Cobalt protoporphyrin-induced nano-self-assembly for CT imaging,magnetic-guidance,and antioxidative protection of stem cells in pulmonary fibrosis treatment

Mesenchymal stem cells(MSCs)transplantation is a promising approach for pulmonary fibrosis(PF),however it is impeded by several persistent challenges,including the lack of long-term tracking,low retention,and poor survival of MSCs,as well as the low labeling efficiency of nanoprobes.Herein,a cobalt protoporphyrin IX(CoPP)aggregation-induced strategy is applied to develop a multifunctional nano-self-assembly(ASCP)by combining gold nanoparticle(AuNPs),superparamagnetic iron oxide nanoparticles(SPIONs),and CoPP through a facile solvent evaporation-driven approach.Since no additional carrier materials are employed during the synthesis,high loading efficiency of active ingredients and excellent biocompatibility are achieved.Additionally,facile modification of the ASCPs with bicyclo[6.1.0]nonyne(BCN)groups(named as ASCP-BCN)enables them to effectively label MSCs through bioorthogonal chemistry.The obtained ASCP-BCN could not only help to track MSCs with AuNP-based computed tomography(CT)imaging,but also achieve an SPIONs-assisted magnetic field based improvement in the MSCs retention in lungs as well as promoted the survival of MSCs via the sustained release of CoPP.The in vivo results demonstrated that the labeled MSCs improved the lung functions and alle-viated the fibrosis symptoms in a bleomycin–induced PF mouse model.Collectively,a novel ASCP-BCN multi-functional nanoagent was developed to bioorthogonally-label MSCs with a high efficiency,presenting a promising potential in the high-efficient MSC therapy for PF.

Recent deveolpment of multifunctional responsive gas-releasing nanoplatforms for tumor therapeutic application

Gas therapy(GT)exhibits great potential for clinical application due to its high therapeutic efficiency,low systemic side effects,and biosafety,thereinto,a multifunctional nanoplatform is generally needed for controllable gas release and precise delivery to tumor tissue.In this review,the recent development of multifunctional nanoplatforms for efficient tumor delivery of stimuliresponsive gas-releasing molecules(GRMs),which could be triggered by either exogenous physical or endogenous tumor microenvironment(TME)is summarized.The reported therapeutic gas molecules,including oxygen(O_(2)),hydrogen sulfide(H_(2)S),nitric oxide(NO),hydrogen(H_(2)),and carbon monoxide(CO),etc.,could directly influence or change the pathological status.Additionally,abundant nanocarriers have been employed for gas delivery into cancer region,such as mesoporous silica nanoparticles(MSNs),metal-organic frameworks(MOFs),two-dimensional(2D)nanomaterials,and liposomes,as well as nonnanocarriers including inorganic and organic nanoparticles.In the end,the outlooks of current challenges of GT and GRMs delivery nanoplatforms as well as the prospects of future clinical applications are proposed.

In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis

Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outcome owing to hard deep reaching to hypoxic region,and the occurrence of metastasis due to hypoxia.Inspired by engineered niches,a novel functional chitosan polymer(CS-FTP)is synthesized for construction of a hydrogel-based bio-niche(CS-FTP-gel)in aiming at remodeling tumor hypoxic microenvironment.The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor,in which a HAP(i.e.,AQ4N)could be physically encapsulated,resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy.Furthermore,Pazopanib(PAZ)conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation,eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model.This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.

Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme

The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology.Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression,metastasis,and poor outcome of cancer,while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization.Thus,the mutually-beneficial interplay between pathogens and tumors,named“pathogentumor symbionts”,is probably a potential therapeutic site for tumor treatment.Herein,we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens,F.nucleatum,to break the symbiont and synergize to kill colorectal cancer(CRC)cells.This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme(BSA-Cu SAN)which was inspired by the structures of native enzymes that are based on protein,with metal elements as the active center.BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species(ROS)and depleting GSH.The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F.nucleatum in situ to destroy pathogentumor symbionts.As a result,ROS resistance of CRC through elevated autophagy mediated by F.nucleatum was relieved,contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN.Particularly,BSA-Cu SAN experiences renal clearance,avoiding long-term systemic toxicity.This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.

Construction of smart inorganic nanoparticle-based ultrasound contrast agents and their biomedical applications

Ultrasound(US) imaging in combination with US contrast agents(UCAs) is a powerful tool in the modern biomedical field because of its high spatial resolution, easy access to patients and minimum invasiveness.The microbubble-based UCAs have been widely used in clinical diagnosis; however, they are only limited to the blood pool imaging and not applicable to the tissue-penetrated imaging due to their large particle size and structural instability. Inorganic nanoparticles(NPs), such as silica,gold and Fe x O y, featured with both satisfactory echogenic properties and structural stability have the potential to be used as a new generation of UCAs. In this review, we present the most recent progresses in the tailored construction of inorganic UCAs and their biomedical applications in the US imaging-involved fields. Firstly, the typical inorganic NPs with different structures including solid, hollow and multiple-layer forms will be comprehensively introduced in terms of their structure design,physicochemical property, US imaging mechanism and diverse applications; secondly, the recent progress in exploring the gas-generating inorganic NP system for US imaging purpose will be reviewed, and these intelligent UCAs are multifunctional for simultaneous US imaging and disease therapy; thirdly, several nanocomposite platforms newly constructed by combining inorganic UCAs with other functional components will be presented anddiscussed. These multifunctional NPs are capable of further enhancing the imaging resolution by providing more comprehensive anatomical information simultaneously.Last but not the least, the design criteria for developing promising UCAs to satisfy both clinical demands and optimized US imaging capability will be discussed and summarized in this review.

H2O2-responsive theranostic nanomedicine

The fast progress of stimuli-responsive theranostic nanomedicine can achieve the specific and highperformance diagnosis and therapy of various diseases.Especially,H2O2-responsive theranostic nanomedicine is recently emerging as a new stimuli-responsive modality showing the great potential for the theranostic of diseases with overexpressed H2O2 because H2O2 is associated with several kinds of human diseases as the most stable and abundant reactive oxygen species.This review summarizes and discusses the very-recent developments of H2O2-responsive theranostic nanoplatforms for versatile biomedical applications,including diagnostic imaging,attenuating tumor hypoxia,enhancing the therapeutic efficiency of photodynamic therapy/radiation therapy/chemotherapy and theranostic of inflammation/diabetic.The facing challenges and future developments of H2O2-responisve theranostics are also briefly discussed to further promote the clinical translation of this new responsive theranostic modality.It is highly believed that H2O2-responsive theranostic nanomedicine will be extensively developed a new specific and efficient theranostic modality to benefit the personalized biomedicine in the near future.

Design strategy of optical probes for tumor hypoxia imaging

Clinical manifestations of tumors indicate that malignant phenotypes developing in the hypoxic microenvironment lead to resistance to cancer treatment, rendering chemotherapy, radiotherapy, and photodynamic therapy less sensitive and effective in patients with tumor. Visualizing the oxygen level in the tumor environment has garnered much attention due to its implications in precision tumor therapy. Following the rapid development of biomaterials in nanotechnology, various nanomaterials have been designed to visualize the oxygen levels in tumors. Here, we review recent research on detecting oxygen levels in solid tumors for tumor hypoxia imaging. To monitor the hypoxic level of tumors, two main strategies were investigated: directly detecting oxygen levels in tumors and monitoring the hypoxia-assisted reduced microenvironment. We believe that hypoxia as a tumor-specific microenvironment can be a breakthrough in the clinical treatment of tumors.

Sodium carbonate-assisted synthesis of hierarchically porous single-crystalline nanosized zeolites

Hierarchically porous single-crystalline nanosized zeolites as heterogeneous catalysts show great potential in fine chemistry because they offer more rich hierarchically porous channels for the mass transfer and molecular diffusion. However, the synthesis of hierarchically porous nanosized zeolites generally requires the assistance of templates acting as the mesoporogens, which limits its popularity. Herein,we report a one-pot and template-free synthesis of hierarchically porous single-crystalline nanosized zeolite beta only by introducing sodium carbonate in precursor solution. The resulted sample features the extraordinary properties, including the uniform nanocrystal(200–300 nm), high pore volume(0.65 cm^3g^(-1)) and the hierarchical pore-size distribution(e.g. 2–8 and 90–150 nm). After slicing processing, it is interestingly found that a large number of interconnected mesopores penetrate throughout whole material, which enables the hierarchically porous nanosized zeolite beta remarkably superior catalytic activity than the conventional zeolite beta in condensation of benzaldehyde with ethanol at room temperature. More importantly, this one-pot sodium carbonate-assisted synthetic strategy is highly versatile, which has also been successfully developed to synthesize hierarchically porous nanosized singlecrystalline zeolites ZSM-5 and TS.