Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Rational Design of Dynamically Super-Tough and Super-Stretchable Hydrogels for Deformable Energy Storage Devices.

Hydrogels possess unique polymer networks that offer flexibility/stretchability, high ionic conductivity, and resistance to electrolyte leakage, making them suitable for deformable energy storage devices. Endowing the mechanical functionality of the hydrogel electrolytes focus on either enhancing the stretchability or the toughness. However, the stretchability and the toughness are generally a trade-off that the stretchable gels are intrinsically prone to damage and sensitive to notches and cracks. Here, the regulating strategies on the hydrogel's mechanical properties are provided to develop the designated hydrogel electrolyte, where different polymeric network structures are constructed, including single network structures, semi-interpenetrating network structures, and interpenetrating dual-network structures. A comprehensive comparison of these polymer network structures is conducted to evaluate their mechanical stretchability and toughness. Designing super-tough and super-stretchable hydrogels based on specific application requirements can be realized by striking a balance by regulating the hydrogel structure. In specific, incorporating semi-interpenetrating networks significantly can enhance stretchability to achieve a break elongation up to 1300%, while the interpenetrating dual-networks can largely improve the toughness to realize the extraordinary fracture toughness of 6.843 kJ m-2. These findings offer valuable designing guidance for designated hydrogel electrolytes and the deformable zinc-silver battery is demonstrated with high mechanical stability and electrochemical performance.

Mn(II) Optimized Sono/Chemodynamic Effect of Porphyrin-Metal-Organic Framework Nanosheets for MRI-Guided Colon Cancer Therapy and Metastasis Suppression.

Sonodynamic therapy (SDT) offers a remarkable non-invasive ultrasound (US) treatment by activating sonosensitizer and generating reactive oxygen species (ROS) to inhibit tumor growth. The development of multifunctional, biocompatible, and highly effective sonosensitizers remains a current priority for SDT. Herein, the first report that Mn(II) ions chelated Gd-TCPP (GMT) nanosheets (NSs) are synthesized via a simple reflux method and encapsulated with pluronic F-127 to form novel sonosensitizers (GMTF). The GMTF NSs produce a high yield of ROS under US irradiation due to the decreased highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy (2.7-1.28 eV). Moreover, Mn(II) ions endow GMTF with a fascinating Fenton-like activity to produce hydroxyl radicals in support of chemodynamic therapy (CDT). It is also effectively used in magnetic resonance imaging (MRI) with high relaxation rate (r 1: 4.401 mM-1 s-1) to track the accumulation of NSs in tumors. In vivo results indicate that the SDT and CDT in combination with programmed cell death protein 1 antibody (anti-PD-1) show effective metastasis prevention effects, and 70% of the mice in the GMTF + US + anti-PD-1 group survived for 60 days. In conclusion, this study develops a sonosensitizer with promising potential for utilizing both MRI-guided SDT and CDT strategies.

Dual-targeting nanotheranostics for MRI-guided enhanced chemodynamic therapy of hepatoma via regulating the tumor microenvironment.

Chemodynamic therapy (CDT), as a reactive oxygen species (ROS)-based therapeutic modality, has attracted much attention in recent years. However, the insufficient therapeutic effect of CDT is due to the antioxidant system in the tumor microenvironment, such as high levels of glutathione (GSH). In this study, we developed a biological/physical dual-targeting nanotheranostic agent (relaxation rate, r1: 6.3 mM-1 s-1 and r2: 13.11 mM-1 s-1) for enhanced CDT of SMCC-7721 tumors. This nanotheranostic agent is composed of a homologous tumor cell membrane (TCM), magnetic ferric oxide, and manganese oxide and is denoted as FM@TCM nanoparticles (NPs). A favorable effect of in vitro CDT on SMCC-7721 cells (IC50: 20 µg mL-1) is demonstrated, attributed to the Fenton reaction and oxidative stress resulting from the reduction of the GSH level. In vivo T1/T2 magnetic resonance imaging (MRI) confirms that the tumor accumulation of FM@TCM NPs is promoted by concurrent bioactive targeting of the homologous TCM and physico-magnetic targeting of tumor tissues with an external magnetic field. Impressive chemodynamic therapeutic effects on SMCC-7721 tumors are demonstrated through the catalysis of endogenous hydrogen peroxide and depletion of GSH to generate high levels of ROS. Dual-targeting FM@TCM NPs inhibit SMCC-7721 tumor growth (∼90.9%) in vivo without any biotoxicity. This nanotheranostic agent has great potential for use in MRI-guided CDT.

Compartmentalized Nano-MOFs as Co-delivery Systems for Enhanced Antitumor Therapy.

Therapeutic bioactive macromolecules hold great promise in cancer therapy, but challenges such as low encapsulation efficiency and susceptibility to inactivation during the targeted co-delivery hinder their widespread applications. Compartmentalized nano-metal-organic frameworks (nMOFs) can easily load macromolecules in the innermost layer, protect them from the outside environment, and selectively release them in the target location after stimulation, showing great potential in the co-delivery of biomacromolecules. Herein, the rationally designed (GOx + CAT)/ZIF-8@BSATPZ/ZIF-8 (named GCZ@BTZ) nMOFs with compartmentalized structures are employed to deliver cascaded enzymes and the chemotherapeutic drug tirapazamine (TPZ)-conjugated bovine serum albumin (BSATPZ). Benefiting from the compartmentalized structure and protective shell, the GCZ@BTZ system is stable during blood circulation and preferentially accumulates in the tumor. Furthermore, in response to the acidic tumor environment, GCZ@BTZ effectively released the loading enzymes and BSATPZ. Along with the tumor starvation caused by depletion of glucose, cascaded reactions could also contribute to the enhancement of tumor hypoxia, which further activated BSATPZ-based chemotherapy. Notably, in the mouse tumor models, GCZ@BTZ treatment significantly inhibits tumor survival and metastasis. Such a compartmentalized nMOF delivery system presents a promising avenue for the efficient delivery of bioactive macromolecules.

Fe/MOF based platform for NIR laser induced efficient PDT/PTT of cancer.

Introduction: Photodynamic therapy (PDT) and photothermal therapy (PTT) are widely used in the treatment of tumors. However, their application in the treatment of clinical tumors is limited by the complexity and irreversible hypoxia environment generated by tumor tissues. To overcome this limitation, a nanoparticle composed of indocyanine green (ICG) and Fe-MOF-5 was developed. Methods: We prepared F-I@FM5 and measured its morphology, particle size, and stability. Its enzyme like ability and optical effect was verified. Then we used MTT, staining and flow cytometry to evaluated the anti-tumor effect on EMT-6 cells in vitro. Finally, the anti-tumor effect in vivo has been studied on EMT-6 tumor bearing mice. Results: For the composite nanoparticle, we confirmed that Fe-MOF-5 has the best nanozyme activity. In addition, it has excellent photothermal conversion efficiency and generates reactive oxygen species (ROS) under near-infrared light irradiation (808 nm). The composite nanoparticle showed good tumor inhibition effect in vitro and in vivo, which was superior to the free ICG or Fe-MOF-5 alone. Besides, there was no obvious cytotoxicity in major organs within the effective therapeutic concentration. Discussion: Fe-MOF-5 has the function of simulating catalase, which can promote the decomposition of excessive H2O2 in the tumor microenvironment and produce oxygen to improve the hypoxic environment. The improvement of tumor hypoxia can enhance the efficacy of PDT and PTT. This research not only provides an efficient and stable anti-tumor nano platform, but also has broad application prospects in the field of tumor therapy, and provides a new idea for the application of MOF as an important carrier material in the field of photodynamic therapy.

Rapid controllable synthesis of branched Au superparticles: formation mechanism of toggling the growth mode and their applications in optical broadband absorption.

We develop a tunable, ultrafast (5 seconds), and mass-producible seed-mediated synthesis method to prepare branched Au superparticles consisting of multiple small Au island-like nanoparticles by a wet chemical route. We reveal and confirm the toggling formation mechanism of Au superparticles between the Frank-van der Merwe (FM) growth mode and the Volmer-Weber (VW) growth mode. The key factor of this special structure is the frequent toggling between the FM (layer by layer) growth mode and the VW (island) growth mode induced by 3-aminophenol, which is continuously absorbed on the surface of newborn Au nanoparticles, leading to a relatively high surface energy during the overall synthesis process, thus achieving an island on island growth. Such Au superparticles demonstrate broadband absorption from visible to near-infrared regions due to their multiple plasmonic coupling and hence they have important applications in sensors, photothermal conversion and therapy, etc. We also exhibit the excellent properties of Au superparticles with different morphologies, such as NIR-II photothermal conversion and therapy and SERS detection. The photothermal conversion efficiency under 1064 nm laser irradiation was calculated to be as high as 62.6% and they exhibit robust photothermal therapy efficiency. This work provides insight into the growth mechanism of plasmonic superparticles and develops a broadband absorption material for highly efficient optical applications.

Gold nanobipyramid@copper sulfide nanotheranostics for image-guided NIR-II photo/chemodynamic cancer therapy with enhanced immune response.

Photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) can cause cancer cell death through an immunogenic process. However, the study of second near-infrared window (NIR-II)-triggered PTT and PDT combined with CDT to induce an immune response has not been recently reported. Here, we integrated gold nanobipyramids and copper sulfide in a core/shell architecture (AuNBP@CuS). The material displays both photodynamic and photothermal properties under irradiation with a NIR-II laser. The released Cu2+ from CuS under an acidic tumor microenvironment can be converted to Cu+ by glutathione following a Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals in the tumor region. Both in vitro and in vivo results demonstrated that such multifunctional nanoplatforms could achieve enhanced efficiency for image-guided tumor suppression based on the NIR-II photo/chemodynamic therapy. We found that damage-associated molecular pattern molecules such as adenosine triphosphate, pre-apoptotic calreticulin, and high mobility group box-1 in dying cells induced by the NIR-II photo/chemodynamic therapy could simultaneously trigger adaptive immune responses. This is the first report revealing that NIR-II photo/chemodynamic therapy based on AuNBP@CuS had promising performance on tumor suppressor with an effective immunogenic cell death process. STATEMENT OF SIGNIFICANCE: 1. AuNBP@CuS displays both NIR-II photodynamic and photothermal properties. 2. Cu+ following a Fenton-like reaction to generate highly toxic hydroxyl radicals. 3. The NIR-II photo/chemodynamic therapy can trigger adaptive immune responses. 4. Such multifunctional nanoplatforms could achieve enhanced efficiency for tumor suppression.

In situ growing 3D-Cu coating to improve the reversibility and reaction kinetics of Zn metal anodes.

The zinc metal anode is the most promising metal anode material in aqueous battery systems due to its low cost and high theoretical capacity. However, it still undergoes irreversible reactions such as premature failure of the dendrites/dead Zn during Zn stripping/plating, resulting in the inferior cycling stability of the Zn-based full cell. Here, we demonstrate a facile 3D-Cu alloy coating to improve Zn reversibility by providing spatial voids to accommodate the plated Zn to form dendrite-free morphology. Combining the larger 3D surface and the alloying-dealloying process, the Zn anode reactions exhibit enhanced reaction kinetics to meet large operating current densities. The 3D-Cu-coated Zn anode can deliver improved cycling stability for 350 h under a large areal capacity of 3 mAh cm-2. It also enables MnO2-Zn at the full cell level to achieve a specific capacity of 205 mAh g-1 and longer cycling for 350 cycles with 87.4% retention of the initial capacity. This research provides a new pathway to achieve high reversible Zn metal chemistry.

Atom Absorption Energy Directed Symmetry-Breaking Synthesis of Au-Ag Hierarchical Nanostructures and Their Efficient Photothermal Conversion.

Asymmetric plasmonic hierarchical nanostructures (HNs) are of great significance in optics, catalysis, and sensors, but the complex growth kinetics and lack of fine structure design limit their practical applications. Herein, a new atom absorption energy strategy is developed to achieve a series of Au-Ag HNs with the continuously tuned contact area in Janus and Ag island number/size on Au seeds. Different from the traditional passive growth mode, this strategy endows seed with a hand to capture the hetero atoms in a proactive manner, which is beyond the size, shape, and assembles of Au seed. Density functional theory reveals ththe adsorption of PDDA on Au surface leads to lower formation energy of Au-Ag bonds (-3.96 eV) than FSDNA modified Au surface (-2.44 eV). The competitive adsorption of two ligands on Au seed is the decisive factor for the formation of diverse Au-Ag HNs. In particular, the Au-Ag2 HNs exhibit outstanding photothermal conversion capability in the near-infrared window, and in vivo experiments verify them as superior photothermal therapy agents. This work highlights the importance of the atom absorption energy strategy in unlocking the diversity of HNs and may push the synthesis and application of superstructures to a higher level.

All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 µg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

Rational design of non-toxic GOx-based biocatalytic nanoreactor for multimodal synergistic therapy and tumor metastasis suppression.

Rationale: Glucose oxidase (GOx)-based biocatalytic nanoreactors can cut off the energy supply of tumors for starvation therapy and deoxygenation-activated chemotherapy. However, these nanoreactors, including mesoporous silica, calcium phosphate, metal-organic framework, or polymer nanocarriers, cannot completely block the reaction of GOx with glucose in the blood, inducing systemic toxicity from hydrogen peroxide (H2O2) and anoxia. The low enzyme loading capacity can reduce systemic toxicity but limits its therapeutic effect. Here, we describe a real 'ON/OFF' intelligent nanoreactor with a core-shell structure (GOx + tirazapamine (TPZ))/ZIF-8@ZIF-8 modified with the red cell membrane (GTZ@Z-RBM) for cargo delivery. Methods: GTZ@Z-RBM nanoparticles (NPs) were prepared by the co-precipitation and epitaxial growth process under mild conditions. The core-shell structure loaded with GOx and TPZ was characterized for hydrate particle size and surface charge. The GTZ@Z-RBM NPs morphology, drug, and GOx loading/releasing abilities, system toxicity, multimodal synergistic therapy, and tumor metastasis suppression were investigated. The in vitro and in vivo outcomes of GTZ@Z-RBM NPs were assessed in 4T1 breast cancer cells. Results: GTZ@Z-RBM NPs could spatially isolate the enzyme from glucose in a physiological environment, reducing systemic toxicity. The fabricated nanoreactor with high enzyme loading capacity and good biocompatibility could deliver GOx and TPZ to the tumors, thereby exhausting glucose, generating H2O2, and aggravating hypoxic microenvironment for starvation therapy, DNA damage, and deoxygenation-activated chemotherapy. Significantly, the synergistic therapy effectively suppressed the breast cancer metastasis in mice and prolonged life without systemic toxicity. The in vitro and in vivo results provided evidence that our biomimetic nanoreactor had a powerful synergistic cascade effect in treating breast cancer. Conclusion: GTZ@Z-RBM NPs can be used as an 'ON/OFF' intelligent nanoreactor to deliver GOx and TPZ for multimodal synergistic therapy and tumor metastasis suppression.

Rapid synthesis of monodispersed Au-Ag alloy nanosponges using selective laser melting and dealloying for sensitive near-infrared surface-enhanced Raman scattering.

We developed a rapid synthesis method for monodispersed Au-Ag alloy nanosponges (NSs) with high density of 'hotspots' for near-infrared surface enhanced Raman scattering (NIR-SERS) by a selective laser-irradiation melting and chemical dealloying process. Au@Ag core-shell nanocubes were firstin situconverted into solid alloyed Au-Ag nanospheres by a rapid laser irradiation igniting quick fusion and quenching process within two minutes. The alloyed Au-Ag nanospheres transformed into Au-Ag alloy NSs after treated by a chemical dealloying process. Different from traditional thermal annealing, it thus can effectively avoid the heat fusion between nanoparticles, and maintain the alloyed Au-Ag nanospheres and NSs in high monodispersity. Importantly, due to the strong plasmonic coupling in nanopores (pore size less than 10 nm), the obtained Au-Ag alloy NSs show a broad and intense localized surface plasmon resonances absorption ranging from visible to near-Infrared region (500-1200 nm). The accessibly open structures for absorbing targets and high-density of 'NIR-hotspots' endow the Au-Ag alloy NSs substrate with superior sensitivity in NIR-SERS detection of 4-aminothiophenol with an enhancement factor of ∼107. This work not only provides a simple pathway for rapid preparation of NIR-SERS substrate for biosensing, but also might open up a new horizon for fabricating spongy nanostructures with other elements.

Pre- and post-irradiation mild hyperthermia enabled by NIR-II for sensitizing radiotherapy.

The clinical application of cancer radiotherapy is critically impeded by hypoxia-induced radioresistance, insufficient DNA damage, and multiple DNA repair mechanisms. Herein we demonstrate a dual-hyperthermia strategy to potentiate radiotherapy by relieving tumor hypoxia and preventing irradiation-induced DNA damage repair. The tumor hyperthermia temperature was well-controlled by a near infrared laser with minimal side effects using PEGylated nanobipyramids (PNBys) as the photo-transducer. PNBys have narrow longitudinal localized surface plasmon resonance peak in NIR-II window with a high extinction coefficient (2.0 × 1011 M-1 cm-1) and an excellent photothermal conversion efficiency (44.2%). PNBys-induced mild hyperthermia (MHt) prior to radiotherapy enables vessel dilation, blood perfusion, and hypoxia relief, resulting in an increased susceptibility of tumor cells response to radiotherapy. On the other hand, MHt after radiotherapy inhibits the repair of DNA damage generated by irradiation. The PNBys exert hierarchically superior antitumor effects by the combination of MHt pre- and post-radiotherapy in murine mammary tumor EMT-6 model. Consequently, different from the simple combination of RT and MHt, the coupling of pre- and post-MHt with RT by PNBys open intriguing avenues towards new promising antitumor efficacy.

Dynamically Tunable Plasmonic Band for Reversible Colorimetric Sensors and Surface-Enhanced Raman Scattering Effect with Good Sensitivity and Stability.

A colorimetric sensor based on plasmonic nanoparticles (NPs) is a promising and convenient detection tool, but its reproducibility and adjustability remain a challenge because the NPs are mainly random and uncontrollable. Herein, a colorimetric sensor with good reversibility and reproducibility was prepared by embedding the two-dimensional (2D) Au NP arrays on the surface of the polyacrylamide hydrogel film to form 2D Au NP arrays attached a hydrogel composite. For this composite, with the change of the interspacing distance of Au NPs driven by the swelling-shrinking behavior of the hydrogel carrier, the diffraction peaks faded away and plasmonic coupling peaks appeared, accompanied by a series of obvious color changes (iridescence ↔ violet ↔ golden yellow ↔ red), which can be correlated to the applied water content. Importantly, the composite had good reproducibility as a result of a highly ordered array structure. Additionally, this colorimetric sensor with a dynamically tunable plasmonic band can be used as a high-quality surface-enhanced Raman scattering (SERS) substrate because the gap distance of the Au NPs can be uniformly controlled. We demonstrated that, as the active gap distance decreased, the SERS signals can be significantly intensified. When the water content reached 40%, this SERS substrate exhibited high sensitivity (10-10 M for 4-aminothiophenol and 10-9 M for thiram) and good reproducibility (relative standard deviation of <20%) using the excitation laser of 785 nm because of the small gap between two adjacent Au NPs and the highly ordered periodic structure. Such 2D Au NP arrays attached to a hydrogel composite could be a new strategy to obtain a high-quality colorimetric sensor and dynamic SERS substrate.

Nanoplatforms with Remarkably Enhanced Absorption in the Second Biological Window for Effective Tumor Thermoradiotherapy.

Thermoradiotherapy acts as an important antitumor modality because heating can increase the blood flow and improve the oxygen level in tumor, thus remission of hypoxia-associated resistance for radiotherapy (RT). However, most agents for thermoradiotherapy are used either in the first near-infrared biological window or low photothermal conversion efficiency. Here, a facile method to prepare CuxS/Au nanocomposites via reduction methods from CuxS templates in mild synthetic conditions (i.e., aqueous solution and room temperature) is presented. After the growth of Au nanoparticles, the CuxS/Au nanocomposites have greater benefits for photothermal efficiency than that of CuxS nanoparticles due to the enhanced absorbance in the second near-infrared window. Moreover, biocompatibility and stability of these nanocomposites are greatly improved by lipoic acid poly(ethylene glycol). After the tumors were irradiated with a 1064 nm laser, their oxygenation status is subsequently improved, and the combination of photothermal therapy and RT achieves remarkable synergistic therapeutic effects. This work provides a novel idea to design a new-generation nanomedicine for tumor thermoradiotherapy.

Au@Prussian Blue Hybrid Nanomaterial Synergy with a Chemotherapeutic Drug for Tumor Diagnosis and Chemodynamic Therapy.

Recently, the chemodynamic therapy (CDT) has been widely reported and applied to tumor therapy. However, only low level hydroxyl radicals (•OH) generated by the endogenous hydrogen peroxide alone are insufficient to kill the cancer cells. To overcome the insufficient therapeutic effect, this study reports a novel CDT based on Fenton catalyst Au@Prussian blue nanocubes (Au@PB NCs), subsequently encapsulated with doxorubicin (Dox). The in vitro and in vivo results indicate that the Dox-Au@PB NCs can take synergistic effects on tumor suppressor by CDT. In addition, Au@PB NCs possess high X-ray computed tomography contrast enhanced efficiency about ∼27.13 HU·mL·mg-1. This study highlights a great potential of the Dox-Au@PB NCs for tumor diagnosis and CDT.

Synergistic Effect of Retinoic Acid Polymeric Micelles and Prodrug for the Pharmacodynamic Evaluation of Tumor Suppression.

All-trans retinoic acid (ATRA) is an effective agent that induces differentiation, inhibits cell proliferation, and acts as an anticancer agent. ATRA was successfully conjugated with Pluronic F127 via esterification to enhance its anticancer effects. Pluronic-ATRA showed high cytotoxicity and inhibitory concentrations (IC50) 50% lower than those of ATRA in various breast cancer cell lines (4T1:31.16-8.57 µg/mL; EMT6: 50.48-7.08 µg/mL; MDA-MB-231:37.58-8.99 µg/mL; BT474:25.27-9.09 µg/mL). In combination with chemotherapy, Pluronic-ATRA synergistically enhanced the cytotoxic effects of cisplatin (CDDP). Pluronic-ATRA combined with CDDP effectively suppressed breast tumor growth in vivo. The results of this study demonstrate the potential of Pluronic-ATRA as an anticancer agent that can be used in combination therapy against solid tumors.

ROS-sensitive biomimetic nanocarriers modulate tumor hypoxia for synergistic photodynamic chemotherapy.

Tumor hypoxia, which is indispensable to tumor propagation and therapy resistance, has been one of the most important factors influencing clinical outcomes. To modulate the hypoxia microenvironment, we herein developed reactive oxygen species (ROS)-sensitive arylboronic ester-based biomimetic nanocarriers co-encapsulated with a photosensitizer chlorin e6 (Ce6) and a hypoxia-activated prodrug tirapazamine (TPZp) for tumor-specific release and synergistic photodynamic chemotherapy. In order to bypass macrophage uptake and improve tumor penetration, the nanocarriers were further modified with the red blood cell membrane and iRGD peptide (denoted as NPs@i-RBMCe6+TPZp). After administration, NPs@i-RBMCe6+TPZp exhibited prolonged blood circulation, selective tumor accumulation and excellent penetration into the tumor interior. Upon light irradiation, ROS were generated by Ce6 for photodynamic therapy (PDT), which subsequently caused dissociation of the ROS-responsive nanocarriers. An enhanced therapeutic effect was further achieved through the activation of TPZp in the aggravated local hypoxia microenvironment. The synergistic cancer therapy based on NPs@i-RBMCe6+TPZp significantly suppressed tumor growth with negligible side effects. The biomimetic nanocarriers have great potential to overcome hypoxia-limited PDT, and significantly improve the anticancer efficacy by synergistic tumor-targeted PDT and hypoxia-activated chemotherapy.

Au nanoparticles with enzyme-mimicking activity-ornamented ZIF-8 for highly efficient photodynamic therapy.

The tumor hypoxic microenvironment (THME) has a profound impact on tumor progression, and modulation of the THME has become an essential strategy to promote photodynamic therapy (PDT). Here, an oxygen self-supplied nanodelivery system that is based on nanometal-organic frameworks (nMOFs) with embedded AuNPs (Au@ZIF-8) on the nMOF surface as a catalase (CAT)-like nanozyme and encapsulating Ce6 inside as a photosensitizer was found to mitigate tumor hypoxia and reinforce PDT. As soon as Au@ZIF-8 reaches the tumor site, the AuNP nanozyme can catalyze excessive H2O2 to produce O2 to alleviate tumor hypoxia, promoting the production of 1O2 with strong toxicity toward tumor cells under irradiation. Our study demonstrates that nMOFs embellished with a nanozyme have great potential for overcoming the THME for cancer therapeutics, which provides a facile strategy for accurate bioimaging and cancer therapy in vivo.