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Metal-organic frameworks (MOFs) have shown great potential as nanophotosensitizers (nPSs) for photodynamic therapy (PDT). The use of such MOFs in PDT, however, is limited by the shallow depth of tissue penetration of short-wavelength light and the oxygen-dependent mechanism that renders it inadequate for hypoxic tumors. Here, to combat such limitations, we rationally designed core-shell upconversion nanoparticle@porphyrinic MOFs (UCSs) for combinational therapy against hypoxic tumors. The UCSs were synthesized in high yield through the conditional surface engineering of UCNPs and subsequent seed-mediated growth strategy. The heterostructure allows efficient energy transfer from the UCNP core to the MOF shell, which enables the near-infrared (NIR) light-triggered production of cytotoxic reactive oxygen species. A hypoxia-activated prodrug tirapazamine (TPZ) was encapsulated in nanopores of the MOF shell of the heterostructures to yield the final construct TPZ/UCSs. We demonstrated that TPZ/UCSs represent a promising system for achieving improved cancer treatment in vitro and in vivo via the combination of NIR light-induced PDT and hypoxia-activated chemotherapy. Furthermore, the integration of the nanoplatform with antiprogrammed death-ligand 1 (α-PD-L1) treatment promotes the abscopal effect to completely inhibit the growth of untreated distant tumors by generating specific tumor infiltration of cytotoxic T cells. Collectively, this work highlights a robust nanoplatform for combining NIR light-triggered PDT and hypoxia-activated chemotherapy with immunotherapy to combat the current limitations of tumor treatment.

Despite a growing interest in DNA nanomaterials, their simple synthesis remains a challenge. A simple and general strategy for constructing DNA-based nanomaterials by metal ion coordination is reported. The metal-DNA nanoparticles(NPs) could be synthesized with DNA molecules of diverse sequence and various metal ions of intrinsic property, resulting in multifunctional NPs with the combined advantages of both inorganic and DNA building blocks. It is demonstrated that the hybrid metal-DNA NPs could be engineered for magnetic resonance and luminescence imaging, encapsulation of multifarious nucleic acids with controlled ratio, and co-assembly with small drug molecules. Furthermore, because these metal-DNA NPs exhibited enhanced cellular uptake compared to free synthetic DNA, they hold potential for applications in diagnostics and therapeutics.

superstructures has enormous potential in material sciences and engineering. Despite the potential, controlled assembly of different kinds of NPs into spatially addressable hybrid configurations still remains a formidable challenge. Herein, we report a simple and universal strategy for DNA-mediated assembly of CdTe quantum dots (QDs) and lanthanide-doped upconversion nanoparticles (UCNPs). Such DNA-QD/UCNPs heterostructures not only maintains both fluorescent properties of QDs and upconversion luminescence behaviors of UCNPs, but also offers a polyvalent DNA surface, allowing for targeted dual-modality imaging of cancer cells using an aptamer. The hetero-assembly mediated by the DNA − inorganic interfacial interaction may provide a scalable way to fabricate hybrid superstructures of both theoretical and practical interests.

Designer DNA nanodevices have attracted extensive interest for detection of specific targets in living cells. However, it still remains a great challenge to construct DNA sensing devices that can be activated at desired time with a remotely applied stimulus. Here we report a rationally designed, synthetic DNA nanodevice that can detect ATP in living cells in an upconversion luminescence-activatable manner. The nanodevice consists of a UV light-activatable aptamer probe and lanthanide-doped upconversion nanoparticles which acts as the nanotransducers to operate the device in response to NIR light. We demonstrate that the nanodevice not only enables efficient cellular delivery of the aptamer probe into live cells, but also allows the temporal control over its fluorescent sensing activity for ATP by NIR light irradiation in vitro and in vivo. Ultimately, with the availability of diverse aptamers selected in vitro, the DNA nanodevice platform will allow NIR-triggered sensing of various targets as well as modulation of biological functions in living systems.

Here we report, for the first time, the growth of single-crystalline mesoporous MOFs with well-controlled orientation on the surface of gold nanorods. Importantly, it showed that trace amounts of water could induce the formation of MOFs of different phases and shapes, which was critical for the synthesis of such mesoporous heterostructures.

Creating nanoparticle dimers has attracted extensive interest. However, it still remains a great challenge to synthesize heterodimers with asymmetric compositions and synergistically enhanced functions. In this work, we report the synthesis of high quality heterodimers composed of porphyrinic nanoscale metal-organic frameworks (nMOF) and lanthanide-doped upconversion nanoparticles (UCNPs). Due to the dual optical properties inherited from individual nanoparticles and their interactions, absorption of low energy photons by the UCNPs is followed by energy transfer to the nMOFs, which then undergo activation of porphyrins to generate singlet oxygen. Furthermore, the strategy enables the synthesis of heterodimers with tunable UCNP size and dual NIR light harvesting functionality. We demonstrated that the hybrid architectures represent a promising platform to combine NIR-induced photodynamic therapy and chemotherapy for efficient cancer treatment. We believe that such heterodimers are capable of expanding their potential for applications in solar cells, photocatalysis, and nanomedicine.

There is intense interest in intracellular co-delivery of functional proteins and nucleic acids for diverse biological research and disease treatment. However, efficient co-encapsulation of these two types of biomacromolecules within a single particle remains an outstanding challenge because of their significantly different characteristics and loading competition inside the particles. Here we report an extremely simple approach to produce a hybrid platform for the co-delivery of proteins and nucleic acids into cancer cells. This system was constructed by one-step, coordination-driven self-assembly of proteins and nucleic acids with metal ions, resulting in spherical hybrid architectures with uniform size, ultrahigh loading content and tunable ratios of the two macromolecular components. The platform enables efficient co-delivery of protein and nucleic acid therapeutics into cells and achieves a significant inhibition of tumor growth in vivo. The simple self-assembly strategy offers an effective tool for the co-delivery of macromolecular therapeutics and has great potential for personalized medicine.

Developing simple and general approaches for the synthesis of nanometer-sized DNA materials with specific morphologies and functionalities is important for various applications. Herein, a novel approach for the synthesis of a new set of DNA-based nanoarchitectures through coordination-driven self-assembly of FeII ions and DNA molecules is reported. By fine-tuning the assembly, Fe-DNA nanospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNA to cells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as a tool for directing the assembly of DNA architectures, which conceptualizes a new pathway to expand the repertoire of DNA-based nanomaterials. This methodology will advance both the fields of DNA nanobiotechnology and metal-ligand coordination chemistry.

Surface functionality is an essential component for processing and application of metal-organic frameworks (MOFs). A simple and cost-effective strategy for DNA-mediated surface engineering of zirconium-based nanoscale MOFs (NMOFs) is presented, capable of endowing them with specific molecular recognition properties and thus expanding their potential for applications in nanotechnology and biotechnology. It is shown that efficient immobilization of functional DNA on NMOFs can be achieved via surface coordination chemistry. With this strategy, it is demonstrated that such porphyrin-based NMOFs can be modified with a DNA aptamer for targeting specific cancer cells. Furthermore, the DNA-NMOFs can facilitate the delivery of therapeutic DNA (e.g., CpG) into cells for efficient recognition of endosomal Toll-like receptor 9 and subsequent enhanced immunostimulatory activity in vitro and in vivo. No apparent toxicity is observed with systemic delivery of the DNA-NMOFs in vivo. Overall, these results suggest that the strategy allows for surface functionalization of MOFs with different functional DNAs, extending the use of these materials to diverse applications in biosensor, bioimaging, and nanomedicine.

Extracellular ATP is an emerging target for cancer treatment because it is a key messenger for shaping the tumor microenvironment (TME) and regulating tumor progression. However, it remains a great challenge to design biochemical probes for targeted imaging of extracellular ATP in the TME. A TME-driven DNA nanomachine (Apt-LIP) that permits spatially controlled imaging of ATP in the extracellular milieu of tumors with ultrahigh signal-to-background ratio is reported. It operates in response to the mild acidity in the TME with the pH (low) insertion peptide (pHLIP) module, thus allowing the specific anchoring of the structure-switching signaling aptamer unit to the membrane of tumor cells for "off-on" fluorescence imaging of the extracellular ATP. Apt-LIP allows for acidity driven visualization of different extracellular concentrations of exogenous ATP, as well as the monitoring of endogenous ATP release from cells. Furthermore, it is demonstrated that Apt-LIP represents a promising platform for the specific imaging of the extracellular ATP in both primary and metastatic tumors. Ultimately, since diverse aptamers are obtained through in vitro selection, this design strategy can be further applied for precise detection of various extracellular targets in the TME.

Fluorescent nanoprobes are indispensable tools to monitor and analyze biological species and dynamic biochemical processes in cells and living bodies. Conventional nanoprobes have limitations in obtaining imaging signals with high precision and resolution because of the interference with biological autofluorescence, off-target effects, and lack of spatiotemporal control. As a newly developed paradigm, light-activated nanoprobes, whose imaging and sensing activity can be remotely regulated with light irradiation, show good potential to overcome these limitations. Herein, recent research progress on the design and construction of light-activated nanoprobes to improve bioimaging and sensing performance in complex biological systems is introduced. First, recent innovative strategies and their underlying mechanisms for light-controlled imaging are reviewed, including photoswitchable nanoprobes and phototargeted nanosystems. Subsequently, a short highlight is provided on the development of light-activatable nanoprobes for biosensing, which offer possibilities for the remote control of biorecognition and sensing activity in a precise manner both temporally and spatially. Finally, perspectives and challenges in light-activated nanoprobes are commented.