Digital Twins of Biological Systems: A Narrative Review.

The concept of Digital Twins (DTs), software models that mimic the behavior and interactions of physical or conceptual objects within their environments, has gained traction in recent years, particularly in medicine and healthcare research. DTs technology emerges as a pivotal tool in disease modeling, integrating diverse data sources to computationally model dynamic biological systems. This narrative review explores potential DT applications in medicine, from defining DTs and their history to constructing DTs, modeling biologically relevant systems, as well as discussing the benefits, risks, and challenges in their application. The influence of DTs extends beyond healthcare and can revolutionize healthcare management, drug development, clinical trials, and various biomedical research fields.

Targeting Breast Cancer Using Hyaluronic Acid-Conjugated Liposomes Triggered with Ultrasound.

The successful targeting of tumors can be achieved by conjugating targeting moieties to nanoparticles. These modifications allow nannocarriers to achieve greater targeting specificity through binding to specific receptors overexpressed on the surface of the tumor cells. In this study, pegylated liposomes encapsulating the model drug/dye calcein and conjugated to hyaluronic acid (HA) molecules were successfully synthesized, and their ability to target HA receptors overexpressed on a breast cancer cell line was investigated in vitro. Low-frequency ultrasound (LFUS), applied at three different power densities (6.2, 9, and 10 mW/cm²) were used to trigger the release of the entrapped calcein. Both the control and HAconjugated liposomes showed similar release profiles. HA conjugation to the liposomes resulted in a significant increase in calcein uptake by the breast cancer cell line MDA-MB-231 known for its CD44 (HA receptor) overexpression, while such an effect was not recorded with NIH-3T3, an embryonic mouse fibroblast, with low levels of CD44 expression. The application of low LFUS showed a significant enhancement of calcein uptake by MDA-MB-231 cells from our liposome compared to calcein uptake without cell exposure to ultrasound. These findings suggest that combining HA-conjugated liposomes with ultrasound is a promising drug delivery platform in breast cancer treatment.

Ultrasound-Triggered Immunotherapy for Cancer Treatment: An Update.

Over the past few decades, immunotherapy has emerged as a promising therapeutic approach to treat some types of cancer. Moreover, antibody-based cancer therapies can trigger apoptosis and cell growth inhibition to induce immune cell destruction of target cells through antibody-dependent cellular cytotoxicity (ADCC). Nevertheless, immunotherapeutic efficiency is often restricted due to deficient delivery or low accumulation of therapeutic molecules at the tumor site. The development of pegylated liposomes with monoclonal antibodies conjugated to their surfaces (immunoliposomes) and triggered with ultrasound can effectively improve drug accessibility by enhancing cell membrane permeability and drug release. This review summarizes existing traditional cancer treatments and their limitations, emphasizing the recent advancements in ultrasound-triggered immunotherapy.

Ultrasound-Mediated Drug Delivery in Cancer Therapy: A Review.

The use of ultrasound as a medical diagnostic tool began in the 1940s. Ever since, the medical applications of ultrasound have included imaging, tumor ablation, and lithotripsy; however, an ever-increasing body of literature demonstrates that ultrasound has potential in other medical applications, including targeted drug delivery. Site-specific drug delivery involves delivering drugs to diseased areas with a high degree of precision, which is particularly advantageous in cancer treatment as it would minimize the adverse side effects experienced by patients. This review addresses the ability of ultrasound to induce localized and controlled drug release from nanocarriers, namely micelles and liposomes, utilizing thermal and/or mechanical effects. The interactions of ultrasound with micelles and liposomes, the effects of the lipid composition, and ultrasound parameters on the release of encapsulated drugs are discussed. In addition, a survey of the literature detailing some in vitro and in vivo ultrasound triggered drug delivery systems is presented.

Effect of Pegylation and Targeting Moieties on the Ultrasound-Mediated Drug Release from Liposomes.

The use of targeted liposomes encapsulating chemotherapy drugs enhances the specific targeting of cancer cells, thus reducing the side effects of these drugs and providing patient-friendly chemotherapy treatment. Targeted pegylated (stealth) liposomes have the ability to safely deliver their loaded drugs to the cancer cells by targeting specific receptors overly expressed on the surface of these cells. Applying ultrasound as an external stimulus will safely trigger drug release from these liposomes in a controlled manner. In this study, we investigated the release kinetics of the model drug "calcein" from targeted liposomes sonicated with low-frequency ultrasound (20 kHz). Our results showed that pegylated liposomes were more sonosensitive compared to nonpegylated liposomes. A comparison of the effect of three targeting moieties conjugated to the surface of pegylated liposomes, namely human serum albumin (HSA), transferrin (Tf) and arginylglycylaspartic acid (RGD), on calcein release kinetics was conducted. The fluorescent results showed that HSA-PEG and Tf-PEG liposomes were more sonosensitive (showing higher calcein release following the exposure to pulsed LFUS) compared to the control pegylated liposomes, thus adding more acoustic benefits to their targeting efficacy.