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. A hybrid sprouting angiogenesis approach generates a semi-realistic microvascular network to evaluate therapeutic drug distribution and microvascular heterogeneity. A pharmacodynamics model evaluates treatment success based on tumor survival cell percentage. The study found that whereas bolus injection boosted extracellular drug concentration levels by 90%, continuous infusion improved therapeutic response due to improved bioavailability. Cancer cell death increases by 6% with several injections compared to single injections due to prolonged chemotherapeutic medication exposure. However, responsive nanocarriers supply more than 2.1 times more drug than traditional chemotherapy in extracellular space, suppressing tumor development longer. Also, controlled drug release decreases systemic side effects substantial through diminishing the concentration of free drug in the circulation. The primary finding of this work highlights the significance of high bioavailability in treatment response. The results indicate that responsive nanocarriers contribute to increased bioavailability, leading to improved therapeutic benefits. By including drug delivery features in a semi-realistic model, this numerical study sought to improve drug-bio interaction comprehension. The model provides a good framework for understanding preclinical and clinical targeted oncology study outcomes.

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. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems.

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. We argue that partial differential equations (PDEs), beyond conventional methods, including ODE-based kinetic compartment modeling, can be used to evaluate radiopharmaceutical distribution in both time and space. In addition, we consider the spatially-variable dynamic structure of tumor microvascular networks to simulate blood flow distribution. To examine the robustness of the model, the effects of microvessel density (MVD) and tumor size, as two important factors in tumor prognosis, on the radiopharmaceutical distribution within the tumor are investigated over time (in the present work, we focus on the radiopharmaceutical [18F]FDG, yet the framework is broadly applicable to radiopharmaceuticals). Results demonstrate that the maximum total uptake of [18F]FDG at all time frames occurs in the tumor area due to the high capillary permeability and lack of a functional lymphatic system. As the MVD of networks increases, the mean total uptake in the tumor is also enhanced, where the rate of diffusion from vessel to tissue has the highest contribution and the rate of convection transport has the lowest contribution. The results of this study can be used to better investigate various phenomena and bridge a gap among cancer biology, mathematical oncology, medical physics, and radiology.

3D Printed Hydrogels for Ocular Wound Healing.

Corneal disease is one of the most significant causes of blindness around the world. Presently, corneal transplantation is the only way to treat cornea blindness. It should be noted that the amount of cornea that people donate is so much less than that required (1:70). Therefore, scientists have tried to resolve this problem with tissue engineering and regenerative medicine. Fabricating cornea with traditional methods is difficult due to their unique properties, such as transparency and geometry. Bioprinting is a technology based on additive manufacturing that can use different biomaterials as bioink for tissue engineering, and the emergence of 3D bioprinting presents a clear possibility to overcome this problem. This new technology requires special materials for printing scaffolds with acceptable biocompatibility. Hydrogels have received significant attention in the past 50 years, and they have been distinguished from other materials because of their unique and outstanding properties. Therefore, hydrogels could be a good bioink for the bioprinting of different scaffolds for corneal tissue engineering. In this review, we discuss the use of different types of hydrogel for bioink for corneal tissue engineering and various methods that have been used for bioprinting. Furthermore, the properties of hydrogels and different types of hydrogels are described.

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. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field.

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. Novel strategies such as transformable nanocarriers, transcellular transport of peptide-modified nanocarriers, and bio-inspired carriers have recently been emerged as an advanced generation of drug carriers. In this study, the latest developments of nanocarrier-based drug delivery to solid tumor are presented with their possible limitations. Then, the prospects of advanced drug delivery systems are discussed in detail.