A Comparative Analysis of Alpha and Beta Therapy in Prostate Cancer Using a 3D Image-Based Spatiotemporal Model.

Purpose: In treating prostate cancer, distinguishing alpha and beta therapies is vital for efficient radiopharmaceutical delivery. Our study introduces a 3D image-based spatiotemporal computational model that utilizes MRI-derived images to evaluate the efficacy of Ac-PSMA and Lu-PSMA therapies. We examine the impact of tumor size, diffusion, interstitial fluid pressure (IFP), and interstitial fluid velocity (IFV) on the absorbed doses.

Enhancing localized chemotherapy with anti-angiogenesis and nanomedicine synergy for improved tumor penetration in well-vascularized tumors.

Intratumoral delivery and localized chemotherapy have demonstrated promise in tumor treatment; however, the rapid drainage of therapeutic agents from well-vascularized tumors limits their ability to achieve maximum therapeutic efficacy. Therefore, innovative approaches are needed to enhance treatment efficacy in such tumors. This study utilizes a mathematical modeling platform to assess the efficacy of combination therapy using anti-angiogenic drugs and drug-loaded nanoparticles.

Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model.

Lutetium-177 prostate-specific membrane antigen (Lu-PSMA)-targeted radiopharmaceutical therapy is a clinically approved treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Even though common practice reluctantly follows "one size fits all" approach, medical community believes there is significant room for deeper understanding and personalization of radiopharmaceutical therapies. To pursue this aim, we present a 3-dimensional spatiotemporal radiopharmaceutical delivery model based on clinical imaging data to simulate pharmacokinetic of Lu-PSMA within the prostate tumors.

Spatiotemporal modeling of nano-delivered chemotherapeutics for synergistic microwave ablation cancer therapy.

Background And Objective: The effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved.

Effect of tumor heterogeneity on enhancing drug delivery to vascularized tumors using thermo-sensitive liposomes triggered by hyperthermia: A multi-scale and multi-physics computational model.

In this study, a novel multi-scale and multi-physics image-based computational model is introduced to assess the delivery of doxorubicin (Dox) loaded temperature-sensitive liposomes (TSLs) in the presence of hyperthermia. Unlike previous methodologies, this approach incorporates capillary network geometry extracted from images, resulting in a more realistic physiological tumor model. This model holds significant promise in advancing personalized medicine by integrating patient-specific tumor properties.

Multi-Scale and Multi-Physics Models of the Transport of Therapeutic/Diagnostic Cancer Agents.

The effectiveness of tumor treatment heavily relies on the successful delivery of anticancer drugs [...

Integrating Therapeutic Ultrasound With Nanosized Drug Delivery Systems in the Battle Against Cancer.

Controlled, localized, and timely activation of nanosized drug delivery systems (NSDDSs), using an external stimulus such as therapeutic ultrasound (TUS), can improve the efficacy of cancer treatments compared to either conventional chemotherapy methods or passive NSDDSs alone. Specifically, TUS induces thermal and mechanical effects that trigger drug release from NSDDSs and overcomes drug delivery barriers in tumor microenvironments to allow nanoparticle drug carriers to penetrate more deeply into tumor tissue while minimizing side effects. This review highlights recent advancements, contemplates future prospects, and addresses challenges in using TUS-mediated NSDDSs for cancer treatment, encompassing preclinical and clinical applications.

A comparative study between conventional chemotherapy and photothermal activated nano-sized targeted drug delivery to solid tumor.

Delivery of chemotherapeutic medicines to solid tumors is critical for optimal therapeutic success and minimal adverse effects. We mathematically developed a delivery method using thermosensitive nanocarriers activated by light irradiation. To assess its efficacy and identify critical events and parameters affecting therapeutic response, we compared this method to bolus and continuous infusions of doxorubicin for both single and multiple administrations.

Ultrasound-mediated nano-sized drug delivery systems for cancer treatment: Multi-scale and multi-physics computational modeling.

Computational modeling enables researchers to study and understand various complex biological phenomena in anticancer drug delivery systems (DDSs), especially nano-sized DDSs (NSDDSs). The combination of NSDDSs and therapeutic ultrasound (TUS), that is, focused ultrasound and low-intensity pulsed ultrasound, has made significant progress in recent years, opening many opportunities for cancer treatment. Multiple parameters require tuning and optimization to develop effective DDSs, such as NSDDSs, in which mathematical modeling can prove advantageous.

A spatiotemporal computational model of focused ultrasound heat-induced nano-sized drug delivery system in solid tumors.

Focused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach.

Stimuli-sensitive nano-drug delivery with programmable size changes to enhance accumulation of therapeutic agents in tumors.

Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced.

Ultrasound-mediated nano drug delivery for treating cancer: Fundamental physics to future directions.

The application of biocompatible nanocarriers in medicine has provided several benefits over conventional treatment methods. However, achieving high treatment efficacy and deep penetration of nanocarriers in tumor tissue is still challenging. To address this, stimuli-responsive nano-sized drug delivery systems (DDSs) are an active area of investigation in delivering anticancer drugs.

Spatiotemporal multi-scale modeling of radiopharmaceutical distributions in vascularized solid tumors.

We present comprehensive mathematical modeling of radiopharmaceutical spatiotemporal distributions within vascularized solid tumors. The novelty of the presented model is at mathematical level. From the mathematical viewpoint, we provide a general modeling framework for the process of radiopharmaceutical distribution in the tumor microenvironment to enable an analysis of the effect of various tumor-related parameters on the distribution of different radiopharmaceuticals.

Synthetic 18F-FDG PET Image Generation Using a Combination of Biomathematical Modeling and Machine Learning.

No previous works have attempted to combine generative adversarial network (GAN) architectures and the biomathematical modeling of positron emission tomography (PET) radiotracer uptake in tumors to generate extra training samples. Here, we developed a novel computational model to produce synthetic 18F-fluorodeoxyglucose (18F-FDG) PET images of solid tumors in different stages of progression and angiogenesis. First, a comprehensive biomathematical model is employed for creating tumor-induced angiogenesis, intravascular and extravascular fluid flow, as well as modeling of the transport phenomena and reaction processes of 18F-FDG in a tumor microenvironment.

Analysis of Magneto-Hyperthermia Duration in Nano-sized Drug Delivery System to Solid Tumors Using Intravascular-Triggered Thermosensitive-Liposome.

Computational models have been developed as a potential platform to identify bio-interactions that cannot be properly understood by experimental models. In the present study, a mathematical model has been employed to investigate the therapeutic response of drug-loaded thermosensitive liposome (TSL) following intravascular release paradigm. Thermal field created by an alternating magnetic field is utilized to release the drug within microvessels.

Towards principled design of cancer nanomedicine to accelerate clinical translation.

Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application.

Computational Modeling of Combination of Magnetic Hyperthermia and Temperature-Sensitive Liposome for Controlled Drug Release in Solid Tumor.

Combination therapy, a treatment modality that combines two or more therapeutic methods, provides a novel pathway for cancer treatment, as it targets the region of interest (ROI) in a characteristically synergistic or additive manner. To date, liposomes are the only nano-drug delivery platforms that have been used in clinical trials. Here, we speculated that it could be promising to improve treatment efficacy and reduce side effects by intravenous administration of thermo-sensitive liposomes loaded with doxorubicin (TSL-Dox) during magnetic hyperthermia (MHT).

Computational modeling of PET tracer distribution in solid tumors integrating microvasculature.

Background: We present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection-Diffusion-Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues.

Engineered strategies to enhance tumor penetration of drug-loaded nanoparticles.

Nanocarriers have been widely employed in preclinical studies and clinical trials for the delivery of anticancer drugs. The most important causes of failure in clinical translation of nanocarriers is their inefficient accumulation and penetration which arises from special characteristics of tumor microenvironment such as insufficient blood supply, dense extracellular matrix, and elevated interstitial fluid pressure. Various strategies such as engineering extracellular matrix, optimizing the physicochemical properties of nanocarriers have been proposed to increase the depth of tumor penetration; however, these strategies have not been very successful so far.

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach.

The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence.

Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors.

For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study.

Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors.

One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented based on extravascular drug release paradigm.

Enhanced Drug Delivery to Solid Tumors via Drug-Loaded Nanocarriers: An Image-Based Computational Framework.

Objective: Nano-sized drug delivery systems (NSDDSs) offer a promising therapeutic technology with sufficient biocompatibility, stability, and drug-loading rates towards efficient drug delivery to solid tumors. We aim to apply a multi-scale computational model for evaluating drug delivery to predict treatment efficacy.

Methodology: Three strategies for drug delivery, namely conventional chemotherapy (one-stage), as well as chemotherapy through two- and three-stage NSDDSs, were simulated and compared.

Enhancing Clinical Translation of Cancer Using Nanoinformatics.

Application of drugs in high doses has been required due to the limitations of no specificity, short circulation half-lives, as well as low bioavailability and solubility. Higher toxicity is the result of high dosage administration of drug molecules that increase the side effects of the drugs. Recently, nanomedicine, that is the utilization of nanotechnology in healthcare with clinical applications, has made many advancements in the areas of cancer diagnosis and therapy.

Controlled anti-cancer drug release through advanced nano-drug delivery systems: Static and dynamic targeting strategies.

Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery.