Cancer Therapy Monitoring Research Articles

Abstract B033: Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring

Abstract The advancement of liquid biopsy techniques promises to revolutionize cancer diagnostics and therapy monitoring, by offering a minimally invasive approach to track tumor progression and treatment efficacy. One central issue preventing advancements are innovations in sensor technology, necessary to enable the detection of molecular and cellular biomarkers with sufficient precision. Over the past decade, atomic-scale quantum sensors have emerged as powerful detectors, offering the ability to perform precise measurements of temperature, pressure, and magnetic fields on the single cell scale. These sensors, based on the interaction of spin qubits with their environment, have the unique capability to amplify and exploit environmental interactions for highly accurate detection, making them ideal for complex biological applications. In this context, we present an advanced quantum sensing platform specifically tailored for liquid biopsy applications in cancer therapy monitoring. This platform integrates the capabilities of optical microscopy with magnetic resonance imaging (MRI) techniques, utilizing nitrogen-vacancy (NV) centers in diamond as quantum sensors by converting magnetic resonance signals into optical signals, which are subsequently captured by a high-speed camera. Our platform offers a novel approach, promising quantitative analysis of single cancer cells from liquid samples with unprecedented accuracy. Unlike traditional MRI, our method captures signals over a wide field of view directly in real space. Each camera pixel records a magnetic resonance spectrum, providing detailed multicomponent information about the sample, such as molecular concentration, diffusion, and relaxation behavior, which are critical for understanding the tumor’s microenvironment. Our quantum sensing technology holds significant potential for enhancing the sensitivity of liquid biopsies. By capturing detailed molecular information from blood or other body fluids, it will enable in-depth analysis of Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other biomarkers. Citation Format: Karl D. Briegel, Robin D. Allert, Dominik B. Bucher, Julia D. Draeger, Nick R v. Grafenstein, Linyan Nie. Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B033.

Smartphone-based lateral flow immunoassay for sensitive determination of lactate dehydrogenase at the point of care

Lactate dehydrogenase (LDH), a prevalent enzyme involved in anaerobic glycolysis, is released into body fluids following cell damage and has long been a general marker of tissue injury. However, due to its lack of selectivity and the advent of more accurate biomarkers, the clinical utility of LDH has been largely limited to confirming hemolysis. LDH has been recognized as a valuable prognostic biomarker for various cancers, making its monitoring crucial during cancer management. Traditional LDH methods include spectrophotometric analysis of NADH at 340 nm, native electrophoresis, or enzyme-linked immunosorbent assay. This study presents the first lateral flow immunoassay (LFIA) for the smartphone-based quantification of serum LDH levels at the point of care. Highly-affinity and specific antibodies have been produced, with 5 nM equilibrium dissociation constant and no cross-reactivity with human serum albumin and human immunoglobulin G. Utilizing carbon nanoparticles as signal transducers significantly enhanced the quantification limit 55-fold, compared to the conventional gold nanoparticles-based LFIA, achieving a quantification limit of 1.5 ng mL−1. The developed assay demonstrated a mean recovery rate of 115 ± 21 % when evaluating LDH-spiked serum samples. This method can be an interesting home-testing tool for monitoring cancer progression or therapy effectiveness.

Clinical Utility of Global Longitudinal Strain in Cancer Therapy Monitoring

Clinical Utility of Global Longitudinal Strain in Cancer Therapy Monitoring

BIOM-09. TOWARDS CLINICAL IMPLEMENTATION OF LIQUID BIOPSY ANALYSIS FOR PAEDIATRIC BRAIN TUMOUR PATIENTS – A PAN-EUROPEAN EFFORT FOR STANDARDIZATION

Abstract BACKGROUND Liquid biopsies (LBs) allow for analysis of tumour-derived molecules, such as cell-free DNA (cfDNA) and microRNAs (miRNAs), complementing cancer diagnostics, therapy monitoring, and minimal residual disease detection. While circulation-based LB has benefit for extracranial tumour entities, peripheral blood has not historically been a reliable source for diagnosis and disease-monitoring in brain tumours. For these tumours, cerebrospinal fluid (CSF) analysis is better suited for detection despite being a more invasive procedure. However, standardized protocols for sample collection and pre-analytical parameters for these LBs currently are limited. AIM We aim to establish an evidence-based gold standard protocol for cfDNA and miRNA analyses from CSF in paediatric brain tumour patients. In addition to higher compliance in trial-related CSF sampling, this initiative seeks to facilitate identification of clinically relevant indications and time-points for collection, thereby paving the way for well-informed, routine CSF molecular diagnostics. METHODS AND RESULTS We have initiated the Liquid Biopsy Working Group within the framework of the International Society of Paediatric Oncology Europe Brain Tumour Group (SIOPE-BTG). Available literature on LB in brain tumours was critically assessed regarding pre-analytical parameters, downstream analyses and LB assay performance. To directly evaluate confounding by pre-analytical factors, we experimentally compared the impact of CSF sampling sites, storage conditions, and different pre-processing protocols. cfDNA and miRNA yields, purity, and the fraction of tumour-derived material were selected as read-outs and correlated with tumour tissue information. To prepare for clinical translation, we consulted clinical paediatric brain tumour trial coordinators to identify major bottlenecks for CSF sampling in routine clinical practice. In addition, clinical practitioners and patient/ parent representatives have been consulted to comprehensively represent the perspectives and needs of all stakeholders. Together, results of this collaborative effort will be fundamental to the successful clinical integration of LBs to improve the future management of paediatric brain tumour patients.

Towards clinical adherence monitoring of oral endocrine breast cancer therapies by LC-HRMS—method development, validation, comparison of four sample matrices, and proof of concept

Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients’ caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations.Graphical

Combinations of plasma cfDNA concentration, integrity and tumor markers are promising biomarkers for early diagnosis of non-small cell lung cancer

BackgroundCirculating cell-free DNA (cfDNA) concentration and integrity as noninvasive biomarkers play an important role in cancer diagnosis, prognosis and therapy monitoring. However, few studies have been conducted on the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) for cancer detection. Thus, the purpose of this study was to investigate the diagnostic value of combining plasma cfDNA concentration, integrity and tumor markers in early detection of non-small cell lung cancer (NSCLC). MethodsPlasma cfDNA concentration from 50 healthy controls and 84 NSCLC patients were assessed by quantitative real-time PCR of ALU repeated sequence. Plasma cfDNA integrity was calculated as the ratio of long to short fragments (ALU115/60). ResultsPlasma cfDNA concentration (ALU60 and ALU115) and integrity ALU115/60 were significantly higher in NSCLC patients with stage III/IV than in healthy controls (p = 0.0002, p < 0.0001, and p = 0.0093, respectively). The receiver operating characteristic (ROC) curve for discriminating NSCLC patients from healthy controls had an area under the curve (AUC) of 0.936 (95 % CI, 0.939–0.996). Moreover, the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) had higher diagnostic performance than either plasma cfDNA concentration alone, integrity alone or tumor markers alone, with sensitivity, specificity and AUC value of 94.05%, 90.00% and 0.968, respectively. These results demonstrated that the combination of plasma cfDNA concentration, integrity and tumor markers could significantly improve the diagnostic accuracy of NSCLC. ConclusionCombination of plasma cfDNA concentration, integrity and tumor markers is a promising biomarker for early diagnosis of NSCLC.

The accuracy of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of ovarian cancer relapse in patients with rising cancer antigen 125 (CA-125) levels

Background18F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive imaging tool that has been used successfully for the diagnosis, staging, restaging, therapy monitoring, and prognostic prediction of ovarian cancer. For ovarian cancer surveillance, rising CA-125 levels raise the suspicion of recurrence despite its reported low specificity; being elevated in other benign and inflammatory conditions, and thus, confirmation is required. This work aimed to evaluate the role of 18F-FDG PET/CT in suspected ovarian cancer recurrence in patients presenting with elevated CA-125 levels.ResultsFifty female patients with suspected ovarian cancer recurrence owing to elevated CA-125 levels were included in this study. Recurrence was confirmed in 46/50 cases whether by histopathological confirmation or by serial follow-up imaging and clinical follow-up. Positive PET/CT findings were reported in 45/50 cases with 2 false-negative cases and 1 false-positive case. PET/CT examination was found to be superior to contrast-enhanced CT in the detection of peritoneal metastatic nodules and metastatic lymph nodes. According to this study, the estimated sensitivity, specificity, and overall diagnostic accuracy of PET/CT in the detection of recurrent ovarian cancer were 95.6%, 75%, and 94%, respectively.ConclusionsIn ovarian cancer surveillance, 18F-FDG PET/CT was found to be a sensitive and accurate noninvasive imaging tool that can be used in the detection of recurrent ovarian cancer in patients with elevated CA-125 levels, thus interfering with the management plan. The advantage of whole-body imaging in PET/CT allows for the detection and precise localization of recurrent or metastatic foci in abdominal and extra-abdominal sites as well.

Fully implantable and battery-free wireless optoelectronic system for modulable cancer therapy and real-time monitoring

Photodynamic therapy (PDT) is attracting attention as a next-generation cancer treatment that can selectively destroy malignant tissues, exhibit fewer side effects, and lack pain during treatments. Implantable PDT systems have recently been developed to resolve the issues of bulky and expensive conventional PDT systems and to implement continuous and repetitive treatment. Existing implantable PDT systems, however, are not able to perform multiple functions simultaneously, such as modulating light intensity, measuring, and transmitting tumor-related data, resulting in the complexity of cancer treatment. Here, we introduce a flexible and fully implantable wireless optoelectronic system capable of continuous and effective cancer treatment by fusing PDT and hyperthermia and enabling tumor size monitoring in real-time. This system exploits micro inorganic light-emitting diodes (μ-LED) that emit light with a wavelength of 624 nm, designed not to affect surrounding normal tissues by utilizing a fully programmable light intensity of μ-LED and precisely monitoring the tumor size by Si phototransistor during a long-term implantation (2–3 weeks). The superiority of simultaneous cancer treatment and tumor size monitoring capabilities of our system operated by wireless power and data transmissions with a cell phone was confirmed through in vitro experiments, ray-tracing simulation results, and a tumor xenograft mouse model in vivo. This all-in-one single system for cancer treatment offers opportunities to not only enable effective treatment of tumors located deep in the tissue but also enable precise and continuous monitoring of tumor size in real-time.

Chlorambucil combined with a fluorophore for targeted cancer therapy and real-time monitoring of cancer cell death

The clinical applications of chlorambucil are limited by poor cellular permeability, lack of targeting, and severe side effects. In this study, a novel fluorophore-drug conjugate using chlorambucil as a model anticancer agent and 1,8-naphthalimide derivatives as the parent fluorophore was constructed. This novel fluorophore-drug conjugate could maintain a high concentration and high toxicity of drug in cancer cells by targeting lipid droplets. Cell imaging showed that the constructed novel fluorophore-drug conjugate exhibited a good cell uptake ability. Furthermore, the fluorophore component of conjugate acted as a fluorescent dye that emitted measurable signal when interacting with cancer cells. Therefore, fluorophore-drug conjugate showed the potential to be used for monitoring drug biodistribution in vivo in real time, which was of great significance in studying the mechanism of action of anticancer agents. Finally, we estimated of cancer cell death by monitoring the decrease in the number of lipid droplets and the increase in cell polarity. In conclusion, a novel fluorophore-drug conjugate with high cancer cell toxicity and capable of real-time monitoring of cancer cell survival status was successfully developed,opening up new possibilities for cancer therapy and diagnosis.

A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer.

Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC. CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo. Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2β, and AUC0-t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment. Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.

Advances in liquid biopsy-based markers in NSCLC.

Lung cancer is the second most-frequently occurring cancer and the leading cause of cancer-associated deaths worldwide. Non-small cell lung cancer (NSCLC), the most common type of lung cancer is often diagnosed in middle or advanced stages and have poor prognosis. Diagnosis of disease at an early stage is a key factor for improving prognosis and reducing mortality, whereas, the currently used diagnostic tools are not sufficiently sensitive for early-stage NSCLC. The emergence of liquid biopsy has ushered in a new era of diagnosis and management of cancers, including NSCLC, since analysis of circulating tumor-derived components, such as cell-free DNA (cfDNA), circulating tumor cells (CTCs), cell-free RNAs (cfRNAs), exosomes, tumor-educated platelets (TEPs), proteins, and metabolites in blood or other biofluids can enable early cancer detection, treatment selection, therapy monitoring and prognosis assessment. There have been great advances in liquid biopsy of NSCLC in the past few years. Hence, this chapter introduces the latest advances on the clinical application of cfDNA, CTCs, cfRNAs and exosomes, with a particular focus on their application as early markers in the diagnosis, treatment and prognosis of NSCLC.

An erythrocyte membrane-modified biomimetic synergistic nanosystem for cancer anti-vascular therapy and initial efficacy monitoring.

Tumor vascular disruption has become a promising strategy for cancer therapy in recent decades. Nanocomposites loaded with therapeutic materials and drugs are expected to improve the accuracy of anti-vascular therapy and minimize side effects. However, how to prolong blood circulation of therapeutic nanocomposites for enhanced accumulation in tumor vasculature and how to monitor the initial efficacy of anti-vascular therapy for early evaluation of prognosis remain unsolved. Herein, a biomimetic nanosystem consisting of erythrocyte membrane modified nanocomposites (CMNCs) is developed for cooperation to achieve anti-vascular cancer therapy and initial efficacy monitoring. By utilizing poly(lactic-co-glycolic acid) (PLGA) as the interface material, functional nanomaterials and drug molecules are successfully integrated into CMNCs. The long circulation and immune escape features of the erythrocyte membrane facilitate CMNCs loaded with photothermal agents and chemodrugs to be delivered to the tumor region for anti-vascular treatment. Furthermore, the vascular damage-induced haemorrhage and the following coagulation process is labelled by near infrared emissive CMNCs to indicate the initial therapeutic efficacy of the treatment. This work not only points to a biomimetic strategy for conquering the challenges in anti-vascular cancer therapy, but also provides insights into the biological responses of erythrocyte membrane modified nanocomposites to exploit their biomedical applications.

Blood platelets as an RNA biomarker platform for neuro-oncological diseases.

Blood-based liquid biopsies are an upcoming approach for earlier cancer detection, diagnostics, prognostics, therapy-response prediction, and therapy monitoring, including in patients with tumors of the central nervous system. Among these, liquid biopsies are plasma-derived markers such as cell-free DNA, RNA and proteins, extracellular vesicles, circulating glioma cells, immune cells, and blood platelets. Blood platelets are involved in the local and systemic response to the presence of cancer, thereby sequestering and splicing RNAs, which may be clinically useful as blood-based biomarkers. In this review, we discuss the available literature regarding the role of blood platelets in gliomas and provide suggestions for future research efforts.

Nitrogen Mustard Based 2-Benzylidene-1-tetralone as ICT-Based Fluorescent Probe for Drug Release Monitoring and Cervical Cancer Therapy

Nitrogen Mustard Based 2-Benzylidene-1-tetralone as ICT-Based Fluorescent Probe for Drug Release Monitoring and Cervical Cancer Therapy

Monitoring of Current Cancer Therapy by Positron Emission Tomography and Possible Role of Radiomics Assessment.

Evaluation of cancer therapy with imaging is crucial as a surrogate marker of effectiveness and survival. The unique response patterns to therapy with immune-checkpoint inhibitors have facilitated the revision of response evaluation criteria using FDG-PET, because the immune response recalls reactive cells such as activated T-cells and macrophages, which show increased glucose metabolism and apparent progression on morphological imaging. Cellular metabolism and function are critical determinants of the viability of active cells in the tumor microenvironment, which would be novel targets of therapies, such as tumor immunity, metabolism, and genetic mutation. Considering tumor heterogeneity and variation in therapy response specific to the mechanisms of therapy, appropriate response evaluation is required. Radiomics approaches, which combine objective image features with a machine learning algorithm as well as pathologic and genetic data, have remarkably progressed over the past decade, and PET radiomics has increased quality and reliability based on the prosperous publications and standardization initiatives. PET and multimodal imaging will play a definitive role in personalized therapeutic strategies by the precise monitoring in future cancer therapy.

Designer tetrahedral DNA framework-based microfluidic technology for multivalent capture and release of circulating tumor cells.

Circulating tumor cells (CTCs) have been recognized as a general biomarker for the early detection, diagnosis and therapy monitoring of cancer. Due to their extreme rarity in peripheral blood, the isolation and analysis of CTCs with high efficiency, high purity and high viability remains a tremendous technological challenge. Herein, we combined tetrahedral DNA framework (TDFs), herringbone channel (HB) chip, together with aptamer-triggered hybridization chain reaction (apt-HCR) to develop an efficient microfluidic system (T-μFS) for capture and release of simulated CTCs. The capture efficiency of MCF-7 ​cells was from 83.3% to 94.2% when the cell numbers ranged from 10 to 103 using our T-μFS in the whole blood. The release efficiency of the MCF-7 ​cells was 96.2% and the MCF-7 ​cell viability after release was 94.6% using our T-μFS in PBS buffer. Reculture and RT-qPCR studies showed that there was almost no damage by the capture and release treatment for the MCF-7 ​cells viability. These results revealed that our T-μFS could be developed as an integrated and automatic technical platform with great performance for multivalent capture and release of CTCs and have a wide application prospect for tumor liquid biopsy.

Body Fluid Biopsy: A New Paradigm in Early Diagnosis and Success Monitoring of Colorectal Cancer Therapy

Colorectal cancer (CRC) is a type of cancer with a high prevalence of 10.2% and ranks third highest in the world with the second highest mortality rate. In Indonesia, CRC is the 4th most common type of cancer, with a prevalence of 9.88%. Up to now, the definitive diagnosis of CRC colon biopsy using a colonoscopy, which is very invasive, relatively expensive, and requires an expert to do it. Liquid biopsy is one of the breakthroughs in the field of CRC that can be used for screening and early diagnosis and assessing the prognosis and response to treatment. Liquid biopsy has advantages over tissue biopsy. Some of the materials that can be texted from a liquid biopsy are: circulating cell tumors (CTCs), cell-free DNA (cfDNA), circulating tumor RNA (ctRNA), proteins, metabolites, and exosomes. Exosomes are microvesicles that are released from tumor cells to target cells and contain a lot of cancer genetic information, such as microRNAs, lncRNAs, mRNAs and proteins. Through this article, the author would like to describe the potential of CRC test using liquid biopsy which has almost never been studied and used as a potential biomarker in Indonesia.

Current and Developing Liquid Biopsy Techniques for Breast Cancer.

Simple SummaryBreast cancer is the most common cancer and leading cause of death worldwide. Therefore, it is important to diagnose and treat breast cancer early. Current diagnostic methods include mammography and tissue biopsy; however, they have limitations. Liquid biopsy is a less invasive tool for diagnosis. In this review, we summarize and focus on the recent discoveries on liquid biopsy and development of detection techniques.Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality among woman worldwide. The techniques of diagnosis, prognosis, and therapy monitoring of breast cancer are critical. Current diagnostic techniques are mammography and tissue biopsy; however, they have limitations. With the development of novel techniques, such as personalized medicine and genetic profiling, liquid biopsy is emerging as the less invasive tool for diagnosing and monitoring breast cancer. Liquid biopsy is performed by sampling biofluids and extracting tumor components, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free mRNA (cfRNA) and microRNA (miRNA), proteins, and extracellular vehicles (EVs). In this review, we summarize and focus on the recent discoveries of tumor components and biomarkers applied in liquid biopsy and novel development of detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and microfluidic devices.

Advanced Biophotonics Techniques: The Role of Optical Tweezers for Cells and Molecules Manipulation Associated With Cancer

Rapid advances in Biophotonics are revolutionizing the illumination of several diseases and, among them, the monitoring of cancer pathogenesis and therapy. Today, several efforts aim to miniaturize the Biophotonics tools, leading to the namely Nanobiophotonics. This scientific field refer to the development of novel technologies, biosensors, and drug delivery systems for prevention, diagnosis, and treatment of diseases at the nanoscale, in sub-cellular and molecular level. Modern non-invasive laser-based techniques are applied in different domains, from practical, clinical applications to molecular and cellular biology fundamental research. Among the plethora of photon-based techniques, optical trapping is a very promising tool for improving the understanding of cancer at cellular level. Recently, optical tweezers are revived as a potential technique for cell characterization, tracking cells behavior and probing interactions forces between cells, cells-biomolecules, and cells-nanoparticles. In this review, we aim to exhibit the state-of the art advances of Biophotonics in the diagnostic and therapeutic field of cancer focusing on the role of optical tweezers.

Accelerated Digital Biodetection Using Magneto-plasmonic Nanoparticle-Coupled Photonic Resonator Absorption Microscopy.

Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection via toehold-mediated strand displacement. Spiky Fe3O4@Au MPNPs with immobilized target-specific probes are "activated" by binding with miRNA targets, followed by magnetically driven transport through the bulk fluid toward nanoparticle capture probes on a photonic crystal (PC). By spectrally matching the localized surface plasmon resonance of the MPNPs to the PC-guided resonance, each captured MPNP locally quenches the PC reflection efficiency, thus enabling captured MPNPs to be individually visualized with high contrast for counting. We demonstrate quantification of the miR-375 cancer biomarker directly from unprocessed human serum with a 1 min response time, a detection limit of 61.9 aM, a broad dynamic range (100 aM to 10 pM), and a single-base mismatch selectivity. The approach is well-suited for minimally invasive biomarker quantification, enabling potential applications in point-of-care testing with short sample-to-answer time.