Size-Dependent Effect of Indocyanine Green Nanoimaging Agent for Metastatic Lymph Node Detection.

Identification of metastatic lymph nodes is a crucial step in lymph node dissection to prevent further cancer spread and recurrence. However, the current limitations in metastatic lymph node detection often result in extensive resection of normal lymph nodes, leading to serious complications. The clinical application of indocyanine green (ICG) as a tool for lymph node detection is challenging because of its short plasma half-life and rapid light-induced decomposition and clearance. To overcome this limitation, we used polydopamine nanoparticles (PNs) as carriers for ICG and screened for the optimal particle size for detecting metastatic lymph nodes. ICG/PNs with sizes of 80, 160, 300, and 600 nm were synthesized, and their ICG loading efficiency, physical stability, and lymph node distribution were evaluated. The ICG absorbed on the PNs was found to be protected from light degradation, and its retention at the lymph nodes was improved. Notably, the ICG/PNs favored the fluorescence signal at the metastatic lymph nodes compared to the nonmetastatic lymph nodes. Among the tested particle sizes, the 80-nm ICG/PN showed a higher distribution in the metastatic lymph nodes. This study suggests that the 80-nm ICG/PN is a potentially valuable reagent for the detection and diagnosis of lymph node metastasis.

CRISPR/Cas9-Mediated Customizing Strategies for Adoptive T-Cell Therapy.

Clustered regularly interspaced short palindromic repeat-associated protein Cas9 (CRISPR/Cas9) technology is at the forefront of cancer immunotherapy innovation, offering precise and personalized treatment strategies. In this review, we discuss CRISPR/Cas9's ability to precisely edit the genome, its impact on immune checkpoint control, and its application in immune cell engineering, where it surpasses traditional gene editing techniques. Originally inspired by bacterial defense mechanisms, this technology has made great strides in cancer immunotherapy as a mechanism to specifically target the PD-1/PD-L1 pathway in immune checkpoint blockades. In addition, CRISPR/Cas9 plays an important role in cancer treatment by facilitating genetic modifications to enhance the properties of adoptive cell therapy, optimizing the therapeutic potential of this approach. This review provides an overview of the development of CRISPR/Cas9, its important role in immune checkpoint control, applications in immune cell engineering, and the current status of clinical trials. However, safety concerns related to off-target effects and unintended mutations require continued research and caution. Continued advances in CRISPR technology hold the promise of revolutionizing the cancer treatment paradigm, providing personalized and effective therapies for patients with various types of cancer.

Enzyme-responsive macrocyclic metal complexes for biomedical imaging.

Metal chelator-based contrast agents are used as tumor navigators for cancer diagnosis. Although approved metal chelators show excellent contrast performance in magnetic resonance imaging (MRI), large doses are required for cancer diagnoses due to rapid clearance and nonspecific accumulation throughout the body, which can compromise safety. The present study describes an enzyme-responsive metal delivery system, in which enzyme overexpressed in the tumor microenvironment selectively activates the tumor uptake of gadolinium (Gd). Gd was loaded into enzyme-responsive macrocyclam (ErMC) modified with a PEGylated enzyme-cleavable peptide resulting in Gd@ErMC. The PEGylated shell layer protected Gd@ErMC from nonspecific binding in the blood, increasing the half-life of the contrast agent. Specific cleavage of the PEGylated shell layer by the enzyme selectively liberated Gd from Gd@ErMC at the tumor site. Evaluation of the in vivo distribution of Gd@ErMC in tumor-bearing mice by MRI and positron emission tomography (PET) showed that Gd@ErMC had an extended half-life and was highly specific. Histological and serological analysis of Gd@ErMC-treated mice showed that this agent was safe. This novel enzyme-responsive contrast agent delivery system shows promise as specific theranostic agent for MR-guided radiotherapy.

Lysyl oxidase-responsive anchoring nanoparticles for modulation of the tumor immune microenvironment.

In the tumor microenvironment, lysyl oxidase (LOX) is known to play a key role in stabilizing the tumor extracellular matrix. Here, we designed LOX-responsive nanoparticles to interact with the collagen matrix of the tumor microenvironment. Collagen-coated and imiquimod-loaded polydopamine nanoparticles (CPN/IQ) could form crosslinked structures with the collagen matrix via LOX. In vitro, anchoring of CPN/IQ nanoparticles was observed with LOX-secreting CT26 cells, but this was blocked by a LOX inhibitor. In CT26 tumor-bearing mice, co-administration of nanoparticles plus the LOX inhibitor did not significantly alter the antitumor efficacy among nanoparticles. In the absence of the LOX inhibitor, however, a single administration of CPN/IQ could provide sustained responsiveness to near-infrared irradiation and ablation of primary tumors. In the primary tumor microenvironment, CPN/IQ lowered the Treg cell population but increased the cytotoxic CD3+CD8+ T cell population. In splenic dendritic cells, CPN/IQ treatment significantly increased the CD11c+CD86+ and CD11c+CD80+ cell populations. In a CT26 distant tumor-rechallenge model, CPN/IQ treatment increased the cytotoxic CD3+CD8+ T cell population and provided 100% survival of mice until 64 days. This study indicates the feasibility of tumor immune microenvironment modulation using LOX-responsive size-transforming nanoparticles. Although we tested the concept in a CT26 cell-derived tumor model, the concept of LOX-responsive collagen matrix- anchoring nanoparticles may be broadly applied to other tumor tissues with LOX-rich tumor microenvironments.

Immune-Modulating Lipid Nanomaterials for the Delivery of Biopharmaceuticals.

In recent years, with the approval of preventative vaccines for pandemics, lipid nanoparticles have become a prominent RNA delivery vehicle. The lack of long-lasting effects of non-viral vectors is an advantage for infectious disease vaccines. With the introduction of microfluidic processes that facilitate the encapsulation of nucleic acid cargo, lipid nanoparticles are being studied as delivery vehicles for various RNA-based biopharmaceuticals. In particular, using microfluidic chip-based fabrication processes, nucleic acids such as RNA and proteins can be effectively incorporated into lipid nanoparticles and utilized as delivery vehicles for various biopharmaceuticals. Due to the successful development of mRNA therapies, lipid nanoparticles have emerged as a promising approach for the delivery of biopharmaceuticals. Biopharmaceuticals of various types (DNA, mRNA, short RNA, proteins) possess expression mechanisms that are suitable for manufacturing personalized cancer vaccines, while also requiring formulation with lipid nanoparticles. In this review, we describe the basic design of lipid nanoparticles, the types of biopharmaceuticals used as carriers, and the microfluidic processes involved. We then present research cases focusing on lipid-nanoparticle-based immune modulation and discuss the current status of commercially available lipid nanoparticles, as well as future prospects for the development of lipid nanoparticles for immune regulation purposes.

External cold atmospheric plasma-responsive on-site hydrogel for remodeling tumor immune microenvironment.

Although immunotherapy has recently emerged as a promising anti-tumor approach, it remains limited by the immunosuppressive tumor microenvironment. Cold atmospheric plasma irradiation can generate reactive oxygen species and trigger the presentation of tumor-associated antigens. Here, we exploited cold atmospheric plasma for on-site hydrogel application in the tumor environment, aiming to facilitate the sustainable uptake of tumor-associated antigens and nanoadjuvants by dendritic cells. Hyaluronic acid-tyramine conjugate was intratumorally injected as a liquid and formed an on-site hydrogel under irradiation with cold atmospheric plasma. Intratumoral delivery of hyaluronic acid-tyramine conjugate with transforming growth factor ß-blocking nanoadjuvant (TLN) followed by cold atmospheric plasma irradiation yielded a micro-network of TLN-loaded hydrogel (TLN@CHG). In vivo intratumoral injection of TLN@CHG promoted the activation of dendritic cells and more effectively increased the proportion of CD4 T cells and CD8 T cells in the tumor microenvironment, compared to the groups receiving TLN or hydrogel alone. Moreover, in CT26 tumor model mice, cold atmospheric plasma-induced TLN@CHG therapy ablated the primary tumor and provided 100% survival among mice rechallenged with CT26 cells. Taken together, our findings suggest that an on-site hydrogel-based micro-network of TLN has the potential to remodel the tumor immune microenvironment. Although we used TLN in this study, the concept could be extended to support the sustained action of other nanoadjuvants in a hydrogel micro-network.

Nanoparticles for Lymph Node-Directed Delivery.

Lymph nodes are organs that control immune cells and provide a major pathway for primary tumors to metastasize. A nanoparticles-based strategy has several advantages that make it suitable for achieving effective lymphatic delivery. First, the size of nanoparticles can be tailored to meet a size range appropriate for lymphatic migration. In addition, functionalized nanoparticles can target cells of interest for delivery of drugs or imaging probes. Existing lymph node contrast agents map all lymph nodes regardless of metastasis status; however, by using nanoparticles, it is possible to selectively target lymphatic metastases. Moreover, using functionalized nanoparticles, it is possible to specifically deliver anticancer drugs to metastatic lymph nodes. In this review, we introduce the use of nanoparticles for lymphatic mapping, in particular highlighting design considerations for detecting metastatic lymph nodes. Furthermore, we assess trends in lymph node-targeting nanoparticles in clinical practice and suggest future directions for lymph node-targeting nanoparticles.

Blood-declustering excretable metal clusters assembled in DNA matrix.

We report polymeric DNA-supported gold clusters that achieve interparticle plasmon-coupling, generate immunotherapeutic effects at the tumor tissue, but decluster in the bloodstream. As immunostimulating DNA, we used polyCpG DNA, which could act as a supporting matrix for metal clusters, enabling the clusters to decluster in the bloodstream. We constructed polyCpG-supported gold nanoclusters (AuPCN). For comparison with AuPCN, monomer CpG-bound gold nanoparticles (AuMC) were used. Unlike AuMC, AuPCN showed an interparticle plasmon-coupling effect and a higher light-to heat conversion efficiency. In the serum, AuPCN declustered to subunits. The CT26 tumor rechallenge of mice pretreated with AuPCN(+NIR) was followed by 0% tumor recurrence and 100% survival for up to 80 days. Compared with other groups, AuPCN(+NIR)-treated mice revealed greater cytotoxic T cell-infiltration in distant tumors and higher memory T cells in the lymph nodes. Until 7 days post-dose, the urinary excretion of Au was observed in the AuPCN-treated group, but not in the Au nanoparticle-treated mice. Although we used gold clusters and concatemeric immunostimulatory CpG as components of AuPCN, the concept of declustering in the bloodstream can be applied to design other functional DNA scaffold-based metal clusters with reduced concerns for long-term retention in the body.

DNA-cloaked nanoparticles for tumor microenvironment-responsive activation.

Although progress has been made in developing tumor microenvironment-responsive delivery systems, the list of cargo-releasing stimuli remains limited. In this study, we report DNA nanothread-cloaked nanoparticles for reactive oxygen species (ROS)-rich tumor microenvironment-responsive delivery systems. ROS is well known to strongly induce DNA fragmentation via oxidative stress. As a model anticancer drug, hydrophobic omacetaxine was entrapped in branched cyclam ligand-modified nanoparticles (BNP). DNA nanothreads were prepared by rolling-circle amplification and complexed to BNP, yielding DNA nanothread-cloaked BNP (DBNP). DBNP was unmasked by DNA nanothread-degrading ROS and culture supernatants of LNCaP cells. The size and zeta potential of DBNP were changed by ROS. In ROShigh LNCaP cells, but not in ROSlow fibroblast cells, the uptake of DBNP was higher than that of other nanoparticles. Molecular imaging revealed that DBNP exhibited greater distribution to tumor tissues, compared to other nanoparticles. Ex vivo mass spectrometry-based imaging showed that omacetaxine metabolites were distributed in tumor tissues of mice treated with DBNP. Intravenous administration of DBNP reduced the tumor volume by 80% compared to untreated tumors. Profiling showed that omacetaxine treatment altered the transcriptional profile. These results collectively support the feasibility of using polymerized DNA-masked nanoparticles for selective activation in the ROS-rich tumor microenvironment.

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy.

In immunotherapy, ex vivo stimulation of T cells requires significant resources and effort. Here, we report artificial dendritic cell-mimicking DNA microflowers (DM) for programming T cell stimulation in situ. To mimic dendritic cells, DNA-based artificial dendritic microflowers were constructed, surface-coated with polydopamine, and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM (DM-A). The porous structure of DM-A allowed entrapment of the T cell-stimulating cytokine, ineterleukin-2, yielding interleukin-2-loaded DM-A (DM-AI). For comparison, polystyrene microparticles coated with polydopamine and modified with anti-CD3 and anti-CD28 antibodies (PS-A) were used. Compared to PS-A, DM-AI showed significantly greater contact with T cell surfaces. DM-AI provided the highest ex vivo expansion of cytotoxic T cells. Local injection of DM-AI to tumor tissues induced the recruitment of T cells and expansion of cytotoxic T cells in tumor microenvironments. Unlike the other groups, model animals injected with DM-AI did not exhibit growth of primary tumors. Treatment of mice with DM-AI also protected against growth of a rechallenged distant tumor, and thus prevented tumor recurrence in this model. DM-AI has great potential for programmed stimulation of CD8+ T cells. This concept could be broadly extended for the programming of specific T cell stimulation profiles.

Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis.

In liver fibrosis, activated hepatic stellate cells are known to overexpress fibroblast activation protein. Here we report a targeted antifibrotic peptide-delivery system in which fibroblast activation protein, which is overexpressed in fibrotic regions of the liver, liberates the antifibrotic peptide melittin by cleaving a fibroblast activation protein-specific site in the peptide. The promelittin peptide is linked to pegylated and maleimide-functionalized liposomes, resulting in promelittin-modified liposomes. The promelittin-modified liposomes were effective in reducing the viability of activated hepatic stellate cells but not that of control cells. In three types of liver fibrosis mouse models, intravenously administered promelittin-modified liposomes significantly reduces fibrotic regions. In addition, in the bile duct ligation mouse model promelittin-modified liposome-treatment increases overall survival. Although this peptide-delivery concept was tested for liver fibrosis, it can potentially be adapted to other fibrotic diseases.

Lipid-based nanoparticles for photosensitive drug delivery systems.

Background: Numerous drug delivery strategies have been studied, but many hurdles exist in drug delivery rates to the target site. Recently, researchers have attempted to remotely control the in vivo behavior of drugs with light to overcome the shortcomings of conventional drug delivery systems. Photodynamic and photothermal systems are representative strategies wherein a photosensitive material is activated in response to a specific wavelength of light. Area covered: Photosensitive materials generally exhibit poor solubility and low biocompatibility. Additionally, their low photostability negatively affects delivery performance. A formulation of lipid-based nanoparticles containing photosensitive substances can help achieve photosensitive drug delivery with improved biocompatibility. The lipid bilayer structure, which can be assembled and disassembled by modulating the surrounding conditions (temperature, pH, etc.), can also be crucial for controlled release of drugs. Expert opinion: To the best of our knowledge, translation research on photoresponsive nanoparticles is scarce. However, as various drugs based on lipid nanoparticles have been clinically approved, the development potential of the lipid-based photoresponsive nanoparticles seems high. Thus, the identification of valid indications and development of optimum medical devices will increase the interest in photoresponsive material-based nanoparticles.

Genome-Editing-Mediated Restructuring of Tumor Immune Microenvironment for Prevention of Metastasis.

Modulating the tumor immune microenvironment to activate immune cells has been investigated to convert cold to hot tumors. Here, we report that metal-lipid hybrid nanoparticle (MLN)-mediated gene editing of transforming growth factor-ß (TGF-ß) can restructure the tumor microenvironment to an "immune activated" state for subsequent immunotherapy. MLNs with cationic lipids and elemental metallic Au inside were designed to deliver plasmid DNA encoding TGF-ß single guide RNA and Cas9 protein (pC9sTgf) and to convert near-infrared light (NIR) to heat. Upon NIR irradiation, MLNs induced photothermal anticancer effects and calreticulin exposure on B16F10 cancer cells. Lipoplexes of pC9sTgf and MLN (pC9sTgf@MLN) provided gene editing of B16F10 cells and in vivo tumor tissues. In mice treated with pC9sTgf@MLNs and NIR irradiation, the tumor microenvironment showed increases in mature dendritic cells, cytotoxic T cells, and interferon-γ expression. In B16F10 tumor-bearing mice, intratumoral injection of pC9sTgf@MLNs and NIR irradiation resulted in ablation of primary tumors. Application of pC9sTgf@MLNs and NIR irradiation prevented the growth of secondarily challenged B16F10 cells at distant sites and B16F10 lung metastasis. Combined TGF-ß gene editing and phototherapy is herein supported as a modality for restructuring the tumor immune microenvironment and preventing tumor recurrence.

Fibrinolytic nanocages dissolve clots in the tumor microenvironment, improving the distribution and therapeutic efficacy of anticancer drugs.

Fibrin, one of the components of the extracellular matrix (ECM), acts as a transport barrier within the core of tumors by constricting the blood vessels and forming clots, leading to poor intratumoral distribution of anticancer drugs. Our group previously developed a microplasmin-based thrombolytic ferritin nanocage that efficiently targets and dissolves clots without causing systemic fibrinolysis or disrupting hemostatic clots. We hypothesized that the thrombolytic nanocage-mediated degradation of fibrin clots in the tumor ECM can lead to enhanced intratumoral drug delivery, especially for nanosized anticancer drugs. Fibrin clot deposition worsens after surgery and chemotherapy, further hindering drug delivery. Moreover, the risk of venous thromboembolism (VTE) also increases. Here, we used thrombolytic nanocages with multivalent clot-targeting peptides and fibrin degradation enzymes, such as microplasmin, to dissolve fibrin in the tumor microenvironment and named them fibrinolytic nanocages (FNCs). These FNCs target tumor clots specifically and effectively. FNCs efficiently dissolve fibrin clots inside of the tumor vessels, suggesting that they can mitigate the risk of VTE in cancer patients. Coadministration of FNC and doxorubicin led to improved chemotherapeutic activity in a syngeneic mouse melanoma model. Furthermore, the FNCs increased the distribution of Doxil/doxorubicin nanoparticles within mouse tumors. These results suggest that fibrinolytic cotherapy might help improve the therapeutic efficacy of anticancer nanomedicines. Thus, microplasmin-based fibrinolytic nanocages are promising candidates for this strategy due to their hemostatic safety and ability to home in on the tumor.

Cell membrane-derived vesicles for delivery of therapeutic agents.

Cell membranes have recently emerged as a new source of materials for molecular delivery systems. Cell membranes have been extruded or sonicated to make nanoscale vesicles. Unlike synthetic lipid or polymeric nanoparticles, cell membrane-derived vesicles have a unique multicomponent feature, comprising lipids, proteins, and carbohydrates. Because cell membrane-derived vesicles contain the intrinsic functionalities and signaling networks of their parent cells, they can overcome various obstacles encountered in vivo. Moreover, the different natural combinations of membranes from various cell sources expand the range of cell membrane-derived vesicles, creating an entirely new category of drug-delivery systems. Cell membrane-derived vesicles can carry therapeutic agents within their interior or can coat the surfaces of drug-loaded core nanoparticles. Cell membranes typically come from single cell sources, including red blood cells, platelets, immune cells, stem cells, and cancer cells. However, recent studies have reported hybrid sources from two different types of cells. This review will summarize approaches for manufacturing cell membrane-derived vesicles and treatment applications of various types of cell membrane-derived drug-delivery systems, and discuss challenges and future directions.

Lipid Nanoparticle-Mediated Lymphatic Delivery of Immunostimulatory Nucleic Acids.

Lymphatic delivery of a vaccine can be achieved using a dendritic cell (DC)-targeted delivery system that can cause DC to migrate to lymph nodes upon activation by an adjuvant. Here, we designed a mannose-modified cationic lipid nanoparticle (M-NP) to deliver the nucleic acid adjuvant, polyinosinic:polycytidylic acid (PIC). PIC-loaded M-NP (PIC/M-NP) showed stable lipoplexes regardless of the ligand ratio and negligible cytotoxicity in bone marrow-derived DC. DC uptake of PIC/M-NP was demonstrated, and an increased mannose ligand ratio improved DC uptake efficiency. PIC/M-NP significantly promoted the maturation of bone marrow-derived DC, and local injection of PIC/M-NP to mice facilitated lymphatic delivery and activation (upon NP uptake) of DC. Our results support the potential of PIC/M-NP in delivering a nucleic acid adjuvant for the vaccination of antigens.

Melanin-loaded CpG DNA hydrogel for modulation of tumor immune microenvironment.

Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment, but this strategy has suffered from the lack of biodegradability of the photoresponsive materials. In this study, we aimed to develop biodegradable materials for photothermal immunotherapy. To this end, we designed a DNA CpG hydrogel (DH, generated by rolling-circle amplification), loaded it with bis-(3'-5')-cyclic dimeric guanosine monophosphate (G/DH), and coated the formulation with melanin (Mel/G/DH). Mel/G/DH exhibited a temperature increase upon near infrared (NIR) illumination. In vitro, Mel/G/DH plus NIR (808 nm) irradiation, induced the exposure of calreticulin on CT26 cancer cells, and significantly activated the maturation of dendritic cells (DC). In vivo, local administration of Mel/G/DH (+NIR) exerted photothermal killing of primary tumors and induced maturation of DC in lymph nodes. Treatment of primary tumors with Mel/G/DH(+NIR) prevented the growth of rechallenged tumors at a distant site. Survival was 100% in mice treated with Mel/G/DH(+NIR), 5-fold higher than the group treated with Mel/G(+NIR). Mel/G/DH(+NIR) treatment remodeled the immune microenvironment of distant tumors, increasing cytotoxic T cells and decreasing Treg cells. Taken together, the results of this study suggest the potential of Mel/G/DH as a platform for modulating tumor immune microenvironment aimed at preventing the recurrence of distant tumors.

Molecular engineering of antibodies for site-specific conjugation to lipid polydopamine hybrid nanoparticles.

Conjugation of antibodies to nanoparticles allows specific cancer targeting, but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody. Here, a molecular engineering technique was used for site-specific conjugation of antibodies to nanoparticles. We designed an anti-claudin 3 (CLDN3) antibody containing a single cysteine residue, h4G3cys, then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles (LPNs). Because of their negatively charged lipid coating, LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4G3cys. The activity of h4G3cys was tested by measuring the binding of h4G3cys-conjugated LPNs (C-LPNs) to CLDN3-positive tumor cells and assessing its subsequent photothermal effects. C-LPNsspecifically recognized CLDN3-overexpressing T47D breast cancer cells but not CLDN3-negative Hs578T breast cancer cells. High binding of C-LPNs to CLDN3-overexpressing T47D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy. Consistent with this, intravenous injection of C-LPNsin a T47D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases. Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.

Photosensitizer-Trapped Gold Nanocluster for Dual Light-Responsive Phototherapy.

Photoresponsive nanomaterials have recently received great attention in the field of cancer therapy. Here, we report a photosensitizer-trapped gold nanocluster that can facilitate dual light-responsive cancer therapy. We utilized methylene blue (MB) as a model photosensitizer, gold nanocluster as a model photothermal agent, and a polymerized DNA as the backbone of the nanocluster. We synthesized MB-intercalated gold DNA nanocluster (GMDN) via reduction and clustering of gold ions on a template consisting of MB-intercalated long DNA. Upon GMDN treatment, cancer cells revealed clear cellular uptake of MB and gold clusters; following dual light irradiation (660 nm/808 nm), the cells showed reactive oxygen species generation and increased temperature. Significantly higher cancer cell death was observed in cells treated with GMDN and dual irradiation compared with non-irradiated or single light-irradiated cells. Mice systemically injected with GMDN showed enhanced tumor accumulation compared to that of free MB and exhibited increased temperature upon near infrared irradiation of the tumor site. Tumor growth was almost completely inhibited in GMDN-treated tumor-bearing mice after dual light irradiation, and the survival rate of this group was 100% over more than 60 days. These findings suggest that GMDN could potentially function as an effective phototherapeutic for the treatment of cancer disease.

Tannic acid-functionalized boron nitride nanosheets for theranostics.

Here, we report a tannic acid-Fe3+ coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.e., dopamine, 3,4-dihydroxyphenylacetic acid, gallic acid, and tannic acid), a coating of tannic acid-Fe3+ coordination complex provided the highest magnetic field relaxivity and near infrared (NIR) laser light responsiveness. An in vitro study showed that KB tumor cells treated with tannic acid-Fe3+ coordination complex adsorbed on BNS (TA-Fe/BNS) exhibited higher T1-weighted magnetic resonance contrast compared with plain BNS, and BNS coated with tannic acid or Fe alone. NIR irradiation at 808 nm caused a significant increase in KB tumor cell death after treatment with TA-Fe/BNS compared with other treatments. In vivo MRI imaging revealed tumor accumulation of intravenously administered TA-Fe/BNS. Guided by MRI information, application of focused laser irradiation onto tumor tissues resulted in complete tumor ablation. These results support the potential of TA-Fe/BNS for MRI theranostics. Moreover, this study suggests the wide applicability of TA-Fe noncovalent coating as biocompatible and facile tool for converting nonfunctional early-generation nanomaterials into functional new nanomaterials, opening new opportunities for their use in translational biomedical applications such as MRI theranostics.