Porous Gold Nanoshells on Functional NH2 -MOFs: Facile Synthesis and Designable Platforms for Cancer Multiple Therapy.

AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH2 -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH2 -MOFs@Aushell ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH2 -MOFs with those of porous gold nanoshells. Moreover, in order to illustrate the promising applications of this method in biomedicine, platinum nanozymes-encapsulated NH2 -MOFs are further designed with porous gold nanoshell coating and photosensitizer chlorin e6 (Ce6)-loaded nanoparticles with continuous O2 -evolving ability (Pt@UiO-66-NH2 @Aushell -Ce6). The combination of photodynamic and photothermal therapy is then carried out both in vitro and in vivo, achieving excellent synergistic therapeutic outcomes. Therefore, this work not only presents a facile strategy to fabricate functionalized porous gold nanoshell structures, but also illustrates an excellent synergistic tumor therapy strategy.

A rapid and convenient method for detecting a broad spectrum of malignant cells from malignant pleuroperitoneal effusion of patients using a multifunctional NIR heptamethine dye.

Detection of malignant cells from malignant effusion is crucial to establish or adjust therapies of patients with cancer. The conventional qualitative detection in malignant pleuroperitoneal effusion is cytological analysis, which is time-consuming and complicated. Therefore, a faster and more convenient detection strategy is urgently needed. In this study, we report a rapid method to detect malignant cells from malignant pleuroperitoneal effusion (hydrothorax and ascites) of patients using IR-808, a tumor-targeted near-infrared (NIR) fluorescent heptamethine dye (tNRI dye), which exhibited superior labeling efficacy without specific conjugation to biomarkers. The targeted imaging performance toward malignant cells using IR-808 was confirmed by comparing with normal cells, and the fluorescence stability assay of IR-808 in malignant effusion was performed from 1 h to 48 h. In order to save time and dose, the incubation time and concentration were optimized to 10 min and 5 µM, which were used to detect malignant cells from 28 clinical samples of malignant pleuroperitoneal effusion. The results revealed that IR-808 could be internalized selectively by malignant cells of samples, and these malignant cells could be easily distinguished from normal cells under a fluorescence microscope. The positive rates between cytological analysis and the IR-808 staining method were 86% (24/28) and 79% (22/28), respectively. An excellent concordance level (Kappa = 0.752, P < 0.001) was observed between the two methods. Our results indicated that IR-808, a new NIR fluorescent heptamethine dye with unique optical imaging and tumor targeting properties, could provide a fast and simple way to detect a broad spectrum of malignant cells from malignant pleuroperitoneal effusion in patients.

Photothermal-promoted O2/OH generation of gold nanotetrapod @ platinum nano-islands for enhanced catalytic/photodynamic therapy.

Ultrasmall platinum (Pt) nanozymes are used for catalytic therapy and oxygen (O2)-dependent photodynamic therapy (PDT) by harnessing the dual-enzyme activities of catalase (CAT) and peroxidase (POD). However, their applications as nanocatalysts are limited due to their low catalytic activity. Herein, we constructed a photothermal-promoted bimetallic nanoplatform (AuNTP@Pt-IR808) by depositing ultrasmall Pt nano-islands and modifying 1-(5-Carboxypentyl)-2-(2-(3-(2-(1-(5-carboxypentyl)-3,3-dimethylindolin-2-ylidene)ethylidene)-2-chlorocyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-3H-indol-1-ium bromide (IR808) on gold nanotetrapod (AuNTP) with CAT/POD activities to enhance PDT/catalytic therapy. In the tumor microenvironment, the ultrasmall Pt can catalyze endogenous hydrogen peroxide (H2O2) to produce O2, relieving tumor hypoxia and enhancing the PDT performance. Moreover, AuNTP integration into the bimetallic nanoplatform showed good electron transfer properties and promoted the POD activity of ultrasmall Pt. Importantly, AuNTP@Pt-IR808 possessed higher photothermal conversion performance than single AuNTPs, which enhanced photothermal therapy (PTT). It also accelerated the CAT/POD dual-enzyme activities, and promoted the generation of singlet oxygen (1O2) and hydroxyl radical (OH). By enhancing the performances of PTT/PDT/catalytic therapy, the developed AuNTP@Pt-IR808 nanoplatform demonstrated good antitumor efficacy against breast cancer.

Biodegradable hollow mesoporous bimetallic nanoreactors to boost chemodynamic therapy.

As an endogenous catalytic treatment, chemodynamic therapy (CDT) was attracting considerable attention, but the weak catalytic efficiency of Fenton agents and the non-degradation of nanocarriers severely limited its development. In this work, a biodegradable bimetallic nanoreactor was developed for boosting CDT, in which Fe-doped hollow mesoporous manganese dioxide (HMnO2) was selected as nanocarrier, and the Fe/HMnO2@DOX-GOD@HA nanoprobe was constructed by loading doxorubicin (DOX) and modifying glucose oxidase (GOD) and hyaluronic acid (HA). The glutathione (GSH) responsive degradation of HMnO2 promoted the release of DOX, by which the release rate significantly increased to 96.6%. Moreover, by the GSH depletion, the reduction of Mn2+/Fe2+ achieved strong bimetallic Fenton efficiency, and the hydroxyl radicals (·OH) generation was further enhanced using the self-supplying H2O2 of GOD. Through the active targeting recognition of HA, the bimetallic nanoreactor significantly enriched the tumor accumulation, by which the enhanced antitumor efficacy was realized. Thus, this work developed biodegradable bimetallic nanoreactor by consuming GSH and self-supplying H2O2, and provided a new paradigm for enhancing CDT.

Mesoporous polydopamine delivery system for intelligent drug release and photothermal-enhanced chemodynamic therapy using MnO2 as gatekeeper.

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors.

Ultrasmall gold decorated bimetallic metal-organic framework based nanoprobes for enhanced chemodynamic therapy with triple amplification.

Chemodynamic therapy (CDT) has shown potential for important applications in tumor precision therapy, but insufficient endogenous hydrogen peroxide (H2O2), overexpressed glutathione (GSH) and a weak Fenton-reaction rate greatly reduced the efficacy of CDT. Herein, a metal-organic framework (MOF) based bimetallic nanoprobe with self-supplying H2O2 was developed for enhancing CDT with triple amplification, in which ultrasmall gold nanoparticles (AuNPs) were deposited on Co-based MOFs (ZIF-67), and manganese dioxide (MnO2) nanoshells were coated to form a ZIF-67@AuNPs@MnO2 nanoprobe. In the tumor microenvironment, MnO2 depleted overexpressed GSH to produce Mn2+, and the bimetallic Co2+/Mn2+ nanoprobe accelerated the Fenton-like reaction rate. Moreover, by catalyzing glucose via ultrasmall AuNPs, the self-supplying H2O2 further promoted hydroxyl radical (˙OH) generation. Compared with those of ZIF-67 and ZIF-67@AuNPs, the ˙OH yield of ZIF-67@AuNPs@MnO2 obviously increased, due to which the cell viability decreased to 9.3%, and the tumor completely disappeared, indicating the enhanced CDT performance of the ZIF-67@AuNPs@MnO2 nanoprobe.

Colorimetric sensor for Cr (VI) by oxidative etching of gold nanotetrapods at room temperature.

Hexavalent chromium (Cr(VI)) is highly carcinogenic and mutagenic, which is seriously harmful to human health. Hence, it is important to create a probe that can detect Cr(VI) effectively. In this work, gold nanotetrapods (Au NTPs) were applied in colorimetric detection for the first time. Based on the oxidative etching principle of Cr(VI) on Au NTPs, a sensitive and multicolor response detection method for Cr(VI) was established. The oxidative etching of Au NTPs by Cr(VI) resulted in the blue shift of plasmon resonance absorption peak of Au NTPs with the change of morphology. As the etching progress processed, Au NTPs solution exhibited obvious color changes from gray-green to blue-violet and then to pink. This multicolor response design is very convenient for naked-eye detection. The limit of detection (LOD) of Cr(VI) is 3 nM for the naked eyes and 0.5 nM for UV-vis spectrum, both of which are lower than the toxicity level of Cr(VI) (0.2 µM) set by United States Environmental Protection Agency. This sensing method exhibits good linearity between the wavelength shift and Cr(VI) concentration in the range of 0.5 nM to 8 nM. The detection results of Cr(VI) in actual environmental samples demonstrate that the Au NTPs colorimetric probe (Au-N-Probe) is expected to be applied to the detection of Cr(VI) in water environmental samples such as lake water and industrial wastewater.

Ultrasmall water-soluble metal-iron oxide nanoparticles as T1-weighted contrast agents for magnetic resonance imaging.

Using an improved hydrolysis method of inorganic salts assisted with water-bath incubation, ultrasmall water-soluble metal-iron oxide nanoparticles (including Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles) were synthesized in aqueous solutions, which were used as T(1)-weighted contrast agents for magnetic resonance imaging (MRI). The morphology, structure, MRI relaxation properties and cytotoxicity of the as-prepared metal-iron oxide nanoparticles were characterized, respectively. The results showed that the average sizes of nanoparticles were about 4 nm, 4 nm and 5 nm for Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles, respectively. Moreover, the nanoparticles have good water dispersibility and low cytotoxicity. The MRI test showed the strong T(1)-weighted, but the weak T(2)-weighted MRI performance of metal-iron oxide nanoparticles. The high T(1)-weighted MRI performance can be attributed to the ultrasmall size of metal-iron oxide nanoparticles. Therefore, the as-prepared metal-iron oxide nanoparticles with good water dispersibility and ultrasmall size can have potential applications as T(1)-weighted contrast agent materials for MRI.

Dye surface coating enables visible light activation of TiO2 nanoparticles leading to degradation of neighboring biological structures.

Biologically and chemically modified nanoparticles are gaining much attention as a new tool in cancer detection and treatment. Herein, we demonstrate that an alizarin red S (ARS) dye coating on TiO2 nanoparticles enables visible light activation of the nanoparticles leading to degradation of neighboring biological structures through localized production of reactive oxygen species. Successful coating of nanoparticles with dye is demonstrated through sedimentation, spectrophotometry, and gel electrophoresis techniques. Using gel electrophoresis, we demonstrate that visible light activation of dye-TiO2 nanoparticles leads to degradation of plasmid DNA in vitro. Alterations in integrity and distribution of nuclear membrane associated proteins were detected via fluorescence confocal microscopy in HeLa cells exposed to perinuclear localized ARS-TiO2 nanoparticles that were photoactivated with visible light. This study expands upon previous studies that indicated dye coatings on TiO2 nanoparticles can serve to enhance imaging, by clearly showing that dye coatings on TiO2 nanoparticles can also enhance the photoreactivity of TiO2 nanoparticles by allowing visible light activation. The findings of our study suggest a therapeutic application of dye-coated TiO2 nanoparticles in cancer research; however, at the same time they may reveal limitations on the use of dye assisted visualization of TiO2 nanoparticles in live-cell imaging.

Advances of Light/Ultrasound/Magnetic-Responsive Nanoprobes for Visualized Theranostics of Urinary Tumors.

Light/ultrasound/magnetic-responsive nanomaterials exhibit excellent performance in imaging and therapy and play an important role in precision theranostics of tumors. In contrast to deep organs, urinary organs (such as bladder and prostate) can easily be studied via intervention mode, which has greatly brought promising applications of stimuli-responsive nanoprobes in visualized theranostics of urinary tumors. Therefore, it has been very critical to develop stimuli-responsive nanoprobes with high safety, stability, and reliability against urinary tumors. In this review, recent advances in light/ultrasound/magnetic-responsive nanoprobes in visualized theranostics of urinary tumors are summarized, including magnetic resonance/fluorescence/ultrasound/photoacoustic imaging and multimodal imaging, photothermal/photodynamic/sonodynamic therapy and combination therapy, and single-modal/multimodal-imaging-guided visualized theranostics. Finally, the future perspectives of light/ultrasound/magnetic-responsive nanoprobes against urinary tumors are also prospected.

Endo/exo-genous dual-stimuli responsive gold nanotetrapod-based nanoprobe for magnetic resonance imaging and enhanced multimodal therapeutics by amplifying·OH generation.

Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H2O2) seriously restricted its application. Herein, using endo/exo-genous dual-stimuli, a novel nanoprobe with enhanced ·OH generation was developed for magnetic resonance (MR) imaging and multimodal therapeutics, in which gold nanotetrapod (AuNTP) with photothermal therapy (PTT) performance was coated with mesoporous silica (mSiO2) and loaded with cisplatin (CDDP), then a thin layer of manganese dioxide (MnO2) was deposited to construct AuNTP@mSiO2@CDDP@MnO2 nanoprobes. In TME, endogenous H2O2, CDDP-triggered self-supplying H2O2 produced via cascade reaction and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation of Mn2+ induced by glutathione (GSH) responsive degradation of MnO2. The prepared AuNTP@mSiO2@CDDP@MnO2 nanoprobes possessed perfect core@shell structure, good biocompatibility and GSH-dependent MR performance, in which the relaxation rates increased from 0.717 mM-1·s-1 to 8.12 mM-1·s-1. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO2@CDDP@MnO2 nanoprobes demonstrated good antitumor efficacy. Our work provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced visualized theranostics of tumors. STATEMENT OF SIGNIFICANCE: Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) can produce high-toxic hydroxyl radicals (·OH) to kill cancer cells, but the limited concentration of endogenous hydrogen peroxide (H2O2) seriously restricted its application. Using endo/exo-genous dual-stimuli, AuNTP@mSiO2@CDDP@MnO2 (AMCM) nanoprobe was constructed, in which endogenous H2O2, CDDP-triggered self-supplying H2O2 and the exogenous photothermal effect of AuNTPs together enhanced the ·OH generation. Under the multimodal therapeutics of CDT/PTT/chemotherapy, the developed AuNTP@mSiO2@CDDP@MnO2 nanoprobe demonstrated good antitumor efficacy, and provided a promising strategy for constructing TME-responsive nanoprobes with endo/exo-genous stimuli, achieving enhanced CDT of tumors.

Ultrasmall Gold-Coated Mesoporous Polydopamine Nanoprobe to Enhance Chemodynamic Therapy by Self-Supplying H2O2 and Photothermal Stimulation.

Tumor microenvironment (TME) responsive chemodynamic therapy (CDT) showed an important application in inhibiting tumor growth by producing the highly toxic hydroxyl radical (·OH), but insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH) limited its application. Herein, by integrating photothermal therapy (PTT) and CDT, a new kind of mesoporous polydopamine (MPDA)-based cascade-reaction nanoplatform (MPDA@AuNPs-Cu) was designed for enhanced antitumor therapy, in which ultrasmall gold nanoparticles (AuNPs) with glucose oxidase (GOx)-like activity were deposited on MPDA for providing H2O2, and Cu2+ was chelated for GSH-responsive Fenton-like reaction. It was demonstrated that the MPDA@AuNPs-Cu nanoprobe showed high photothermal conversion efficiency and excellent biocompatibility. Moreover, the MPDA@AuNPs-Cu nanoprobe exhibited strong ·OH generation because of H2O2 self-generation and photothermal stimulation. Importantly, compared with MPDA-Cu, MPDA@AuNPs-Cu exhibited enhanced in vitro and in vivo CDT/PTT performance, by which the tumor growth was completely inhibited, achieving TME-responsive antitumor efficacy.

A one-step colorimetric method of analysis detection of Hg2+ based on an in situ formation of Au@HgS core-shell structures.

A new approach for the detection of Hg(2+) is reported based on color changes from which gold nanoparticles (Au NPs) are surrounded by a layer of HgS quantum dots to form in situ Au@HgS core-shell nanostructures. The surface plasmon resonance (SPR) absorption of the gold core was changed due to a shell layer of HgS formed on the surface of the Au NPs, which brings the colour change of the aqueous solution. Therefore, Hg(2+) can be recognized by visualizing the colour change of the Au@HgS core-shell nanostructures, and can be detected quantitatively by measurement of the UV-vis spectra. Some effects on the detection of Hg(2+) were investigated in detail. This method was used to detect Hg(2+) with excellent selectivity and high sensitivity. In our method, the lowest detected concentrations for mercury ions were 5.0 × 10(-6) M observed by the naked eye and 0.486 nM as measured by UV-vis spectra. At the range from 8.0 × 10(-5) to 1.0 × 10(-8) M of Hg(2+), this method was shown to have a good linear relationship.

H2O2-Responsive Gold Nanoclusters @ Mesoporous Silica @ Manganese Dioxide Nanozyme for "Off/On" Modulation and Enhancement of Magnetic Resonance Imaging and Photodynamic Therapy.

In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O2-generated nanozyme with intelligent "off/on" modulation and enhancement. Herein, a kind of H2O2-responsive nanozyme was developed for off/on modulation and enhancement of magnetic resonance (MR) imaging and PDT, in which great amounts of gold nanoclusters (AuNCs) were loaded into mesoporous silica to form nanoassembly, and manganese dioxide (MnO2) nanosheets were wrapped as switching shield shell (AuNCs@mSiO2@MnO2). In a neutral physiological environment, stable MnO2 shells eliminated singlet oxygen (1O2) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO2 shell reacted with H2O2, in which MnO2 degradation switched on MR imaging and PDT, and the generated O2 further enhanced PDT. H2O2-responsive MnO2 degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM-1 s-1, and simultaneously sufficient O2 generation guaranteed a 74% high 1O2 yield. Under the irradiation of a 635 nm laser, the viability of MDA-MB-435 cells was reduced to 4%, and the tumors completely disappeared, demonstrating strong PDT performance. Therefore, H2O2-responsive AuNCs@mSiO2@MnO2 nanozyme showed excellent off/on modulation and enhancement of MR imaging and PDT and was a promising intelligent nanoprobe for safe and high-efficiency theranostics.

Manganese-Doped Carbon Dots with Redshifted Orange Emission for Enhanced Fluorescence and Magnetic Resonance Imaging.

Metal-doped carbon dots (CDs) exhibited promising application in fluorescence and magnetic resonance (MR) imaging, but developing manganese-doped CDs (Mn-CDs) with long wavelength emission and enhanced MR performance is a challenge. Herein, using a one-step solvothermal method, Mn-CDs with redshifted orange emission and enhanced longitudinal relaxation were synthesized for fluorescence and MR imaging. The results indicated that the prepared Mn-CDs had a uniform size distribution, and the average size was 5 nm. Moreover, Mn-CDs possessed a stronger fluorescence performance than Mn-free CDs, and simultaneously, the emission wavelength can redshift from 542 nm (green emission) to 578 nm (orange emission), owing to the increasing N-doping. Because of the movement limit of Mn2+, Mn-CDs exhibited high T1-weighted MR imaging performance with a longitudinal relaxation rate of 12.69 mM-1·s-1. The in vivo experiments demonstrated their excellent fluorescence and MR imaging with safety and reliability. Therefore, the prepared Mn-CDs with orange emission can be an excellent candidate as a dual-modal nanoprobe for fluorescence and MR imaging.

Black titanium dioxide@manganese dioxide for glutathione-responsive MR imaging and enhanced photothermal therapy.

Multifunctional nanoprobes with tumor microenvironment response are playing important roles in highly efficient theranostics of cancers. Herein, a kind of theranostic nanoprobe was synthesized by coating manganese dioxide (MnO2) on the surface of black commercial P25 titanium dioxide (b-P25). The resultant nanoprobe (b-P25@MnO2) possessed glutathione (GSH)-responsive magnetic resonance (MR) imaging and enhanced photothermal therapy (PTT). In tumor microenvironments, the excessive GSH was consumed by reacting with MnO2 to generate Mn2+ for GSH-responsive MR imaging, in which the longitudinal relaxation rate of b-P25@MnO2 was up to 30.44 mM-1 s-1, showing excellent cellular and intratumoral MR imaging. Moreover, the prepared b-P25@MnO2 exhibited stable and strong photothermal conversion capability with a high photothermal conversion efficiency of 30.67%, by which the 4T1 tumors disappeared completely, indicating safe and highly efficient PTT performance. The current work developed GSH-responsive b-P25@MnO2 nanoprobes, demonstrated for MR imaging and enhanced PTT in cancers.

pH-Responsive metal-organic framework encapsulated gold nanoclusters with modulated release to enhance photodynamic therapy/chemotherapy in breast cancer.

Gold nanoclusters (AuNCs) with an ultra-small size, as new inorganic photosensitizers, have been shown to be promising in photodynamic therapy (PDT), but their application has been restricted due to short blood circulation. It is therefore important to develop stimuli-responsive AuNC-based nanoprobes to achieve highly efficient PDT. Here, metal-organic framework (MOF, ZIF-8) encapsulated AuNCs (AuNCs@MOF) were synthesized, and then they were loaded with doxorubicin (DOX) to obtain pH-responsive nanoprobes (AuNCs@MOF-DOX) with modulated release for enhanced PDT/chemotherapy. In an acidic tumor microenvironment, the structure of ZIF-8 collapsed, accelerating the release of the AuNCs and DOX in the tumor cells, and enhancing the performance of PDT/chemotherapy. Under irradiation with a 670 nm laser, a large amount of singlet oxygen was generated, and the release rate of DOX increased to 77.1% at a pH value of 5.5. By single PDT and single chemotherapy, the tumors were only partially inhibited, but they completely disappeared using the combination of PDT and chemotherapy. The prepared pH-responsive AuNCs@MOF-DOX nanoprobes with modulated release showed excellent PDT/chemotherapy performance, and will be important bi-functional nanoprobes for synergistic therapy.

Ce6-Conjugated and polydopamine-coated gold nanostars with enhanced photoacoustic imaging and photothermal/photodynamic therapy to inhibit lung metastasis of breast cancer.

Metastasis is the main cause of treatment failure in breast cancer, and integrated phototheranostics is a promising strategy to achieve both precision theranostics and metastasis inhibition. In this work, a multifunctional phototheranostic nanoprobe composed of chlorin e6 (Ce6)-conjugated and polydopamine (PDA)-coated gold nanostars (AuNSs) was synthesized for simultaneous photoacoustic (PA) imaging, photothermal therapy (PTT) and photodynamic therapy (PDT). Under the irradiation of near infrared laser, AuNSs@PDA showed enhanced photothermal conversion and amplified PA imaging performance, compared with single AuNSs. By the covalent conjugation of Ce6, the AuNSs@PDA-Ce6 nanoprobe showed robust stability and excellent singlet oxygen (1O2) generation ability. Under the combination of PTT/PDT, the AuNSs@PDA-Ce6 nanoprobes significantly reduced the growth of 4T1 tumors and suppressed their lung metastasis. All the results demonstrated the considerable potential of AuNSs@PDA-Ce6 phototheranostic nanoprobes for precision theranostics and metastasis inhibition of breast cancer.

Amplified Photoacoustic Signal and Enhanced Photothermal Conversion of Polydopamine-Coated Gold Nanobipyramids for Phototheranostics and Synergistic Chemotherapy.

Light-responsive nanoprobes were suffering from the threat of high-dose laser irradiation, and it was important for constructing new nanoprobes for safe and efficient phototheranostics. Here, polydopamine (PDA)-coated gold nanobipyramids (AuNBPs@PDA) were synthesized for amplified photoacoustic (PA) signal and enhanced photothermal conversion with low-dose laser irradiation and then doxorubicin (DOX)-loaded AuNBPs@PDA-DOX nanoprobes were constructed for PA imaging-guided synergistic photothermal therapy (PTT) and chemotherapy. The AuNBPs@PDA nanoparticles possessed higher photothermal conversion efficiency (42.07%) and stronger PA signal than those of AuNBP nanoparticles, and the AuNBPs@PDA-DOX nanoprobes showed dual-responsive DOX release of pH and photothermal stimulation. With low-dose laser irradiation (1.0 W/cm2) and low-concentration AuNBPs@PDA-DOX (60 µg/mL), the 4T1 cell viability was reduced to about 5%, owing to the combination of PTT and chemotherapy, compared with 42.3% of single chemotherapy and 25.3% of single PTT. Moreover, by modeling 4T1 tumor-bearing nude mice, in vivo PA imaging was achieved and the tumors were completely inhibited, demonstrating the excellent synergistic effect of PTT/chemotherapy. Therefore, the developed AuNBPs@PDA-DOX nanoprobes can be used for phototheranostics and synergistic chemotherapy, achieving low-dose laser irradiation and high-efficient visualized theranostics.