Theranostic Capabilities Research Articles

Bio-inspired sustainable electrospun quantum nanostructures for high quality factor enabled face masks and self-powered intelligent theranostics

Plastic pollution, the energy crisis, and climate change are significant global challenges that threaten human sustainability and social development. Additionally, addressing pollution while simultaneously promoting valorization techniques for the development of effective personal protective equipment to mitigate the transmission of the SARS-CoV-2 virus poses a challenge, particularly in maintaining wearer comfort. Current advancements in intelligent future therapies focus on the incorporation of quantum nanostructures with theranostic capabilities that are compatible with the skin, reduce wear interference, and facilitate easy integration into minimally invasive surgical procedures. To address these challenges, we propose a win–win strategy that enables microplasma technology and high-throughput electrospinning technology to prepare sustainable self-powered angiogenesis inspired ultrafine nanofibers (AINFs). The proposed quantum nanostructure-anchored AINFs are designed to support the development of flex-insensitive white light-emitting optoelectronics (92 % at 500 cycles), COVID-19 face masks of record high-quality factors (0.167 Pa−1 @ PM0.2), and highly compatible large-scale self-powered theranostic capabilities (2694 pmV−1). These innovations align with the urgent demands of a circular economy and foster environmentally sustainable applications within the Internet of Medical Things.

Evaluation of Targeted Alpha Therapy Using [211At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion. Consequently, it is hypothesized that the Astatine (211At)-labeled FAP inhibitor (FAPI) selectively exerts anti-tumor effects through alpha-particle emission. In this study, we aimed to assess its theranostic capabilities by integrating [18F]FAPI-74 PET imaging with targeted alpha therapy using [211At]FAPI1 in TNBC models. Mice xenografts were established by transplanting MDA-MB-231 and HT1080 cells (control). As a parallel diagnostic method, [18F]FAPI-74 was administered for PET imaging to validate FAP expression. A single dose of [211At]FAPI1 (1.04 ± 0.10 MBq) was administered to evaluate the therapeutic efficacy. [18F]FAPI-74 exhibited high accumulation in MDA-MB-231 xenografts, and FAP expression was pathologically confirmed via immunostaining. The group that received [211At]FAPI1 (n = 11) demonstrated a significantly enhanced anti-tumor effect compared with the control group (n = 7) (p = 0.002). In conclusion, [18F]FAPI-74 PET imaging was successfully used to diagnose FAP expression, and as [211At]FAPI1 showed promising therapeutic efficacy in TNBC models, it is expected to be a viable therapeutic option.

Carrier-Free Biomimetic Organic Nanoparticles with Super-High Drug Loading for Targeted NIR-II Excitable Triple-Modal Bioimaging and Phototheranostics.

Multimodal near-infrared II (NIR-II) theranostics combined with nanotechnology have emerged as promising treatments for cancer due to their noninvasive and high spatiotemporal nature. Traditional NIR-II theranostics typically comprise useless and massive inert carriers, resulting in low drug loading capacity, reduced therapeutic effects, and potential biotoxicity. To overcome these limitations, this work reports carrier-free NIR-II theranostics simultaneously with high drug loading capacity and multimodal NIR-II imaging capabilities for cancer phototheranostics in the NIR-II window. Carrier-free BTA nanoparticles (NPs) are prepared by self-assembling the NIR-II responsive conjugated oligomer BTA without adding coating agents; these NPs exhibited 100% drug loading and high-performance NIR-II theranostic capabilities. Cancer cell membranes are camouflaged on carrier-free BTA NPs to provide homologous targeting ability, enhanced stability, and 77.8% drug loading. Both in vitro and in vivo studies have indicated that biomimetic NPs provide efficient triple-modal guidance for NIR-II fluorescence, photoacoustic, and photothermal imaging and complete tumor elimination via photothermal therapy (PTT). Additionally, theranostics-based treatments with good biosecurity are demonstrated. This study contributes a new strategy for the design of high-drug-loading NIR-II theranostics and further promotes the clinical translation of theranostic agents.

Nanoparticles use magnetoelectricity to target and eradicate cancer cells.

We investigated the theranostic capabilities of magnetoelectric nanoparticles (MENPs) combined with MRI via a murine model of pancreatic adenocarcinoma. MENPs leverage the magnetoelectric effect to convert an applied magnetic field into local electric fields, which can induce irreversible electroporation of tumor cell membranes when activated by MRI. Additionally, MENPs modulate MRI relaxivity, which can be used to predict the degree of tumor ablation. Through a pilot study (n=21) and a confirmatory study (n=27), we demonstrated that, ≥300 µg of MRI-activated MENPs significantly reduced tumor volumes, averaging a three-fold decrease as compared to controls. Furthermore, there was a direct correlation between the reduction in tumor T 2 relaxation times and tumor volume reduction, highlighting the predictive prognostic value of MENPs. Six of 17 mice in the confirmatory study's experimental arms achieved a durable complete response, showcasing the potential for durable treatment outcomes. Importantly, the administration of MENPs was not associated with any evident toxicities. This study presents the first in vivo evidence of an externally controlled, MRI-based, theranostic agent that effectively targets and treats solid tumors via irreversible electroporation while sparing normal tissues, offering a new and promising approach to cancer therapy.

MRI detection of free-contrast agent nanoparticles.

The integration of nanotechnology into biomedical imaging has significantly advanced diagnostic and theranostic capabilities. However, nanoparticle detection in imaging relies on functionalization with appropriate probes. In this work, a new approach to visualize free-label nanoparticles using MRI and MRS techniques is described, consisting of detecting by 1H CSI specific proton signals belonging to the components naturally present in most of the nanosystems used in preclinical and clinical research. Three different nanosystems, namely lipid-based micelles, liposomes, and perfluorocarbon-based nanoemulsions, were synthesized, characterized by high resolution NMR and then visualized by 1H CSI at 300 MHz. Subsequently the best 1H CSI performing system was administered to murine models of cancer to evaluate the possibility of tracking the nanosystem by looking at its proton associated signal. Furthermore, an in vitro comparison between 1H CSI and 19F MRI was carried out. The study successfully demonstrates the feasibility of detecting nanoparticles using MRI/MRS without probe functionalization, employing 1H CSI. Among the nanosystems tested, the perfluorocarbon-based nanoemulsion exhibited the highest SNR. Consequently, it was evaluated in vivo, where its detection was achievable within tumors and inflamed regions via 1H CSI, and in lymph nodes via PRESS. These findings present a promising avenue for nanoparticle imaging in biomedical applications, offering potential enhancements to diagnostic and theranostic procedures. This non-invasive approach has the capacity to advance imaging techniques and expand the scope of nanoparticle-based biomedical research. Further exploration is necessary to fully explore the implications and applications of this method.

Gastrin-releasing peptide receptor as theranostic target in estrogen-receptor positive breast cancer: A preclinical study of the theranostic pair [55Co]Co- and [177Lu]Lu-DOTA-RM26

BackgroundPatients with advanced metastatic estrogen receptor-positive breast cancer often develop resistance to standard treatments, leading to uncontrolled progression. Thus, innovative therapies are urgently needed. The gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers, including breast cancer, making it an interesting theranostic target. RM26, a GRPR-targeting antagonist, has demonstrated promising in vivo kinetics in prostate cancer models. This study evaluated the theranostic capabilities of [55Co]Co−/[177Lu]Lu-DOTA-RM26 in vitro in estrogen receptor-positive breast cancer cells and assessed the diagnostic potential of [55Co]Co-DOTA-RM26 in vivo in a breast cancer mouse model. MethodsWe analyzed the binding specificity of [57Co]Co-/[177Lu]Lu-DOTA-RM26 in T47D breast cancer cells, using [57Co]Co-DOTA-RM26 as a surrogate for [55Co]Co-DOTA-RM26. The therapeutic efficacy of increasing [177Lu]Lu-DOTA-RM26 concentrations was determined via viability assay in vitro. Ex vivo biodistribution of [57Co]Co-DOTA-RM26 (17.2 ± 2.7 kBq, 33 ± 5.2 pmol/mouse) was investigated in 12 mice (n= 4/group) with orthotopic breast cancer tumors. The mice were sacrificed at 4 and 24 h post-injection (pi), including a blocking group (20 nmol of unlabeled [Tyr4]-Bombesin) at 4 h pi. For imaging, two tumor-bearing mice underwent [55Co]Co-DOTA-RM26 PET/CT, 4 and 24 h pi (2.8 ± 0.2 MBq, 167.5 ± 0.5 pmol/mouse), with or without GRPR blocking. ResultsIn vitro studies revealed high, specific binding of [57Co]Co-DOTA-RM26 (43 ± 1 % of total added activity per 106 cells (%IA/106)) and [177Lu]Lu-DOTA-RM26 (37 ± 4 %IA/106). The activity was predominantly localized at the cell surface: 71 ± 3 % and 80 ± 6 % for [57Co]Co-DOTA-RM26 and [177Lu]Lu-DOTA-RM26, respectively. [177Lu]Lu-DOTA-RM26 significantly reduced cell viability at all activity concentrations >0.625 MBq/mL (p < 0.0001), with cell viability below 1 % at concentrations ≥5 MBq/mL. Biodistribution data (n = 12) indicated a high, specific tumor uptake of [57Co]Co-DOTA-RM26, surpassing all other tissues significantly at both time points, 3.7 ± 0.6 % of the injected activity per gram (%IA/g) 4 h pi and 0.98 ± 0.05 %IA/g 24 h pi. The kidneys showed the second-highest uptake (2.0 ± 0.1 %IA/g 4 h pi), followed by the pancreas (1.4 ± 0.4 %IA/g 4 h pi). PET/CT imaging with [55Co]Co-DOTA-RM26 supported the biodistribution data and, distinctly visualized the tumor 24 h pi and showed an improved tumor-to-background compared to the earlier time points. Effective GRPR blocking significantly reduced tumor uptake in the PET images 24 h pi. ConclusionThese findings suggest that the theranostic pair [55Co]Co−/[177Lu]Lu-DOTA-RM26 holds significant promise as a theranostic agent for estrogen receptor-positive breast cancer.

Development of a Polymer Ultrasound Contrast Agent Incorporating Nested Carbon Nanodots

Polymer microbubbles have garnered broad interest as potential theranostic agents. However, the capabilities of polymer MBs can be greatly enhanced, particularly regarding the imaging performance and functional versatility of the platform. This study investigates integrating fluorescent carbon nanodots within polylactic acid (PLA) microbubbles. First, the formulations are characterized by their size, microbubble counts, zeta potential, and resonance frequency. Then, the fluorescence capabilities, nanoparticle loading, and acoustic capabilities are examined. Unmodified (U-), carboxylated (C-), and aminated graphene quantum dots (A-GQDs) were separately suspended and synthesized at a 2% w/w ratio with PLA in the organic phase of the water/oil/water double emulsion process. The new microbubbles were characterized using an AccuSizer, Zetasizer, scanning electron microscopy, fluorescence microscopy and fluorimetry, a custom-built acoustic setup, and clinical ultrasound. The GQD microbubbles were sized between 1.4 and 1.9 µm (U = 1.90, C = 1.44, A = 1.72, Unloaded = 2.02 µm). The U-GQD microbubble exhibited a higher bubble concentration/mg PLA ( p &lt; .05) and the A-GQD microbubbles exhibited the greatest shift in zeta potential. Electron microscopy revealed smooth surfaces and a spherical shape, showing that the nanoparticle addition was not deleterious. The A-GQD microbubbles were specifically detectable using DAPI-filtering with fluorescence microscopy and had the highest TRITC-filtered fluorescence. The C-GQD microbubbles had the highest loading efficiency at 59.4% ( p &lt; .05), and the lowest max acoustic enhancement at 5 MHz (U = 19.8, C = 17.6, A = 18.9, Unloaded = 18.5 dB; p &lt; .05). Additionally, all microbubbles were visible and susceptible to inertial cavitation utilizing clinical ultrasound. The A-GQDs showed promise toward improving the theranostic capabilities of the microbubble platform. They have imbued the most advantageous fluorescence capability and slightly improved backscatter enhancement while retaining all the necessary capabilities of an ultrasound contrast agent. Future studies will investigate the coloading potential of A-GQDs and drug within microbubbles.

Ultrasound-responsive theranostic platform for the timely monitoring and efficient thrombolysis in thrombi of tPA resistance

There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Engineering Tumor‐Specific Nanotheranostic Agent with MR Image‐Guided NIR‐II &amp; ‐III Photodynamic Therapy to Combat Against Deeply Seated Orthotopic Glioblastoma

Glioblastoma multiforme (GBM) is one of the most aggressive, incurable, and difficult‐to‐treat malignant brain tumor with very poor survival rates. The gold standard in treating GBMs includes neurosurgical resection of the tumor, followed by the chemotherapy and radiotherapy. However, these strategies remain ineffective in treating patients with GBMs, as tumor recurrence always occur in most cases. Therefore, it remains a grand challenge to develop an effective strategy to combat orthotopic glioblastoma with simultaneous imaging capabilities to monitor the therapeutic outcomes. To tackle this challenge, this study demonstrates, for the first time, that a tumor‐specific europium hexaboride (EuB6)‐based nanomedicine surface‐modified with RGD‐K peptide to target αvβ3 integrin receptors overexpressed on the glioblastoma cells. Further, EuB6@RGD‐K NPs are able to exert theranostic capabilities to effectively diagnose and combat difficult‐to‐treat orthotopic glioblastoma tumors using NIR‐II 1064 nm and NIR‐III 1550 nm photodynamic therapy (NIR PDT) effects. In the in vivo experiments, the average half‐life of 55 d for mice treated with EuB6@RGD‐K NPs and exposed to NIR‐III 1550 nm light irradiation is far higher than that of EuB6@RGD‐K NPs exposed to NIR‐II 1064 nm light irradiation (25 d), PBS‐treated mice (20 d) and EuB6@RGD‐K NPs‐treated mice (no light irradiation, 18 d). To the best of our knowledge, this work represents the first example for destructing murine brain tumors via multi‐functional tumor‐specific europium hexaboride‐based nanotheranostic agent to mediate MR imaging‐guided NIR‐II/‐III photodynamic therapy.

MXene-based composites in smart wound healing and dressings.

MXenes, a class of two-dimensional materials, exhibit considerable potential in wound healing and dressing applications due to their distinctive attributes, including biocompatibility, expansive specific surface area, hydrophilicity, excellent electrical conductivity, unique mechanical properties, facile surface functionalization, and tunable band gaps. These materials serve as a foundation for the development of advanced wound healing materials, offering multifunctional nanoplatforms with theranostic capabilities. Key advantages of MXene-based materials in wound healing and dressings encompass potent antibacterial properties, hemostatic potential, pro-proliferative attributes, photothermal effects, and facilitation of cell growth. So far, different types of MXene-based materials have been introduced with improved features for wound healing and dressing applications. This review covers the recent advancements in MXene-based wound healing and dressings, with a focus on their contributions to tissue regeneration, infection control, anti-inflammation, photothermal effects, and targeted therapeutic delivery. We also discussed the constraints and prospects for the future application of these nanocomposites in the context of wound healing/dressings.

AGuIX nanoparticle-nanobody bioconjugates to target immune checkpoint receptors.

This article presents bioconjugates combining nanoparticles (AGuIX) with nanobodies (VHH) targeting Programmed Death-Ligand 1 (PD-L1, A12 VHH) and Cluster of Differentiation 47 (CD47, A4 VHH) for active tumor targeting. AGuIX nanoparticles offer theranostic capabilities and an efficient biodistribution/pharmacokinetic profile (BD/PK), while VHH's reduced size (15 kDa) allows efficient tumor penetration. Site-selective sortagging and click chemistry were compared for bioconjugation. While both methods yielded bioconjugates with similar functionality, click chemistry demonstrated higher yield and could be used for the conjugation of various VHH. The specific targeting of AGuIX@VHH has been demonstrated in both in vitro and ex vivo settings, paving the way for combined targeted immunotherapies, radiotherapy, and cancer imaging.

Illuminating and Radiosensitizing Tumors with 2DG-Bound Gold-Based Nanomedicine for Targeted CT Imaging and Therapy.

Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.

Synergistic Phenomena between Iron-Doped ZnO Nanoparticles and Shock Waves Exploited against Pancreatic Cancer Cells.

We propose the use of iron-doped zinc oxide nanoparticles (Fe:ZnO NPs) showing theranostic capabilities and being synergistically active against pancreatic ductal adenocarcinoma once combined with mechanical pressure waves, such as shock waves. Fe:ZnO NPs are synthesized by employing oleic acid as a capping agent and are functionalized with amino-propyl groups. We first report their superior characteristics with respect to undoped ZnO NPs in terms of magnetic properties, colloidal stability, cytocompatibility, and internalization into BxPC-3 pancreatic cancer cells in vitro. These Fe:ZnO NPs are also cytocompatible toward normal pancreatic cells. We then perform a synergistic cell treatment with both shock waves and Fe:ZnO NPs once internalized into cells. We also evaluate the contribution to the synergistic activity of the NPs located in the extracellular space. Results show that both NPs and shock waves, when administered separately, are safe to cells, while their combination provokes an enhanced cell death after 24 h. Various mechanisms are then considered, such as dissolution of NPs, production of free radicals, and cell membrane disruption or permeation. It is understood so far that iron-doped ZnO NPs can degrade intracellularly into zinc cations, while the use of shock waves produce cell membrane permeabilization and possible rupture. In contrast, the production of reactive oxygen species is here ruled out. The provoked cell death can be recognized in both apoptotic and necrotic events. The proposed work is thus a first proof-of-concept study enabling promising future applications to deep-seated tumors such as pancreatic cancer, which is still an unmet clinical need with a tremendous death rate.

Near-Infrared Fluorescent Probes as Imaging and Theranostic Modalities for Amyloid-Beta and Tau Aggregates in Alzheimer's Disease.

A person suspected of having Alzheimer's disease (AD) is clinically diagnosed for the presence of principal biomarkers, especially misfolded amyloid-beta (Aβ) and tau proteins in the brain regions. Existing radiotracer diagnostic tools, such as PET imaging, are expensive and have limited availability for primary patient screening and pre-clinical animal studies. To change the status quo, small-molecular near-infrared (NIR) probes have been rapidly developed, which may serve as an inexpensive, handy imaging tool to comprehend the dynamics of pathogenic progression in AD and assess therapeutic efficacy in vivo. This Perspective summarizes the biochemistry of Aβ and tau proteins and then focuses on structurally diverse NIR probes with coverages of their spectroscopic properties, binding affinity toward Aβ and tau species, and theranostic effectiveness. With the summarized information and perspective discussions, we hope that this paper may serve as a guiding tool for designing novel in vivo imaging fluoroprobes with theranostic capabilities in the future.

Hydrogen-Bonds-Mediated Nanomedicine: Design, Synthesis, and Applications.

Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug- and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.

Near-Infrared Light Activatable Two-Dimensional Nanomaterials for Theranostic Applications: A Comprehensive Review

Two-dimensional (2D) layered nanomaterials possess high surface area, unique structure, and extraordinary physicochemical, optical, and electrical properties and have attracted tremendous interests in the field of biomedical research. Several types of 2D nanomaterials, including graphene and its derivatives, black phosphorus (BP) nanosheets, graphitic carbon nitride, MXenes, and transition metal dichalcogenides (TMDCs), have been extensively utilized for phototheranostic applications. Besides their unique optical properties and high surface area, these nanomaterials can facilitate loading of different guest molecules for enabling phototherapeutic outcomes. Furthermore, various other nanoparticles or molecules can be decorated to improve the optical absorption in the near-infrared (NIR) region, biocompatibility, and achieve excellent theranostic capabilities which make them promising candidates for future biomedical/clinical applications. Herein, we review the recent progress of NIR light activatable 2D nanomaterials for theranostic applications. The current challenges and future perspectives have also been discussed.

Targeted Theranostic 111In/Lu-Nanotexaphyrin for SPECT Imaging and Photodynamic Therapy.

Theranostic nanoparticles aim to integrate diagnostic imaging and therapy to facilitate image-guided treatment protocols. Herein, we present a theranostic nanotexaphyrin for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and focal photodynamic therapy (PDT) accomplished through the chelation of metal isotopes (In, Lu). To realize nanotexaphyrin's theranostic properties, we developed a rapid and robust 111In/Lu-nanotexaphyrin radiolabeling method using a microfluidic system that achieved a high radiochemical yield (>90%). The optimized metalated nanotexaphyrin displayed excellent chemical, photo, and colloidal stabilities, potent singlet oxygen generation, and favorable plasma circulation half-life in vivo (t1/2 = 6.6 h). Biodistribution, including tumor accumulation, was characterized by NIR fluorescence, SPECT/CT imaging, and γ counting. Inclusion of the PSMA-targeting ligand enabled the preferential accumulation of 111In/Lu-nanotexaphyrin in PSMA-positive (PSMA+) prostate tumors (3.0 ± 0.3%ID/g) at 48 h with tumor vs prostate in a 2.7:1 ratio. In combination with light irradiation, the PSMA-targeting nanotexaphyrin showed a potent PDT effect and successfully inhibited PSMA+ tumor growth in a subcutaneous xenograft model. To the best of our knowledge, this study is the first demonstration of the inherent metal chelation-driven theranostic capabilities of texaphyrin nanoparticles, which, in combination with PSMA targeting, enabled prostate cancer imaging and therapy.

Sub-millimetre precision of drug delivery in the brain from ultrasound-triggered nanodroplets

Drug-loaded nanoscale cavitation agents, called nanodroplets, are an attractive solution to enhance and localize drug delivery, offering increased stability and prolonged half-life in circulation compared to microbubbles. However, the spatial precision with which drug can be released and delivered into brain tissue from such agents has not been directly mapped. Decafluorobutane lipid-shell droplets (206 +/− 6 nm) were loaded with a fluorescent blood-brain barrier (BBB)-penetrating dye (Nile Blue) and vaporized with ultrasound (1.66 MHz, 10 ms pulse length, 1 Hz pulse repetition frequency), generating transient echogenic microbubbles and delivering the encapsulated dye. The distribution and intensity of released fluorophore was mapped in a tissue-mimicking phantom, and in the brain of rats (Sprague Dawley, N = 4, n = 16). The release and distribution of dye was found to be pressure-dependent (0.2–3.5 MPa) and to occur only above the vaporization threshold of the nanodroplets (1.5 +/− 0.25 MPa in vitro, 2.4 +/− 0.05 MPa in vivo). Dye delivery was achieved with sub-millimetre spatial precision, covering an area of 0.4 to 1.5 mm in diameter, determined by the sonication pressure. The distribution and intensity of dye released at depth in the brain followed the axial pressure profile of the ultrasound beam. Nile Blue (354 Da, LogP 2.7) was compared to Nile Red (318 Da, LogP 3.8) and Quantum Dots (CdSe/ZnS, 5 nm diameter) to visualize the role of molecule size and lipophilicity in crossing the intact BBB following triggered release. Acoustic emissions were shown to predict the successful delivery of the BBB-penetrating dye and the extent of the distribution, demonstrating the theranostic capabilities of nanoscale droplets to precisely localize drug delivery in the brain.

Photosensitizing nanoclays for efficient cell uptake and in vitro photodynamic therapy

In this study a straightforward strategy to deliver photosensitizing molecules into cancer cells by using Laponite RD® (LAP) nanodisks as carrier is presented. We report the application of LAP functionalized with a highly hydrophobic Silicon phthalocyanine photosensitizer (SiPc) for efficient cell uptake and photodynamic therapy (PDT) of MCF-7 breast cancer cells in vitro. This inorganic-organic hybrid nanomaterial caused a threefold increase in intracellular ROS levels and 99.7% of cancer cell inactivation after light treatment (630 nm; fluency of 108 J/cm²). With its theranostic capabilities (simultaneous fluorescence and singlet oxygen generation), uptake into cancer cells was monitored to control the photo-inactivation. The functionalized nanodisks already proved to be an efficient photo-inactivator of pathogenic Gram-(+) bacteria and were previously reported as LS10. By extending the use of LS10 to PDT of cancer cells, it is an example of a photosensitizer functionalized nanoclay with multipurpose drug characteristics, demonstrating an intriguing potential for future phototherapeutic studies and applications.