Protein-coated cobalt oxide-hydroxide nanospheres deliver photosensitizer IR780 iodide for near-infrared light-triggered photodynamic/photothermal/chemodynamic therapy against colon cancer.

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.

A multifunctional nanotheranostic agent based on Lenvatinib for multimodal synergistic hepatocellular carcinoma therapy with remarkably enhanced efficacy.

Lenvatinib (LT), a first-line molecular targeted therapeutic drug for hepatocellular carcinoma (HCC), has been replacing the status of Sorafenib (SF) as the clinically preferred and irreplaceable treatment for a decade. To overcome the low drug utilization and limited single efficacy of LT, ultrasmall copper sulfide nanocrystals (Cu2-xS NCs), and ultrasmall gold nanoparticle (AuNPs) were evenly wrapped into galactosamine conjugated poly(lactide-co-glycolide) (PLGA) as the drug delivery nanoparticles (CAL@PG) by nanoprecipitation. The CAL@PG NPs exhibited excellent stability under physiological conditions, whereas they released LT rapidly in the unique tumor microenvironment (TME) and high temperature, which could be provided by the near-infrared-II (NIR-II) photothermal effect of Cu2-xS NCs. Moreover, the temperature elevation, regenerated hydrogen peroxide (H2O2), and lower pH of TME could substantially boost the reaction potency of copper Fenton-like chemistry. More importantly, this combined therapy significantly improved the efficacy of LT, provided a multifunctional LT delivery system, and enriched the nanoparticle-augmented multimodal synergistic HCC therapy modality.

Intelligent Bi2Se3@Cu2-xSe heterostructures with enhanced photoabsorption and photoconversion efficiency for tri-modal imaging guided combinatorial cancer therapy by near-infrared â ¡ light.

A novel nanoplatform that supports multimodal imaging has been designed for deep tumor therapy. In this study, Bi2Se3@Cu2-xSe heterojunction nanocomposites with tunable spectral absorption, effective electron-hole separation and high photothermal conversion efficiency were prepared for the combination therapy of phototherapy (PT), chemodynamic therapy (CDT) and radiotherapy (RT). By adjusting the doping ratio, the heterojunction nanoparticles show obvious tunable ability of local surface plasmon resonance and the ability to promote electron-hole separation with significantly enhanced reactive oxygen species production capacity. The band structure and charge density difference calculated by density functional theory further reveal that the change of band gap and the decrease of free carriers can regulate the spectral absorption of nanomaterials and promote electron-hole separation. In addition, the photothermal conversion properties of low carrier density semiconductors are related to their inherent deep level defects. The formation of heterojunctions making the Se atoms deviate from the Bi2Se3 lattice, resulting in more deep level defects and stronger photothermal conversion properties. Meanwhile, this nanoplatform presented features similar to catalase activities and glutathione (GSH) consumption characteristics, which was capable of effectively alleviate the tumor-specific hypoxia environment to enhance the efficacy of O2-dependent photodynamic therapy (PDT) and radiotherapy (RT) and depletion GSH to prevent the reduction of therapeutic efficacy due to the clearance of reactive oxygen species. In addition to therapeutic enhancement, heterojunction nanomaterials have excellent nuclear magnetic resonance imaging (MRI), infrared thermal imaging (IR) and computed tomography (CT) properties due to their significant paramagnetism and excellent photothermal conversion and X-ray attenuation capacities. In conclusion, our findings provide a new strategy for designing multi-function and efficient nanoplatform to treat tumor.

Achieving a "all in one" Fe/Tm-MOFs with controllable photothermal and catalytic performance for imaging-guided multi-modal synergetic therapy.

Targeting excess H2O2 in the tumor microenvironment, nanotheranostic agents for catalytic therapy are designed based on Fenton reaction, catalyzing H2O2 into oxygen and hydroxyl radical (OH). But the catalytic efficiency in tumor microenvironment is not satisfactory. In order to solve the problem, a series of bimetallic-dual ligands metal-organic frameworks Fe/Tm-MOFs were designed, that Fe3+ and Tm3+ as metalions, 2-methylimidazole and trimesic acid as ligands. Due to the doped Tm3+ in Fe/Tm-MOFs and the conjugated structures formed by two ligands, the rate of electron transfer was improved, thus promoting the generation of OH at some extent. In addition, the photothermal effect of Fe/Tm-MOFs further promotes the generation of OH, which was evidenced by the 3,3',5,5'-tetramethylbenzidine(TMB). Combining the drug loading and release capabilities of Fe/Tm-MOFs, synergetic therapy of photothermal/chemo-/catalytic therapy can be achieved. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive. In vivo anti-cancer results show that the tumors of mice almost disappeared within 10 days, which were injected with Fe/Tm-MOFs/DOX and irradiated with 808 nm for 10 min. Thus, an excellent therapeutic performance has been achieved. Besides, Fe/Tm-MOFs can serve as a multimodality bioimaging contrast agent, covering fluorescence imaging, photothermal imaging and magnetic resonance imaging. Thus, an all-in-one nanotheranostic agent is constructed, improving the catalytic efficiency and providing a novel method to design an efficient nanotheranostic agent.

Pt nanoenzyme decorated yolk-shell nanoplatform as an oxygen generator for enhanced multi-modality imaging-guided phototherapy.

The unsatisfactory efficacy of conventional theranostic agents in ablating tumor poses urgent demands on the development of high-performance integrated theranostic agents utilizing rising nanotechnology. To cope with the existing limitations, here we presented an intelligent nanoplatform based on yolk-shell Fe3O4@polydopamine prepared by mussel-inspired polydopamine chemistry and sacrificial template method as well as subsequent incorporation of Pt nanoparticles and chlorine 6 (Ce6) by in situ reduction and electrostatic adsorption for photodynamic therapy (PDT) and photothermal (PTT). The resultant nanoplatform could effectively deliver photosensitizer Ce6 to tumor sites, then promoting the decomposition of endogenous H2O2 to oxygen, finally achieving enhanced PDT therapy, which is demonstrated by in vitro and in vivo evaluations. Importantly, the generated oxygen bubbles could improve the echogenicity signal of yolk-shell microspheres and thereby provide enhanced ultrasonic (US) signal for imaging solid tumors. Overall, the synergistic combination of magnetic Fe3O4, green polydopamine, catalytic Pt nanoparticles, photosensitive Ce6 enabled the hybrid nanoplatform to have good biocompatibility, efficient tumor accumulation, excellent phototherapy efficiency, high T2-weighted magnetic resonance imaging (MRI) and fluorescence imaging ability (FL). Our study integrating the merits of PDT/PTT and US/MRI/FL into a single nanoplatform will open an avenue of therapeutic strategy toward biomedical applications.

Construction multifunctional nanozyme for synergistic catalytic therapy and phototherapy based on controllable performance.

Advances in nanozyme involve an efficient catalytic process, which has demonstrated great potential in tumor therapy. The key to improving catalytic therapy is to solve the limitation of the tumor microenvironment on Fenton reaction. In this work, Prussian blue nanoparticles doped with different rare earth ions (Yb3+, Gd3+, Tm3+) were screened to perform synergistic of photothermalandcatalytictumortherapy. The optimized catalytic performance can be further enhanced through photothermal effect to maximize the Fenton reaction to solve the limitation of the tumor microenvironment. Yb-PB, with the optimal photothermal and catalytic performance, was screened out. In order to avoid the scavenging effect of glutathione (GSH) on ·OH in tumor cells and the reaction with a bit H2O2 in normal cells, GSH targeted polydopamine (PDA) was wrapped on the surface of Yb-PB to obtain Yb-PB@PDA. It was found that enough hydroxyl radicals (·OH) can be generated even if at high GSH concentration and the NIR irradiation can help produce more ·OH. Cell fluorescence imaging (FOI) and in vivo magnetic resonance imaging (MRI) experiments showed the potential application in FOI/MRI dual-mode imaging guided therapy. In vivo anti-tumor experiments showed that Yb-PB@PDA has a satisfactory anti-cancer effect through the combined effect of catalytic/photothermal therapy. Thus, a multifunctional nanozyme for tumor therapy is constructed.

Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.

Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.

"Dual-Key-and-Lock" dual drug carrier for dual mode imaging guided chemo-photothermal therapy.

Drug resistance and side effects are the two main problems of chemotherapy. In order to address these big challenges, p-PB@d-SiO2, which has the ability to co-deliver both the hydrophobic drug doxorubicin hydrochloride (DOX) and the hydrophilic drug ibuprofen (IBU), is constructed to achieve synergistic treatment. The drug-loaded nanoparticle consists of porous Prussian blue (p-PB) as the core and dendrimer-like SiO2 (d-SiO2) as the shell, which is further thiolated and coated with polyethylene glycol thiol (HS-PEG) to form the "Dual-Key-and-Lock" drug carrier p-PB@d-SiO2-SS-PEG. The locked drugs can only be released in the presence of cooperative triggers, i.e., a high glutathione concentration (the first key) and an acidic environment (the second key). The "dual key"-triggered release is much more significant in cancer lesions than in normal tissues, reducing side effects. Furthermore, cell viability experiments highlight the superior therapeutic efficacy of the dual-drug-loaded nanoparticles compared with the single-drug systems (60%, 73% and 86% vs. 56%, 68%, and 76% at 100, 200 and 500 µg mL-1, respectively). In vitro and in vivo experiments demonstrate the potential application of p-PB@d-SiO2-SS-PEG for dual-mode fluorescence and magnetic-resonance-imaging-guided chemo-photothermal therapy. The "Dual-Key-and-Lock" drug carrier system exhibits the "1 + 1 > 2" effect, demonstrating its excellent performance in synergy therapy for improved therapeutic efficiency and thereby reducing conventional drug resistance and side effects.

Co-delivery of Bee Venom Melittin and a Photosensitizer with an Organic-Inorganic Hybrid Nanocarrier for Photodynamic Therapy and Immunotherapy.

Photodynamic therapy (PDT) is a clinical cancer treatment modality based on the induction of therapeutic reactive oxygen species (ROS), which can trigger immunogenic cell death (ICD). With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels, we designed a serum albumin (SA)-coated boehmite ("B"; aluminum hydroxide oxide) organic-inorganic scaffold that could be loaded with chlorin e6 (Ce6), a photosensitizer, and a honey bee venom melittin (MLT) peptide, denoted Ce6/MLT@SAB. Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm. Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT, while providing MLT-enhanced PDT antitumor effects in vitro. Compared with Ce6@SAB, Ce6/MLT@SAB improved Ce6 penetration of cancer cells both in vitro and in vivo, thereby providing enhanced intracellular ROS generation with 660 nm light treatment. Following phototreatment, Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells. In the absence of laser irradiation, multidose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%, compared to controls. When combined with laser irradiation, a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice. The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented antitumor effects, generating increased numbers of CD4+ and CD8+ T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.

H2O2/near-infrared light-responsive nanotheronostics for MRI-guided synergistic chemo/photothermal cancer therapy.

Aim: To develop a H2O2/near-infrared (NIR) laser light-responsive nanoplatform (manganese-doped Prussian blue@polypyrrole [MnPB@PPy]) for synergistic chemo/photothermal cancer theranostics. Materials & methods: Doxorubicin (DOX) was loaded onto the surface of polypyrrole shells. The in vitro and in vivo MRI performance and anticancer effects of these nanoparticles (NPs) were evaluated. Results: The MnPB@PPy NPs could not only generate heat under NIR laser irradiation for cancer photothermal therapy but also act as an excellent MRI contrast agent. The loaded DOX could be triggered to release by both NIR light and H2O2 to enhance synergistic therapeutic efficacy. The antitumor effects were confirmed by in vitro cellular cytotoxicity assays and in vivo treatment in a xenograft tumor model. Conclusion: The designed H2O2/NIR light-responsive MnPB@PPy-DOX NPs hold great potential for future biomedical applications.

Polydopamine-mediated bio-inspired synthesis of copper sulfide nanoparticles for T1-weighted magnetic resonance imaging guided photothermal cancer therapy.

Copper sulfide nanoparticles(CuS NPs) have attracted considerable interest in the field of photothermal therapy(PTT) due to its low cost, easy preparation and favorable photothermal effect. However, lack of reliable visualization and relatively poor biocompatibility restrict its further bio-application. To overcome these limitations, polydopamine(PDA, a melanin-like biopolymer) stabilized CuS NPs and further chelated with iron ions (denoted as CuPDF) were designed as a versatile nanoplatform for T1-weighted MR imaging-guided PTT. In this system, PDA served as both bio-template to synthesis CuS NPs and an active platform to give MRI diagnostic capability. The as-prepared CuPDF NPs demonstrated strong absorption at NIR region, nearly three times higher than that of pure PDA NPs at 808 nm. Moreover, toxicity studies and histology evalution verified that CuPDF NPs possess excellent biocompatibility. In addition, CuPDF NPs showed significant MRI signal enhancement with high longitudinal relaxivity (r1 = 4.59 mM-1 s-1). In vivo MRI and biodistribution test confirmed the efficient accumulation of CuPDF NPs in the tumor region. After intravenous injection of CuPDF, irreversible tumor ablation was successfully achieved without inducing any obvious side effects by using 808-nm laser irradiation. All in all, these results indicated that the developed CuPDF NPs hold great potential as an effective theranostic agent for MR imaging guided PTT in vivo.

One-pot synthesis of albumin-gadolinium stabilized polypyrrole nanotheranostic agent for magnetic resonance imaging guided photothermal therapy.

Theranostic agents with perfect properties are needed urgently for the development of imaging guided photothermal therapy (PTT). In this work, Gd-integrated polypyrrole nanotheranostic agent (PPy@BSA-Gd) was successfully built through selecting bovine serum albumin (BSA) as both stabilizers for polymerization and biomimetic mineralization in "one pot". The obtained PPy@BSA-Gd possessed high stability and excellent photothermal property. Besides, relevant cellular assays indicated that PPy@BSA-Gd had fantastic cytocompatibility which could be further internalized by cancer cells. Due to their high longitudinal relaxivity value (r1 = 10.203 mM-1 s-1), PPy@BSA-Gd could serve as considerable probe for T1-weighted magnetic resonance imaging (MRI). After tail vein injection of PPy@BSA-Gd, the MR signal of tumor section exhibited a time-dependent increase, indicating effective tumor accumulation of PPy@BSA-Gd. Notably, when exposed to 808 nm laser, the tumor growth of PPy@BSA-Gd treated mice could be inhibited by photothermal ablation successfully. All the results demonstrated the well-designed PPy@BSA-Gd have the potential for tumor diagnose and photothermal therapy.