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Purpose: Augmented reality (AR) is an innovative approach that could assist percutaneous procedures; by directly seeing "through" a phantom, targeting a lesion might be more intuitive than using ultrasound (US). The objective of this study was to compare the performance of experienced interventional radiologists and operators untrained in soft tissue lesion puncture using AR guidance and standard US guidance. Material and Methods: Three trained interventional radiologists with 5–10 years of experience and three untrained operators performed punctures of five targets in an abdominal phantom, with US guidance and AR guidance. Correct targeting, accuracy (defined as the Euclidean distance between the tip and the center of the target), planning time, and puncture time were documented. Results: Accuracy was higher for the trained group than the untrained group using US guidance (1 mm versus 4 mm, p = 0.001), but not when using AR guidance (4 mm vs. 4 mm, p = 0.76). All operators combined, no significant difference was found concerning accuracy between US and AR guidance (2 mm vs. 4 mm, p = 0.09), but planning time and puncture time were significantly shorter using AR (respectively, 15.1 s vs. 74 s, p < 0.001; 16.1 s vs. 59 s; p < 0.001). Conclusion: Untrained and trained operators obtained comparable accuracy in percutaneous punctures when using AR guidance whereas US performance was better in the experienced group. All operators together, accuracy was similar between US and AR guidance, but shorter planning time, puncture time were found for AR guidance. [ABSTRACT FROM AUTHOR]

Accurate and sensitive analysis of cancer‐associated microRNAs in living tissue is of great significance for the early diagnosis and treatment of cancer. Herein, a hierarchical nanoprobe denoted as UCNP‐QDs‐GNPs is delicately designed, where a near‐infrared (NIR) absorptive upconversion nanoparticle (UCNP) serves as the core, broad‐absorptive and bright emissive quantum dots (QDs) and emission‐quencher gold nanoparticles (GNPs) surround as satellites for microRNA imaging and image‐guided cancer therapy. Through the programmed assembly of heterobivalent DNA‐conjugated QDs with DNA‐modified GNPs and UCNPs, the well‐defined nanostructured UCNP‐QDs‐GNPs are generated with quenched fluorescence. Upon encountering the microRNA‐21 target, GNPs underwent catalytic disassembly, resulting in the concurrent recovery and amplification of fluorescence from QDs and UCNPs, which enabled sensitive imaging and quantification of microRNA‐21 within living cells. Furthermore, dithiol‐constituted aggregation‐induced emission (AIE) photosensitizers bonded on the surface of QDs, are effectively photosensitized by the QDs. The NIR excitation harvested by UCNPs is therefore efficiently transferred to QDs and subsequently converged on the AIE photosensitizers, boosting photodynamic activity for image‐guided therapy in deep‐seated tumors. The DNA‐programmed (de)hybridization strategy, facilitating the conversion of NIR excitation into imaging signals and photodynamic activity, offers a promising avenue for the early theranostics of malignancies. [ABSTRACT FROM AUTHOR]

High‐performance theranostic systems are of paramount importance for achieving precise image‐guided cancer immunotherapy. Here, a novel nanoplatform is presented that integrates aggregation‐induced emission luminogen (AIEgen) with prussian blue (PB) nanocatalyzer for robust cancer immunotherapy. The AIEgen with dimethylamine substitution demonstrates compelling near‐infrared (NIR) light‐induced photothermal conversion and photodynamic therapy (PDT) capabilities. By incorporating AIEgen into porous PBNPs, and further enveloped within M1 macrophage membrane, a tumor‐specific theranostic nanoagent is constructed. This strategic integration effectively constrains the molecular motion of AIEgen, leading to amplified NIR‐II fluorescence brightness and PDT attributes. Moreover, PBNPs can catalyze tumor‐overexpressed H2O2 to generate oxygen to boost PDT efficacy, and PB's NIR absorption also intensifies photoacoustic imaging and photothermal effect. The integration of NIR‐II fluorescence and photoacoustic imaging provides comprehensive information for photoimmunotherapy in orthotopic breast cancer‐bearing mice. Leveraging its potent immunogenic cell death effect, the nanoagent not only significantly inhibits cancer growth, but also generates a whole‐cell therapeutic cancer vaccine to protect mice from tumor rechallenge. In highly malignant post‐surgery breast cancer models, the nanoagent enables both accurate identification of residual tumors and efficient inhibition of postoperative tumor recurrence and pulmonary metastasis. This study will offer valuable insights for creating highly efficacious and multifaceted photoimmunotherapy protocols. [ABSTRACT FROM AUTHOR]

Image-guided disease treatment not only significantly enhances the efficacy of disease treatment but also minimizes unnecessary medication doses. Near-infrared II (NIR-II, 1000–1700 nm) bioimaging has been considered as one of the ideal bioimaging techniques in recent years due to its deep tissue penetration and low tissue fluorescence scattering. Here, we design the highly biocompatible lanthanide-doped nanoparticles NaYF4:Ce/Er@NaYbF4:Er@NaYF4:Nd-ZnPc/RB/mPEG-FA (RENPs-ZnPc/RB/mPEG-FA). Under an 808 nm excitation, the internal rare earth-doped nanoparticles (RENPs) can emit NIR-II luminescence for imaging. In addition, the generated upconversion luminescence in the visible region can be used as an excitation light source to excite the photosensitizers on the surface of the RENPs to generate singlet oxygen for antitumor photodynamic therapy. Based on the guidance of NIR-II imaging, the intratumoral injection approach is selected. During the treatment (day 7) after the second dose of RENPs-ZnPc/RB/mPEG-FA injection, the tumors are almost inhibited and eliminated, and there is no sign of recurrence in the follow-up observations. Interestingly, intravenously injected nanoparticles also enable high-resolution skeletal imaging with a high signal-to-background ratio, which holds promise for the clinical translation of RENPs-ZnPc/RB/mPEG-FA as versatile probes for imaging and therapy. [ABSTRACT FROM AUTHOR]

Bragg peak range uncertainties are a persistent constraint in proton therapy. Pulsed proton beams generate protoacoustic emissions proportional to absorbed proton energy, thereby encoding dosimetry information in a detectable acoustic wave. Here, we seek to derive and model 3D protoacoustic imaging with an ultrasound array and examine the frequency characteristics of protoacoustic emissions. A formalism is presented through which protoacoustic signals can be characterized considering transducer bandwidth as well as pulse duration of the incident beam. We have also collected an experimental proton beam intensity signal from a Mevion S250 clinical machine to analyze our formalism. We also show that proton-acoustic image reconstruction is possible even when the noise amplitude is larger than the signal amplitude on individual transducers. We find that a 4μ s Gaussian proton pulse can generate a signal in the range of MHz as long as the spatial heating function has sufficiently high temperature gradients.

Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA–chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light. Nile Blue (NB) is a biocompatible solvatochromic NIR dye that serves as an imaging agent. Laser irradiation of IR-780 dye leads to a temperature rise and the generation of reactive oxygen species (ROS). Resonance energy transfer between two dyes allows visualization of tumors in a wide range of visible and IR wavelengths. The combination of two NIR dyes enables the use of nanoparticles for diagnostics only or theranostics. Modification of poly(lactic-co-glycolic acid) (PLGA)–chitosan nanoparticles with trastuzumab provides an efficient nanoparticle uptake by tumor cells and promotes more than sixfold specificity towards HER2-positive cells, leading to a synergistic anticancer effect. We demonstrate optical imaging of the HER2-positive mouse mammary tumor and tumor-specific accumulation of PLGA–IR-780–NB nanoparticles in vivo after intravenous administration. We managed to achieve almost complete suppression of the proliferative activity of cells in vitro by irradiation with an 808 nm laser with a power of 0.27 W for 1 min at a concentration at which nanoparticles are nontoxic to cells in the dark. [ABSTRACT FROM AUTHOR]

Peripheral arterial diseases are commonly managed with endovascular procedures, which often face limitations in device control and visualization under X-ray fluoroscopy guidance. In response, we developed the CathCam, an angioscope integrated into an expandable cable-driven parallel mechanism to enhance real-time visualization, precise device positioning and catheter support for successful plaque crossing. The primary objective of this study was to assess and compare the performance of the novel CathCam with respect to conventional catheters and the CathPilot (i.e., CathCam without the angioscope), for applications in crossing chronic total occlusions (CTO). We first assessed the system in 3D-printed phantom models, followed by an ex vivo evaluation with CTO samples from a patient's superficial femoral artery. We measured and compared success rates, crossing times, and fluoroscopy times in both experiments. The CathCam demonstrated a 100% success rate in phantom experiments and a 75% success rate in ex vivo experiments with CTO samples, compared to conventional catheters, with 35% and 25% success rates, respectively. The average crossing times for the CathCam and the conventional catheter were 31 s and 502 s for the phantom experiments and 210 s and 511 s for the actual CTO lesions. The Cathcam also showed to be a reliable endovascular imaging approach in an in vivo experiment. Compared to conventional catheters, the CathCam significantly increased the success rate and reduced crossing and fluoroscopy times in both phantom and ex vivo setups. CathCam can potentially improve clinical outcomes for minimally invasive endovascular interventions by offering high-resolution real-time imaging alongside accurate device control. [ABSTRACT FROM AUTHOR]

Abstract Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)–PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application. Graphical Abstract

Abstract Background Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) files of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. Results The photothermal conversion efficiency of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17 °C observed at the hottest point on the surface of the tumor-bearing mice for 300 s of laser exposure at a power density of 1.4 W/cm2. Furthermore, the highest level of tissue damage, with a maximum value of Ω = 0.4, was observed in the IT injection group, as determined through a simulation study. Conclusions Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further refinement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning.

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) organic small molecule dyes (OSMDs) are effective photothermal agents for photothermal therapy (PTT) due to their advantages of low cost and toxicity, good biodegradation, and strong NIR absorption over a wide wavelength range. Nevertheless, OSMDs have limited applicability in PTT due to their low photothermal conversion efficiency and inadequate destruction of tumor regions that are nonirradiated by NIR light. However, they can also act as photosensitizers (PSs) to produce reactive oxygen species (ROS), which can be further eradicated by using ROS-related therapies to address the above limitations of PTT. In this review, the synergistic mechanism, composition, and properties of photodynamic therapy (PDT)–PTT nanoplatforms were comprehensively discussed. In addition, some specific strategies for further improving the combined PTT and PDT based on OSMDs for cancer to completely eradicate cancer cells were outlined. These strategies include performing image-guided co-therapy, enhancing tumor infiltration, increasing H2O2 or O2 in the tumor microenvironment, and loading anticancer drugs onto nanoplatforms to enable combined therapy with phototherapy and chemotherapy. Meanwhile, the intriguing prospects and challenges of this treatment modality were also summarized with a focus on the future trends of its clinical application. [ABSTRACT FROM AUTHOR]

Background: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. Methods: This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods. The model was based on Pennes' bio-heat equation and utilized a geometrically correct mice whole-body. CT26 colon tumor-bearing BALB/c mice were injected with nanohybrids and imaged using MRI (3 Tesla) before and after injection. MR images were segmented, and STereoLithography (STL) files of mice bodies and nanohybrid distribution in the tumor were established to create a realistic geometry for the model. The accuracy of the temperature predictions was validated by using an infrared (IR) camera. Results: The photothermal conversion efficiency of the nanohybrids was experimentally determined to be approximately 30%. The intratumoral (IT) injection group showed the highest temperature increase, with a maximum of 17 °C observed at the hottest point on the surface of the tumor-bearing mice for 300 s of laser exposure at a power density of 1.4 W/cm2. Furthermore, the highest level of tissue damage, with a maximum value of Ω = 0.4, was observed in the IT injection group, as determined through a simulation study. Conclusions: Our synthesized nanohybrid shows potential as an effective agent for MRI-guided NPTT. The developed model accurately predicted temperature distributions and tissue damage in the tumor. However, the current temperature validation method, which relies on limited 2D measurements, may be too lenient. Further refinement is necessary to improve validation. Nevertheless, the presented FEM model holds great promise for clinical NPTT treatment planning. [ABSTRACT FROM AUTHOR]

Multifunctional phototheranostics that integrate several diagnostic and therapeutic strategies into one platform hold great promise for precision medicine. However, it is really difficult for one molecule to possess multimodality optical imaging and therapy properties that all functions are in the optimized mode because the absorbed photoenergy is fixed. Herein, a smart one‐for‐all nanoagent that the photophysical energy transformation processes can be facilely tuned by external light stimuli is developed for precise multifunctional image‐guided therapy. A dithienylethene‐based molecule is designed and synthesized because it has two light‐switchable forms. In the ring‐closed form, most of the absorbed energy dissipates via nonradiative thermal deactivation for photoacoustic (PA) imaging. In the ring‐open form, the molecule possesses obvious aggregation‐induced emission features with excellent fluorescence and photodynamic therapy properties. In vivo experiments demonstrate that preoperative PA and fluorescence imaging help to delineate tumors in a high‐contrast manner, and intraoperative fluorescence imaging is able to sensitively detect tiny residual tumors. Furthermore, the nanoagent can induce immunogenic cell death to elicit antitumor immunity and significantly suppress solid tumors. This work develops a smart one‐for‐all agent that the photophysical energy transformation and related phototheranostic properties can be optimized by light‐driven structure switch, which is promising for multifunctional biomedical applications. [ABSTRACT FROM AUTHOR]

Microwave ablation (MWA) is becoming an increasingly important minimally invasive treatment option for localized tumors in many organ systems due to recent advancements in microwave technology that have conferred many advantages over other tumor ablation modalities. Despite these improvements in technology and development of applicators for site-specific tumor applications, the vast majority of commercially available MWA applicators are generally designed to create large-volume, symmetric, ellipsoid or spherically-shaped treatment zones and often lack the consistency, predictability, and spatial control needed to treat tumor targets near critical structures that are vulnerable to inadvertent thermal injury. The relatively new development and ongoing translation of directional microwave ablation (DMWA) technology, however, has the potential to confer an added level of control over the treatment zone shape relative to applicator position, and shows great promise to expand MWA’s clinical applicability in treating tumors in challenging locations. This paper presents a review of the industry-standard commercially available MWA technology, its clinical applications, and its limitations when used for minimally-invasive tumor treatment in medical practice followed by discussion of new advancements in experimental directional microwave ablation (DMWA) technology, various techniques and approaches to its use, and examples of how this technology may be used to treat tumors in challenging locations that may otherwise preclude safe treatment by conventional omni-directional MWA devices.

Abstract Molecular imaging technologies are increasingly used to diagnose, monitor, and guide treatment of i.e., cancer. In this review, the current status and future prospects of the use of molecular imaging as an instrument to help realize precision surgery is addressed with focus on the main components that form the conceptual basis of intraoperative molecular imaging. Paramount for successful interventions is the relevance and accessibility of surgical targets. In addition, selection of the correct combination of imaging agents and modalities is critical to visualize both microscopic and bulk disease sites with high affinity and specificity. In this context developments within engineering/imaging physics continue to drive the growth of image-guided surgery. Particularly important herein is enhancement of sensitivity through improved contrast and spatial resolution, features that are critical if sites of cancer involvement are not to be overlooked during surgery. By facilitating the connection between surgical planning and surgical execution, digital surgery technologies such as computer-aided visualization nicely complement these technologies. The complexity of image guidance, combined with the plurality of technologies that are becoming available, also drives the need for evaluation mechanisms that can objectively score the impact that technologies exert on the performance of healthcare professionals and outcome improvement for patients.

This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU. [ABSTRACT FROM AUTHOR]

Background: The medical technical innovations over the last decade have made operations in the highly sensitive regions of the brain much safer. Objective: Presentation of how far computer assistance and robotics have become incorporated into clinical neurosurgery. Material and method: Evaluation of the scientific literature and analysis of the certification status of the corresponding medical devices. Results: The rapid development of computer technology and the switch to digital imaging has led to the widespread introduction of neurosurgical planning software and intraoperative neuronavigation. In the field of robotics, the penetration into clinical neurosurgery is currently still largely limited to the automatic setting of trajectories. Conclusion: The digitalization of imaging has fundamentally transformed neurosurgery. In the field of cranial neurosurgery, computer-assisted procedures can now be distinguished from noncomputer-assisted procedures only in a handful of cases. In the coming years important innovations for the clinical implementation can be expected in the field of robotics. [ABSTRACT FROM AUTHOR]

Phantoms are physical models that mimic biological tissue and its properties in medical imaging. They play an important role in medical quality assurance, research, education, and training, since they can offer an adequate test environment. As the use of medical imaging modalities is a growing field in medicine phantoms are likewise evolving very rapidly. The variety of these phantoms is as wide as the modalities and applications, thus ranging from simple to highly detailed in the representation of anatomy. The objective of this paper is to propose a categorization of the objects defined under the term "phantom" in the literature, to reduce the misuse of this term and maintain a common understanding of the topic as well as ensure that future research efforts are based on solid foundations. This field of expertise is driven by the connection between engineering design and the field of medical technology since engineers are essential in the development of phantoms and require a clear understanding of terminology and applications. Based on a literature analysis a novel classification into distinct categories for phantoms, consisting of possible purposes, applications, manufacturing techniques, and custom design features, is developed. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850–920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging. [ABSTRACT FROM AUTHOR]

A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Dox is covalently linked with photoacoustic methylene blue (MB) to monitor Dox before, during, and after release from the hydrogel carrier. The conjugate (MB‐Dox) possesses an IC50 of 161.4 × 10−9 m against human ovarian carcinoma (SKOV3) cells and loads into a DNA‐clad hydrogel with 91.3% loading efficiency due to MB‐Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB‐Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real‐time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox. [ABSTRACT FROM AUTHOR]

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) is a type of cancer treatment capable of damaging tumors using laser irradiation. This procedure can be a promising approach to complement current cancer therapies, due in part to its minimal invasiveness. One of the challenges of photothermal therapy is the potential collateral damage to the surrounding healthy tissue, as well as excessive temperature increase in the target tumor region that can cause tissue carbonization and evaporation. With the aim of increasing the performance of photothermal therapy in damaging targeted tumor while keeping healthy nearby tissue unaffected, this research proposes the use of a feedback control system that considers the cumulative thermal damage to both types of tissue. Two separate control algorithms (fuzzy logic and PI) were designed and tested in silico using simulations made in MATLAB® and Python. Results showed that both controllers successfully accomplished the proposed goals. Therefore, the feasibility of using these automated systems to improve the efficacy and safety of PTT was demonstrated. [ABSTRACT FROM AUTHOR]

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers.

Abstract A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Dox is covalently linked with photoacoustic methylene blue (MB) to monitor Dox before, during, and after release from the hydrogel carrier. The conjugate (MB‐Dox) possesses an IC50 of 161.4 × 10−9 m against human ovarian carcinoma (SKOV3) cells and loads into a DNA‐clad hydrogel with 91.3% loading efficiency due to MB‐Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB‐Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real‐time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox.

Recently, robots have assisted and contributed to the biomedical field. Scaling down the size of robots to micro/nanoscale can increase the accuracy of targeted medications and decrease the danger of invasive operations in human surgery. Inspired by the motion pattern and collective behaviors of the tiny biological motors in nature, various kinds of sophisticated and programmable microrobots are fabricated with the ability for cargo delivery, bio-imaging, precise operation, etc. In this review, four types of propulsion—magnetically, acoustically, chemically/optically and hybrid driven—and their corresponding features have been outlined and categorized. In particular, the locomotion of these micro/nanorobots, as well as the requirement of biocompatibility, transportation efficiency, and controllable motion for applications in the complex human body environment should be considered. We discuss applications of different propulsion mechanisms in the biomedical field, list their individual benefits, and suggest their potential growth paths. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility, efficacy, and safety of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) as an alternative local treatment for extra-abdominal desmoid tumors (DTs). Methods: Eleven adult female patients (mean age = 40.1 years) with symptomatic, progressively enlarging extra-abdominal DTs were determined ineligible for cryoablation after failing observation or systemic therapy and treated with a single session doxorubicin DEB-TACE. Six rectus sheath, one chest wall, three axilla, and one upper extremity DTs were included. The median follow-up was 155.0 ± 52.3 days. Treatment response was assessed by MRIs and maximum visual analog scale (VAS). Results: All procedures were technically successful without immediate complications. The average size of treated DT was 161.8 ml (range: 28.3–420.0 ml). The mean doxorubicin dose was 13.3 mg/m2. All patients experienced skin changes which improved over time without treatments. No higher-grade adverse events were observed. Initial one-month follow-up MRI demonstrated partial to near-complete tumor necrosis, ranging from 1.4 to 97.6% (mean: 36.4%). Additional follow-up revealed a further reduction of overall tumor volume (mean: − 38.1%, p < 0.0001) and maximum VAS (mean: − 2.6, p = 0.0026) in 10 out of 11 patients (90.9%). After the first month, the residual tumors exhibited continued volume reduction in 10 out of 11 patients (mean: − 16.5%, p = 0.0230). There was also a significant decrease of T2 signal intensity within residual tumor on the latest follow-up (mean: − 29.6%, p = 0.0217), suggesting a reduction in tumor cellularity. Conclusion: DEB-TACE may be a safe and effective local treatment alternative in DT patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Focused ultrasound (FUS) and microbubble (MB) exposure is a promising technique for targeted drug delivery to the brain; however, refinement of protocols suitable for large-volume treatments in a clinical setting remains underexplored. Methods: Here, the impacts of various sonication parameters on blood-brain barrier (BBB) permeability enhancement and tissue damage were explored in rabbits using a clinical-prototype hemispherical phased array developed in-house, with real-time 3D MB cavitation imaging for exposure calibration. Initial experiments revealed that continuous manual agitation of MBs during infusion resulted in greater gadolinium (Gd) extravasation compared to gravity drip infusion. Subsequent experiments used low-dose MB infusion with continuous agitation and a low burst repetition frequency (0.2 Hz) to mimic conditions amenable to long-duration clinical treatments. Results: Key sonication parameters-target level (proportional to peak negative pressure), number of bursts, and burst length-significantly affected BBB permeability enhancement, with all parameters displaying a positive relationship with relative Gd contrast enhancement ( p < 0.01). Even at high levels of BBB permeability enhancement, tissue damage was minimal, with low occurrences of hypointensities on T2*-weighted MRI. When accounting for relative Gd contrast enhancement, burst length had a significant impact on red blood cell extravasation detected in histological sections, with 1 ms bursts producing significantly greater levels compared to 10 ms bursts ( p = 0.03), potentially due to the higher pressure levels required to generate equal levels of BBB permeability enhancement. Additionally, albumin and IgG extravasation correlated strongly with relative Gd contrast enhancement across sonication parameters, suggesting that protein extravasation can be predicted from non-invasive imaging. Conclusions: These findings contribute to the development of safer and more effective clinical protocols for FUS + MB exposure, potentially improving the efficacy of the approach.

Breast cancer remains a leading cause of morbidity and mortality among women worldwide. Early detection and precise diagnosis are critical for effective treatment and improved patient outcomes. This review explores the evolving role of radiology in the diagnosis and treatment of breast cancer, highlighting advancements in imaging technologies and the integration of artificial intelligence (AI). Traditional imaging modalities such as mammography, ultrasound, and magnetic resonance imaging have been the cornerstone of breast cancer diagnostics, with each modality offering unique advantages. The advent of radiomics, which involves extracting quantitative data from medical images, has further augmented the diagnostic capabilities of these modalities. AI, particularly deep learning algorithms, has shown potential in improving diagnostic accuracy and reducing observer variability across imaging modalities. AI-driven tools are increasingly being integrated into clinical workflows to assist in image interpretation, lesion classification, and treatment planning. Additionally, radiology plays a crucial role in guiding treatment decisions, particularly in the context of image-guided radiotherapy and monitoring response to neoadjuvant chemotherapy. The review also discusses the emerging field of theranostics, where diagnostic imaging is combined with therapeutic interventions to provide personalized cancer care. Despite these advancements, challenges such as the need for large annotated datasets and the integration of AI into clinical practice remain. The review concludes that while the role of radiology in breast cancer management is rapidly evolving, further research is required to fully realize the potential of these technologies in improving patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arslan et al.)

Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.

Developing image-guided robotic systems requires access to flexible, open-source software. For image guidance, the open-source medical imaging platform 3D Slicer is one of the most adopted tools that can be used for research and prototyping. Similarly, for robotics, the open-source middleware suite robot operating system (ROS) is the standard development framework. In the past, there have been several "ad hoc" attempts made to bridge both tools; however, they are all reliant on middleware and custom interfaces. Additionally, none of these attempts have been successful in bridging access to the full suite of tools provided by ROS or 3D Slicer. Therefore, in this paper, we present the SlicerROS2 module, which was designed for the direct use of ROS2 packages and libraries within 3D Slicer. The module was developed to enable real-time visualization of robots, accommodate different robot configurations, and facilitate data transfer in both directions (between ROS and Slicer). We demonstrate the system on multiple robots with different configurations, evaluate the system performance and discuss an image-guided robotic intervention that can be prototyped with this module. This module can serve as a starting point for clinical system development that reduces the need for custom interfaces and time-intensive platform setup. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging using energy conversion from light to ultrasound waves has been developed as a powerful tool to investigate in vivo phenomena due to their complex characteristics. In photoacoustic imaging, endogenous chromophores such as oxygenated hemoglobin, deoxygenated hemoglobin, melanin, and lipid provide useful biomedical information at the molecular level. However, these intrinsic absorbers show strong absorbance only in visible or infrared optical windows and have limited light transmission, making them difficult to apply for clinical translation. Therefore, the development of novel exogenous contrast agents capable of increasing imaging depth while ensuring strong light absorption is required. We report here the application of carbon nanomaterials that exhibit unique physical, mechanical, and electrochemical properties as imaging probes in photoacoustic imaging. Classified into specific structures, carbon nanomaterials are synthesized with different substances according to the imaging purposes to modulate the absorption spectra and highly enhance photoacoustic signals. In addition, functional drugs can be loaded into the carbon nanomaterials composite, and effective in vivo monitoring and photothermal therapy can be performed with cell-specific targeting. Diverse applied cases suggest the high potential of carbon nanomaterial-based photoacoustic imaging in in vivo monitoring for clinical research. [ABSTRACT FROM AUTHOR]

Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome. [ABSTRACT FROM AUTHOR]

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

The role of retinal photocoagulation as a first line therapy for various retinal pathologies has decreased with the introduction of anti-vascular endothelial growth factor therapy. However, retinal laser therapy remains an important treatment modality, especially with the emergence of micropulse subthreshold treatment and the integration of newer technology such as augmented reality and semi-automated delivery. This review summarizes current evidence for micropulse laser as a treatment modality and discusses the role of new technology such as augmented reality in the future of laser therapy.

PurposeTo demonstrate the use of anatomic MRI-visible three-dimensional (3D)-printed phantoms and to assess process accuracy and material MR signal properties.MethodsA cervical spine model was generated from computed tomography (CT) data and 3D-printed using an MR signal-generating material. Printed phantom accuracy and signal characteristics were assessed using 120 kVp CT and 3 Tesla (T) MR imaging. The MR relaxation rates and diffusion coefficient of the fabricated phantom were measured and 1 H spectra were acquired to provide insight into the nature of the proton signal. Finally, T2 -weighted imaging was performed during cryoablation of the model.ResultsThe printed model produced a CT signal of 102 ± 8 Hounsfield unit, and an MR signal roughly 1/3rd that of saline in short echo time/short repetition time GRE MRI (456 ± 36 versus 1526 ± 121 arbitrary signal units). Compared with the model designed from the in vivo CT scan, the printed model differed by 0.13 ± 0.11 mm in CT, and 0.62 ± 0.28 mm in MR. The printed material had T2 ∼32 ms, T2*∼7 ms, T1 ∼193 ms, and a very small diffusion coefficient less than olive oil. MRI monitoring of the cryoablation demonstrated iceball formation similar to an in vivo procedure.ConclusionCurrent 3D printing technology can be used to print anatomically accurate phantoms that can be imaged by both CT and MRI. Such models can be used to simulate MRI-guided interventions such as cryosurgeries. Future development of the proposed technique can potentially lead to printed models that depict different tissues and anatomical structures with different MR signal characteristics. Magn Reson Med 77:613-622, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

ObjectivesUltrasound-guided percutaneous nephrolithotomy (PCNL) has become increasingly utilized. Patients with nondilated collecting systems represent a challenge: the target calix is often difficult to visualize. Here we report pilot study results for retrograde ultrasound contrast injection to aid in percutaneous renal access during ultrasound-guided PCNL.Patients and methodsFrom April to July 2016, consecutive patients over the age of 18 years with nondilated collecting systems on preoperative imaging who presented for PCNL were enrolled. B-mode ultrasound imaging was compared with contrast-enhanced mode with simultaneous retrograde injection of Optison™ via an ipsilateral ureteral catheter.ResultsFive patients (four males and one female) with renal stones underwent PCNL with retrograde ultrasound contrast injection during the study period. Mean body mass index was 28.3 ± 5.6 kg/m2 and mean stone size was 24.5 ± 12.0 mm. Under B-mode ultrasound, all patients demonstrated nondilated renal collecting systems that appeared as hyperechoic areas, where it was difficult to identify a target calix for puncture. Retrograde contrast injection facilitated delineation of all renal calices initially difficult to visualize under B-mode ultrasound. Renal puncture was then performed effectively in all cases with a mean puncture time of 55.4 ± 44.8 seconds. All PCNL procedures were completed without intraoperative complications and no adverse events related to ultrasound contrast injection occurred.ConclusionRetrograde ultrasound contrast injection as an aide for renal puncture during PCNL is a feasible technique. By improving visualization of the collecting system, it facilitates needle placement in challenging patients without hydronephrosis. Future larger scale studies comparing its use to standard ultrasound-guided technique will be required to validate this concept.

This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU.

Minimally invasive image-guided interventions have changed the face of procedural medicine. For these procedures, safety and efficacy depend on precise needle placement. Needle targeting devices help improve the accuracy of needle placement, but their use has not seen broad penetration. Some of these devices are costly and require major modifications to the clinical workflow. In this article, we developed a low-cost, disposable, and easy-to-use angulation tracking device, which was based on a redesigned commercial passive needle holder. The new design provided real-time angulation information for needle tracking. In this design, two potentiometers were used as angulation sensors, and they were connected to two axes of the passive needle holder's arch structure through a 3 D-printed bridge structure. A control unit included an Arduino Pro Mini, a Bluetooth module, and two rechargeable batteries. The angulation was calculated and communicated in real time to a novel developed smartphone app, where real-time angulation information was displayed for guiding the operator to position the needle to the planned angles. The open-air test results showed that the average errors are 1.03° and 1.08° for left–right angulation and head–foot angulation, respectively. The animal cadaver tests revealed that the novel system had an average angular error of 3.2° and a radial distance error of 3.1 mm. The accuracy was comparable with some commercially available solutions. The novel and low-cost needle tracking device may find a role as part of a real-time precision approach to both planning and implementation of image-guided therapies. [ABSTRACT FROM AUTHOR]

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Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1–4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications. An ultralow fouling NIR-II probe HLA4P self-assembled into micelles with long-circulation persistence and ultrahigh signal-background ratio for routine preoperative tumor assessment and trackable drug delivery. [Display omitted] • A new TTD-based NIR-II dye (HLA4P) with a high fluorescence QY, exceptional nonfouling performance and low immunogenicity. • HLA4P exhibited ultralong blood circulation, super-contrast ratio and long tumor retention by various injection routes. • HLA4P could be simultaneously used for long-term in vivo NIR-II tracking of drug delivery and therapy. • HLA4P@DOX showed sustained DOX release behavior, enhanced therapeutic effect and diminished toxicity. [ABSTRACT FROM AUTHOR]