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.

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.

Herein, we report the design and synthesis of a mitochondria‐specific, 808 nm NIR light‐activated photodynamic therapy (PDT) system based on the combination of metal–organic frameworks (MOFs) and upconversion photochemistry with an organelle‐targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd3+‐sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser‐irradiation‐induced overheating effect. Furthermore, mitochondria‐targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.

Developing simple and general approaches for the synthesis of nanometer-sized DNAm aterials with specific morphologies and functionalities is important for various applications.H erein, an ovel approachf or the synthesis of anew set of DNA-based nanoarchitectures through coordination-driven self-assembly of Fe II ions and DNAm olecules is reported. By fine-tuning the assembly,F e-DNAn anospheres of precise sizes and controlled compositions can be produced. The hybrid nanoparticles can be tailored for delivery of functional DNAt oc ells in vitro and in vivo with enhanced biological function. This highlights the potential of metal ion coordination as at ool for directing the assembly of DNA architectures,w hichc onceptualizes an ew pathway to expand the repertoire of DNA-based nanomaterials.This methodology will advance both the fields of DNAn anobiotechnology and metal-ligand coordination chemistry.The past decade has witnessed worldwide interest in the construction of DNA-based nanomaterials due to their numerous applications ranging from biomedicine to biotechnology. [1][2][3][4][5] Because DNAi su nable to penetrate cell membranes,integration of DNAwith functional nanocarriers (e.g. cationic polymeric and liposomal systems) to promote the delivery is of interest. [2] Recently,D NA-nanotechnologyenabled nanomaterials (e.g., DNAo rigami and spherical nucleic acids), which enable delicate structure tailoring and good biocompatibility, [3][4][5] have shown great potential to transport therapeutic nucleic acids or molecular cargos into cells for various applications. [1] However,t he current approaches are often limited by sophisticated materials synthesis and formulation processes.S trategies aiming at reducing complexity in the synthesis process and increasing scalability and functionality remain ac entral theme in the field of DNA-based nanomaterials.Coordination-driven self-assembly has proven to be one of the most attractive strategies in supramolecular chemistry for the bottom-up construction of functional molecular architectures and materials. [6] Examples of such ensembles range from coordination polymers (CPs), [7] metal-organic frameworks (MOFs), [8] to supramolecular polymer gels. [9] The integration of organic and inorganic components into these materials at the molecular level could increase their structural complexity and endow them with advanced functionalities and broader applications. [6][7][8][9] In particular, nanoscale CPs are rapidly emerging as one of the most active research fields among the chemistry and materials communities,a sd emonstrated by versatile applications for catalysis,o ptical and magnetic materials,a nd nanomedicine. [7] To date,m ost of such systems are built from small organic molecules and metal ions. [7a-f] Most recently,s mall biomolecules (e.g,t annic acid and dipeptides) have been explored for the assembly of functional CP nanoparticles (NPs) for potential bioimaging and drug delivery applications. [7g-i] Despite successful attempts,t oo ur knowledge,c ontrolled syn...

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.

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.

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.

Despite the potential of nanodevices for intelligent drug delivery, it remains challenging to develop controllable therapeutic devices with high spatial-temporal selectivity. Here, we report a DNA nanodevice that can achieve tumor recognition and treatment with improved spatiotemporal precision under the regulation of orthogonal near-infrared (NIR) light. The nanodevice is built by combining an ultraviolet (UV) light–activatable aptamer module and a photosensitizer (PS) with up-conversion nanoparticle (UCNP) that enables the operation of the nanodevice with deep tissue–penetrable NIR light. The UCNPs can convert two distinct NIR excitations into orthogonal UV and green emissions for programmable photoactivation of the aptamer modules and PSs, respectively, allowing spatiotemporally controlled target recognition and photodynamic antitumor effect. Furthermore, when combined with immune checkpoint blockade therapy, the nanodevice results in regression of untreated distant tumors. This work provides a new approach for regulation of diagnostic and therapeutic activity at the right time and place.