapy. Encapsulated IR825 was employed as a photothermal agent (PTA) with a mitochondrial targeting capability, which further cascades NPs into mitochondria to enhance hyperthermic efficiency in the ablation of tumor cells. Importantly, the combination of bevacizumab and IR825 in a single nanosystem achieved desirable accumulations of NPs and that sequential targeted PTT combined with antiangiogenesis significantly promoted the therapeutic efficiency in eradicating tumors by near-infrared (NIR) laser irradiation. Furthermore, these NPs are extraordinary contrast agents for photoacoustic, ultrasound and fluorescence imaging applications, providing multimodal imaging capabilities for therapeutic monitoring and a precise diagnosis. Therefore, this multifunctional nanoplatform provides a promising theranostic strategy for extremely malignant ATC. Anaplastic thyroid carcinoma (ATC), with extremely aggressive behavior, lacks a satisfactory therapeutic method and a comprehensive early diagnostic strategy. Herein, we successfully synthesized a sequential targeting nanoplatform (IR825@Bev-PLGA-PFP NPs) with theranostic function, which specifically binds to VEGF on the tumor cell surface and further cascades into mitochondria to achieve effective accumulation of NPs in the tumor regions. As a result, it solves the urgent demand for ATC detection and therapy. By breaking the limitation of traditional target, such as low efficacy and frequent recurrence as the results of low accumulation, sequential targeting combined with synergistic antiangiogenic PTT completely eradicates tumors without any residual tissue and side effect. Therefore, this strategy paves a solid way for further investigation in the theranostic progressing of ATC. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract: Phototherapy has emerged as a novel therapeutic modality for cancer treatment, but its low therapeutic efficacy severely hinders further extensive clinical translation and application. This study reports amplifying the phototherapeutic efficacy by constructing a near‐infrared (NIR)‐responsive multifunctional nanoplatform for synergistic cancer phototherapy by a single NIR irradiation, which can concurrently achieve mitochondria‐targeting phototherapy, synergistic photothermal therapy (PTT)/photodynamic therapy (PDT), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring. Perfluorooctyl bromide based nanoliposomes are constructed for oxygen delivery into tumors, performing the functions of red blood cells (RBCs) for oxygen delivery (“Nano‐RBC” nanosystem), which can alleviate the tumor hypoxia and enhance the PDT efficacy. The mitochondria‐targeting performance for enhanced and synergistic PDT/PTT is demonstrated as assisted by nanoliposomes. In particular, these “Nano‐RBCs” can also act as the contrast agents for concurrent computed tomography, photoacoustic, and fluorescence multiple imaging, providing the potential imaging capability for phototherapeutic guidance and monitoring. This provides a novel strategy to achieve high therapeutic efficacy of phototherapy by the rational design of multifunctional nanoplatforms with the unique performances of mitochondria targeting, synergistic PDT/PTT by a single NIR irradiation (808 nm), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring. [ABSTRACT FROM AUTHOR]

Abstract: The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the leading cause of mortality globally. RBC–platelet hybrid membrane-coated nanoparticles ([RBC-P]NPs), which biologically mimic platelets in vivo , display evidence of anti-atherosclerotic activity. The efficacy of a targeted RBC–platelet hybrid membrane-coated nanoparticles ([RBC-P]NP)-based approach was investigated as a primary preventive measure against atherosclerosis. A ligand-receptor interactome analysis conducted with circulating platelets and monocytes derived from CAD patients and healthy controls identified CXCL8-CXCR2 as a key platelet ligand-monocyte receptor dyad in CAD patients. Based on this analysis, a novel anti-CXCR2 [RBC-P]NP that specifically binds to CXCR2 and blocks the interaction between CXCL8 and CXCR2 was engineered and characterized. Administering anti-CXCR2 [RBC-P]NPs to Western diet-fed Ldlr −/− mice led to diminished plaque size, necrosis, and intraplaque macrophage accumulation relative to control [RBC-P]NPs or vehicle. Importantly, anti-CXCR2 [RBC-P]NPs demonstrated no adverse bleeding/hemorrhagic effects. A series of in vitro experiments was conducted to characterize anti-CXCR2 [RBC-P]NP's mechanism of action in plaque macrophages. Mechanistically, anti-CXCR2 [RBC-P]NPs inhibited p38α (Mapk14)-mediated, pro-inflammatory M1 skewing and corrected efferocytosis in plaque macrophages. This targeted [RBC-P]NP-based approach, in which the cardioprotective effects of anti-CXCR2 [RBC-P]NP therapy overweighs its bleeding/hemorrhagic risks, could potentially be used to proactively manage atherosclerotic progression in at-risk populations. [Display omitted] • CXCL8-CXCR2 is a key platelet ligand-monocyte receptor dyad in CAD patients. • An anti-CXCR2 [RBC-P]NP that blocks the CXCL8-CXCR2 interaction was engineered. • Anti-CXCR2 [RBC-P]NPs reduced atherogenesis in Western diet-fed Ldlr −/− mice. • Anti-CXCR2 [RBC-P]NPs demonstrated no adverse bleeding/hemorrhagic effects. • Anti-CXCR2 [RBC-P]NPs inhibited p38α-mediated, pro-inflammatory M1 skewing. [ABSTRACT FROM AUTHOR]

• Conceptual advance: comprehensive thrombolytic management. • Design advance: the first time uses two FDA-approved drugs. • Models advance: the carotid thrombosis model and black-tail model. • Treatment advance: targeted enhanced fibrinolysis and ROS scavenging. • Extensive common interests: high clinical translation potential. Thrombotic diseases cause significant risks of disability and death worldwide. However, conventional thrombolytic drugs have short half-lives, poor targeting capabilities, limited therapeutic effects， and narrow therapeutic windows. Moreover, most basic studies focus only on thrombolytic efficiency and ignore the inflammatory factors that promote thrombosis progression, such as reactive oxygen species (ROS)-mediated oxidative stress. Therefore, to achieve comprehensive and effective thrombolytic management, both targeted thrombolytic therapy and the elimination of inflammatory factors must be achieved. In this study, we developed a platelet membrane (PM)-functionalized hollow mesoporous Prussian blue nanomedicine (HMPB-rtPA@PM), which was innovatively coassembled from two FDA-approved drugs (Prussian blue (PB) and alteplase (rtPA)) and showed marked advantages in both thrombi targeting and photothermal/pharmacological synergistic fibrinolysis. Moreover, HMPB-rtPA@PM exhibited the potential to inhibit platelet aggregation and regulate the inflammatory microenvironment by scavenging ROS. As expected, this nanomedicine not only achieved more efficient thrombolysis in both thrombus models but also delayed thrombosis progression through therapeutic visualization in the black tail model. Such rational therapeutic principle provides a broad platform for the comprehensive management of thrombotic diseases. [ABSTRACT FROM AUTHOR]

As a highly biocompatible NIR dye, indocyanine green (ICG) has been widely explored for cancer treatment due to its various energy level transition pathways upon NIR light excitation simultaneously, which leads to different theranostic effects ( eg. Photoacoustic (PA) and fluorescence imaging (FL), photodynamic and photothermal therapy (PDT&PTT)). However, the theranostic efficiency of ICG is restricted intrinsically, owing to the competitive relationship of its co-existing imaging and therapeutic effect. Moreover, the extrinsic hypoxia nature of tumor further limits its therapeutic effect, especially for the oxygen-dependent PDT. Herein, perfluorooctyl bromide (PFOB), another biocompatible chemical, was integrated with ICG in a nanoliposome structure via a facile two-step emulsion method. Such an ICG&PFOB co-loaded nanoliposomes (LIP-PFOB-ICG) realized computed tomography (CT) contrast imaging in vivo , providing better anatomical information of tumor in comparison to ICG enabled PA and FL imaging. More importantly, LIP-PFOB-ICG inhibited MDA-MB-231 tumor growth completely via intravenous injection through enhanced PDT&PTT synergistic therapy due to the excellent oxygen carrying ability of PFOB, which effectively attenuated tumor hypoxia, improved the efficiency of collisional energy transfer between ICG and oxygen and reduced the expression of heat shock protein (HSP). As expected, the introduction of PFOB within nanoliposomes with ICG has augmented the theranostic effect of ICG comprehensively, which makes this simple biocompatible liposome-based nanoagent a potential candidate for clinical imaging guided phototherapy of cancer. [ABSTRACT FROM AUTHOR]

The fast development of nanotechnology has provided a new efficient strategy for enhancing the therapeutic efficiency of various treatment modalities against cancer. However, the improvement of minimally invasive microwave therapy based on nanomaterials has not been realized. In this work, we successfully designed and synthesized a novel folate-targeted nanodroplet (TPN) with a composite mixture of perfluorocarbons as the core and lipid as the shell, which exerts the distinctive dual functions as the adjuvant for highly efficient percutaneous ultrasound imaging-guided microwave ablation (MWA) of tumors. Based on the unique phase-changeable performance of TPN nanosystem, a novel microwave-droplet vaporization (MWDV) strategy was proposed, for the first time, to overcome the critical issues of traditional acoustic-droplet vaporization (ADV) and optical-droplet vaporization (ODV) for cancer theranostics. Especially, the elaborately designed TPN can overcome the challenges of indistinct imaging of ablation margin and the limited ablation zone of MWA modality against cancer. The high efficiency of this new MWDV strategy has been systematically elucidated in vitro, ex vivo and in vivo . Therefore, such a successful demonstration of the role of nanomaterials (TPN in this case) in ultrasound imaging-guided MWA therapy against cancer provides a highly feasible strategy to effectively enhance the MWA outcome with the specific features of high efficiency and biosafety. [ABSTRACT FROM AUTHOR]

Insufficient concentrations of intracellular substrates such as hypoxia and H 2 O 2 considerably reduce the effectiveness of reactive oxygen species (ROS)-associated cancer therapy. Modulating the tumor microenvironment (TME) for augmenting efficacy has become a promising strategy. Herein, a phase-change cascaded nanomedicine (Lap-IrO x @PCM) was constructed via co-encapsulation of iridium oxide nanozyme (IrO x) and β-lapachone (Lap) by using thermal-responsive phase-change materials (PCMs). After photothermal activation, the protective PCM layer was melted, causing the rapid release of IrO x and Lap. Simultaneously, the peroxidase-like nanozyme IrO x reacted with endogenous H 2 O 2 to liberate highly toxic hydroxyl radicals (•OH) for inducing tumor cell death. Meanwhile, IrO x as another glutathione peroxidase nanozyme also consumed glutathione (GSH) to protect ROS from scavenging. Importantly, the released Lap efficiently generated H 2 O 2 for facilitating the catalytic efficacy of IrO x and provoke the cleavage of heat shock protein 90 (Hsp90) for overcoming tumor heat tolerance in photothermal therapy (PTT). As systematically demonstrated both in vitro and in vivo , this well-defined system achieved a superior antitumor effect via mild photothermal-enhanced nanocatalytic therapy. Our findings have provided the proof of concept of the phase change-mediated, in vivo catalytic activity of nanozymes that can be customized for intensive, TME-mediated, self-enhanced nanocatalytic cancer therapy. We report a domino-like nanomedicine (Lap-IrO x @PCM) that possesses both H 2 O 2 self-supply and GSH-elimination properties for achieving highly cascaded catalytic-therapeutic outcomes by integrating a peroxidase-like moiety of the IrO x nanozyme and β-Lapachone within a thermal-responsive phase-change material (PCM). This work presents a universal idea of a phase-change nanomedicine design for intensive, mild PTT-enhanced nanocatalytic therapy. [Display omitted] • A concept of "phase change nanomedicine-mediated H 2 O 2 self-supplying" strategy is proposed. • β-Lapachone is exploited as a H 2 O 2 productor and heat shock protein inhibitor to fabricate cascade nanocatalyst. • The engineered Lap-IrO x @PCM presents an idea of a phase-change nanomedicine design for intensive nanocatalytic therapy. • This work provides the first example of a nanozyme-type phase-change nanomedicine. [ABSTRACT FROM AUTHOR]

Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as "thermoferroptosis sensitization". Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable. [ABSTRACT FROM AUTHOR]