Theranostic Nanoplatform Research Articles

Stimulus-Detonated Biomimetic "Nanobomb" with Controlled Release of HSP90 Inhibitor to Disrupt Mitochondrial Function for Synergistic Gas and Photothermal Therapy.

Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H2 O2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn2+ enables T1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.

Acid-responsive DNA-Au nanomachine with active/passive dual-targeting capacity for combinational cancer therapy

DNA nanotechnology has attracted intense interest in biomedicine due to the advantages of good biocompatibility, structural programmability and multifunctionality. Herein, a DNA-Au nanomachine with active/passive dual-targeting capacity has been constructed, achieving lysosomal acidic microenvironment-activated combinational chemo-photothermal therapy of cervical carcinoma. The three-dimensional DNA nanoflowers (DNFs) are readily prepared via rolling circle amplification (RCA), in which the active targeting units (C-9S aptamers) for HeLa cells and drug-loading sites for doxorubicin (Dox) are rationally designed in the circular template. Meanwhile, the bovine serum albumin (BSA)-modified gold nanoparticles (BSA-AuNPs) with pH-responsive charge reversal ability are internalized into cancer cells through passive targeting mechanism of enhanced permeability and retention (EPR) effect. Under acidic stimuli (endosome and lysosome), the loaded Dox in DNFs is controllably released for targeted chemotherapy, and the charge of BSA-AuNPs is reversed from negative to positive in lysosome, resulting in the aggregation of BSA-AuNPs on DNFs through electrostatic interaction. Thus, hyperthermia is produced upon 808 nm laser irradiation for photothermal therapy (PTT). The in vitro and in vivo results demonstrate the highly chemo-photothermal therapy effect on cervical cancer based on the proposed DNA-Au nanomachine, providing a powerful and potential nanotheranostic platform for targeted combinational therapy of cancers in clinical applications.

Biomimetic Gold Nanorods Modified with Erythrocyte Membranes for Imaging-Guided Photothermal/Gene Synergistic Therapy.

Pancreatic cancer (PC) is one of the most malignant cancers that develops rapidly and carries a poor prognosis. Synergistic cancer therapy strategy could enhance the clinical efficacy compared to either treatment alone. In this study, gold nanorods (AuNRs) were used as siRNA delivery vehicles to interfere with the oncogenes of KRAS. In addition, AuNRs were one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser and achieve rapid photothermal therapy for malignant cancer cells. Modification of the erythrocyte membrane and antibody Plectin-1 occurred on the surface of the AuNRs, making them a promising target nanocarrier for enhancing antitumor effects. As a result, biomimetic nanoprobes presented advantages in biocompatibility, targeting capability, and drug-loading efficiency. Moreover, excellent antitumor effects have been achieved by synergistic photothermal/gene treatment. Therefore, our study would provide a general strategy to construct a multifunctional biomimetic theranostic multifunctional nanoplatform for preclinical studies of PC.

Direct Synthesis of Aliphatic Polyesters with Pendant Hydroxyl Groups from Bio-Renewable Monomers: A Reactive Precursor for Functionalized Biomaterials.

Introducing desired functionalities into biomaterials is an effective way to obtain functionalized biomaterials. A versatile platform with the possibility of postsynthesis functionalization is highly desired but challenging in biomedical engineering. In this work, linear aliphatic polyesters with pendant hydroxyl (PEOH) groups were directly synthesized using renewable malic acid/tartaric acid as raw materials under mild conditions through the polyesterification reaction promoted by 1,1,3,3-tetramethylguanidine (TMG). The hydroxyl groups on PEOH provide an active stepping stone for the fabrication of demanded functionalized polyesters. We demonstrated the possibility of the PEOH as a reactive precursor for functional group transformation, coupling of bioactive molecules, and formation of crosslinking networks. Moreover, a theranostic nanoplatform (mPEG-b-(P7-asp&TPV)-b-mPEG NPs) was synthesized using PEOH as a reactive stepping stone by the programmable combination of the above functionalization methods. Overall, these hydroxyl-containing polyesters have great potential in biological applications.

An NIR-II light-responsive nanoplatform for photothermal and enhanced photodynamic synergistic therapy toward drug-resistant bacterial infection and hypoxia relief in subcutaneous wound healing

The drug-resistant bacterial infection has seriously threatened human health and thus it is urgent to develop new and effective drugs to overcome the antibiotic resistance crisis. Herein, a near-infrared-II (NIR-II) region light-responsive Pd rough nanoshells on metal-organic framework (MOF) of UiO-66-NH2 (UiO-66-NH2@Pdshell) has been developed for the first time, which was further loaded with the photosensitizer IR780 to ultimately yield UiO-66-NH2@Pdshell-IR780 (UPI) as the core-shell theranostic nanoplatform. The Pd rough nanoshells demonstrate promising photothermal conversion efficiency, superoxide dismutase (SOD)-like activity, and light-enhanced catalase (CAT)-like activity. In the non-healing wound inflammatory microenvironment with overexpression of reactive oxygen species (ROS) caused by subcutaneous bacterial infection, Pd rough nanoshells in UPI transforms ROS, such as O2•−, into H2O2 and efficiently catalyzes the decomposition of the formed and endogenous H2O2 to produce O2. The O2 production process could be enhanced by NIR-II light to facilitate photodynamic efficacy of IR780 to prime rapid clearance of methicillin-resistant Staphylococcus aureus (MRSA) through biofilm inhibition, along with down-regulation of hypoxia inducible factor-1α (HIF-1α) and relief of inflammation, thus promote wound healing. Moreover, UPI exhibits negligible biotoxicity in vitro and in vivo. This work provides a method for preparing promising Pd-based nanomaterials toward subcutaneous infection treatment and wound healing.

X‐Ray‐triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization

AbstractCarbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X‐ray‐triggered carbon monoxide (CO) and manganese dioxide (MnO2) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV‐responsive Mn2(CO)10 is not only indirectly activated to release CO by X‐ray but can also be degraded into MnO2. A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2, as the photolytic byproduct of Mn2(CO)10, has both glutathione (GSH) depletion and Fenton‐like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X‐ray‐activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X‐ray‐activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.

X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization.

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO2 ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn2 (CO)10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO2 . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2 , as the photolytic byproduct of Mn2 (CO)10 , has both glutathione (GSH) depletion and Fenton-like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.

Intelligent Pd1.7Bi@CeO2 Nanosystem with Dual-Enzyme-Mimetic Activities for Cancer Hypoxia Relief and Synergistic Photothermal/Photodynamic/Chemodynamic Therapy.

Reactive oxygen species-mediated therapeutic strategies, including chemodynamic therapy (CDT) and photodynamic therapy (PDT), have exhibited translational promise for effective cancer management. However, monotherapy often ends up with the incomplete elimination of the entire tumor due to inherent limitations. Herein, we report a core-shell-structured Pd1.7Bi@CeO2-ICG (PBCI) nanoplatform constructed by a facile and effective strategy for synergistic CDT, PDT, and photothermal therapy. In the system, both Pd1.7Bi and CeO2 constituents exhibit peroxidase- and catalase-like characteristics, which not only generate cytotoxic hydroxyl radicals (•OH) for CDT but also produce O2 in situ and relieve tumor hypoxia for enhanced PDT. Furthermore, upon 808 nm laser irradiation, Pd1.7Bi@CeO2 and indocyanine green (ICG) coordinately prompt favorable photothermia, resulting in thermodynamically amplified catalytic activities. Meanwhile, PBCI is a contrast agent for near-infrared fluorescence imaging to determine the optimal laser therapeutic window in vivo. Consequently, effective tumor elimination was realized through the above-combined functions. The as-synthesized unitary PBCI theranostic nanoplatform represents a potential one-size-fits-all approach in multimodal synergistic therapy of hypoxic tumors.

Assembling AgAuSe Quantum Dots with Peptidoglycan and Neutrophils to Realize Enhanced Tumor Targeting, NIR (II) Imaging, and Sonodynamic Therapy.

Significant progress is made in drug delivery systems, but they still face problems such as poor stability in vivo, off-target drugs, and difficulty in crossing biological barriers. It is urgent to realize efficient targeted delivery and precisely controlled sustained release of drugs by using the integrated nanoplatform. Theranostic nanoplatform is a new biomedical technology that combines diagnosis or monitoring of diseases with treatment. Here, an integrated strategy of diagnosis and treatment is reported for delivering NIR-II imaged and therapeutic AgAuSe quantum dots (QDs) carried by peptidoglycan multilayer networks of bacteria to hitchhike circulating neutrophils for targeting the tumor. The assembled nanomaterials have good stability, which can not only initiate endogenous cells for drug delivery and achieve efficient targeting, but also guide drug imaging with excellent fluorescence property. Meanwhile, the elimination of established solid tumor is achieved with the administration of sonodynamic therapy without recurrence. This drug system expands the application of endogenous cell to participate in drug delivery system. Thus, the assembly strategy demonstrates the potential of endogenous neutrophils in functioning as natural drug vehicles and the application of NIR-II fluorescent QDs in biomedical engineering.

Construction of PEGylated chlorin e6@CuS-Pt theranostic nanoplatforms for nanozymes-enhanced photodynamic-photothermal therapy

Multifunctional nanoagents with photodynamic therapy (PDT) and photothermal therapy (PTT) functions have shown great promise for cancer treatment, while the design and synthesis of efficient nanoagents remain a challenge. To realize nanozyme-enhanced PDT-PTT combined therapy, herein we have synthesized the Ce6@CuS-Pt/PEG nanoplatforms as a model of efficient nanoagents. Hollow CuS nanospheres with an average diameter of ∼ 200 nm are first synthesized through vulcanization using Cu2O as the precursor. Subsequently, CuS nanospheres are surface-decorated with Pt nanoparticles (NPs) as nanozyme via an in-situ reduction route, followed by modifying the DSPE-PEG5000 and loading the photosensitizer Chlorin e6 (Ce6). The obtained Ce6@CuS-Pt/PEG NPs exhibit high photothermal conversion efficiency (43.08%), good singlet oxygen (1O2) generation ability, and good physiological stability. In addition, Ce6@CuS-Pt/PEG NPs show good catalytic performance due to the presence of Pt nanozyme, which can effectively convert H2O2 to O2 and significantly enhance the production of cytotoxic 1O2. When Ce6@CuS-Pt/PEG NPs dispersion is injected into mice, the tumors can be wholly suppressed owing to nanozyme-enhanced PDT-PTT combined therapy, providing better therapeutic effects compared to single-mode phototherapy. Thus, the present Ce6@CuS-Pt/PEG NPs can act as an efficient multifunctional nanoplatform for tumor therapy.

A Smart Nano-Theranostic Platform Based on Dual-microRNAs Guided Self-Feedback Tetrahedral Entropy-Driven DNA Circuit.

MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors, capable of up or down-regulating gene expression during tumorigenesis; they are diagnostic biomarkers or therapeutic targets for tumors. To detect low abundance of intracellular oncogenic miRNAs (onco-miRNAs) and realize synergistic gene therapy of onco-miRNAs and tumor suppressors, a smart nano-theranostic platform based on dual-miRNAs guided self-feedback tetrahedral entropy-driven DNA circuit is created. The platform as a delivery vehicle is a DNA tetrahedral framework, in which the entropy-driven DNA circuit achieves a dual-miRNAs guided self-feedback, between an in situ amplification of the onco-miRNAs and activation of suppressor miRNAs release. To test this platform, dual-miRNAs are selected, miRNA-155, an up-regulated miRNA, as cancer indicators, and miRNA-122, a down-regulated miRNA as therapy targets in hepatocellular carcinoma, respectively. Through the circuit, the platform to detect onco-miRNAs at femtomolar level as well as visualized miRNAs inside cells, fixed tissues, and mice is programmed. Furthermore, triggered by miRNA-155, preloaded miRNA-122 is amplified via the self-feedback and released into target cells; the sudden increase of miRNA-122 and simultaneous decrease of miRNA-155 synergistically served as therapeutic drugs for gene regulation with enhanced antitumor efficacy and superior biosafety. It is envisioned that this nano-theranostic platform will initiate an essential step toward tumor theranostics in personalized/precise medicine.

Conjugated Polymer Nanoparticles for Tumor Theranostics.

Water-dispersible conjugated polymer nanoparticles (CPNs) have demonstrated great capabilities in biological applications, such as in vitro cell/subcellular imaging and biosensing, or in vivo tissue imaging and disease treatment. In this review, we summarized the recent advances of CPNs used for tumor imaging and treatment during the past five years. CPNs with different structures, which have been applied to in vivo solid tumor imaging (fluorescence, photoacoustic, and dual-modal) and treatment (phototherapy, drug carriers, and synergistic therapy), are discussed in detail. We also demonstrated the potential of CPNs as cancer theranostic nanoplatforms. Finally, we discussed current challenges and outlooks in this field.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer.

Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments.

NIR absorptive croconic acid/quercetin/CaO2 nanoplatform for tumor calcium overload therapy combined mild photothermal therapy

With excellent biocompatibility, stable chemical and optical properties, small organic molecules-based agents have always been a research hotspot in cancer photothermal therapy (PTT). In this work, a novel croconic acid-based molecule (CR) was designed and synthesized as an ideal photothermal agent (PTA), which showed abundant near-infrared (NIR) light absorption, high photothermal conversion ability, and excellent photothermal stability. By loading CR and quercetin (Qu) in CaO2, and coated with DSPE-PEG2000, a multifunctional theranostic nanoparticle (CCQ) was successfully prepared for calcium overloading mitochondrial metabolism inhibition synergetic mild PTT. Upon entering tumor microenvironment, CCQ can produce abundant H2O2 and a large amount of calcium ions, which lead to the imbalance of calcium concentration in the internal environment of tumor cells and induced mitochondrial apoptosis. With the existence of Qu, CCQ can effectively inhibit the expression of heat shock proteins (Hsp) during the PTT process, which weaken the heat resistance of tumors, ablate tumors at lower temperature (~45 °C), and reduce the damage to normal tissues. Guided by photoacoustic imaging (PAI), CCQ showed excellent multimodal therapeutic effect of tumors. This study provided a novel CR organic molecule-based theranostic nanoplatform that can be used to treat tumors via calcium overload therapy synergetic PTT at safe temperatures, which has promising potential for the future clinical cancer treatment.

Duplex Responsive Nanoplatform with Cascade Targeting for Atherosclerosis Photoacoustic Diagnosis and Multichannel Combination Therapy.

The culprits of atherosclerosis are endothelial damage, local disorders of lipid metabolism, and progressive inflammation. Early atherosclerosis is typically difficult to diagnose in time due to the lack of obvious symptoms, thus missing the best period of treatment. In this work, a π-conjugated polymer (PMeTPP-MBT) based on 3,6-bis(4-methylthiophen-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione is designed as a novel photoacoustic contrast agent. On this basis, an intelligent responsive theranostic nanoplatform (PA/ASePSD) combining astaxanthin and SS-31 peptide and loading with PMeTPP-MBT is developed. The high affinity between the dextran shell with the broken endothelial surface VCAM-1 and CD44 confers active targeting of PA/ASePSD to atherosclerotic lesions. High levels of ROS in the acidic plaque microenvironment act as an intelligent cascade switch to achieve controlled release of astaxanthin, SS-31 peptide, and PMeTPP-MBT for non-invasive photoacoustic diagnosis, as well as plaque inhibition mediated by anti-inflammation and multichannel regulation (including ABCA1, ABCG1, CD36, and LOX-1) of lipid metabolism. Both in vitro and in vivo evaluations confirm the impressive anti-atherosclerotic capability and the accurate photoacoustic diagnosis of PA/ASePSD nanoparticles, thus promising a candidate for early-stage atherosclerosis theranostics.

Recent development of pH-responsive theranostic nanoplatforms for magnetic resonance imaging-guided cancer therapy.

The acidic characteristic of the tumor site is one of the most well-known features and provides a series of opportunities for cancer-specific theranostic strategies. In this regard, pH-responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI-guided theranostic nanoplatforms for tumor-specific treatments.Therefore, various MRI-based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH-responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH-responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH-responsiveness for cancer diagnosis and therapy are discussed.

Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies.

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r2 = 416 s-1·mM-1, SARMH = 580 W·g-1, SARPTT = 800 W·g-1; and r2 = 407 s-1·mM-1, SARMH = 899 W·g-1, SARPTT = 300 W·g-1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells.

Gold cluster encapsulated liposomes: theranostic agent with stimulus triggered release capability

Cancer is a major cause of death worldwide. Cancer-resistant to chemo or radiotherapy treatment is a challenge that could be overcome by a nanotechnology approach. Providing a theranostic nano-platform for different cancer treatment strategies could be revolutionary. Here we introduce a multifunctional theranostic nanostructure which has the capacity for improving cancer diagnosis and treatment through better chemo and radiotherapy and current x-ray imaging systems through co-encapsulation of a small gold cluster and anticancer drug doxorubicin. 2nm gold clusters represent good heating under radio frequency electric field (RF-EF) exposure and have been used for in vitro hyperthermia treatment of cancerous cells. Liposomal doxorubicin (169 ± 19.8nm) with gold clusters encapsulation efficiency of 13.2 ± 3.0% and doxorubicin encapsulation efficiency of 64.7 ± 0.7% were prepared and studied as a theranostic agent with a high potential in different cancer treatment modalities. Exposure to a radiofrequency electric field on prepared formulation caused 20.2 ± 2.1% drug release and twice decreasing of IC50 on colorectal carcinoma cells. X-ray attenuation efficiency of the liposomal gold cluster was better than commercial iohexol and free gold clusters in different concentrations. Finally, treatment of gold clusters on cancerous cells results in a significant decrease in the viability of irradiated cells to cobalt-60 beam. Based on these experiments, we concluded that the conventional liposomal formulation of doxorubicin that has been co-encapsulated with small gold clusters could be a suitable theranostic nanostructure for cancer treatment and merits further investigation.

Enzyme-Activatable Polypeptide for Plasma Membrane Disruption and Antitumor Immunity Elicitation.

Enzyme-instructed self-assembly of bioactive molecules into nanobundles inside cells is conceived to potentially disrupt plasma membrane and subcellular structure. Herein, an alkaline phosphatase (ALP)-activatable hybrid of ICG-CF4 KYp is facilely synthesized by conjugating photosensitizer indocyanine green (ICG) with CF4 KYp peptide via classical Michael addition reaction. ALP-induced dephosphorylation of ICG-CF4 KYp enables its transformation from small-molecule precursor into rigid nanofibrils, and such fibrillation in situ causes severe mechanical disruption of cytomembrane. Besides, ICG-mediated photosensitization causes additional oxidative damage of plasma membrane by lipid peroxidation. Hollow MnO2 nanospheres devote to deliver ICG-CF4 KYp into tumorous tissue through tumor-specific acidity/glutathione-triggered degradation of MnO2 , which is monitored by fluorescent probing and magnetic resonance imaging. The burst release of damage-associated molecular patterns and other tumor antigens during therapy effectively triggers immunogenetic cell death and improves immune stimulatory, as demonstrated by the promotion of dendritic cell maturation and CD8+ lymphocyte infiltration, as well as constraint of regulatory T cell population. Taken together, such cytomembrane injury strategy based on peptide fibrillation in situ holds high clinical promise for lesion-specific elimination of primary, abscopal, and metastatic tumors, which may enlighten more bioinspired nanoplatforms for anticancer theranostics.

Magnetic Response Combined with Bioactive Ion Therapy: A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal Ischemia-Reperfusion Injury.

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia-reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe3O4 and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a "diagnosis-therapy-protection" approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.