An orthogonally regulatable DNA nanodevice for spatiotemporally controlled biorecognition and tumor treatment

Abstract

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.

Recent Advances on Rare Earth Upconversion Nanomaterials for Combined Tumor Near-Infrared Photoimmunotherapy

“…Immune checkpoint inhibitors could also corporate with light controlled molecular nanodevices to enhance antitumor efficacy. Di et al designed an orthogonal upconversion nanoplatform, which achieves NIR light deep tissue penetration and specific target recognition of tumors by DNA nanodevices (Di et al, 2020). Therein, DNA is a highly programmable component FIGURE 7 | (A) Scheme of synergistic phototherapy for augmentation of antitumor immunity.…”

“…Immune checkpoint inhibitors could also corporate with light controlled molecular nanodevices to enhance antitumor efficacy. Di et al designed an orthogonal upconversion nanoplatform, which achieves NIR light deep tissue penetration and specific target recognition of tumors by DNA nanodevices (Di et al, 2020 ). Therein, DNA is a highly programmable component that can be used to design molecular nanodevices with specific functions, such as biosensing and imaging (Chen et al, 2015 ), molecular information calculation (Amir et al, 2014 ), and controlled drug delivery and release (Brodin et al, 2015 ; Hu et al, 2019a ).…”

“…Data are means ± SD ( n = 5). Copyright 2020, American Association for the Advancement of Science (Di et al, 2020 ). ** P < 0.01, *** P < 0.001.…”

“…Data are means ± SD (n = 5). Copyright 2020, American Association for the Advancement of Science(Di et al, 2020). **P < 0.01, ***P < 0.001. demonstrated that tumors treated with anti-PD-L1 monoclonal antibody produced a strong antitumor immune response and had a high (T/spleen)_CD8 ratio.…”

A Near‐Infrared Photo‐Switched MicroRNA Amplifier for Precise Photodynamic Therapy of Early‐Stage Cancers

“…[16] Since the first application of UCNPs in NIR-activation mechanism was reported, [17] UCNPs-based activation mechanism has been applied in intracellular imaging of pH and miRNA. [13,18] The NIR-activative DNA cascade reaction has also been designed to amplify the detection signal for spatiotemporally controlled intracelluar mRNA imaging. [19] Here we designed a photo-caged DNA nanocomb for preparation of NIR photo-switched miRNA amplifier to achieve the amplified precise PDT for early stage cancers.…”