Cathepsin B is a lysosomal cysteine protease, contributing to vital cellular homeostatic processes including protein turnover, macroautophagy of damaged organelles, antigen presentation, and in the extracellular space, it takes part in tissue remodeling, prohormone processing, and activation. However, aberrant overexpression of cathepsin B and its enzymatic activity is associated with different pathological conditions, including cancer. Cathepsin B overexpression in tumor tissues makes this enzyme an important target for smart delivery systems, responsive to the activity of this enzyme. The generation of technologies which therapeutic effect is activated as a result of cathepsin B cleavage provides an opportunity for tumor-targeted therapy and controlled drug release. In this review, we summarized different technologies designed to improve current cancer treatments responsive to the activity of this enzyme that were shown to play a key role in disease progression and response to the treatment.

Cancer treatment and pharmaceutical development require targeted treatment and less toxic therapeutic intervention to achieve real progress against this disease. In this scenario, nanomedicine emerged as a reliable tool to improve drug pharmacokinetics and to translate to the clinical biologics based on large molecules. However, the ability of our body to recognize foreign objects together with carrier transport heterogeneity derived from the combination of particle physical and chemical properties, payload and surface modification, make the designing of effective carriers very difficult. In this scenario, physiologically based pharmacokinetic modeling can help to design the particles and eventually predict their ability to reach the target and treat the tumor. This effort is performed by scientists with specific expertise and skills and familiarity with artificial intelligence tools such as advanced software that are not usually in the “cords” of traditional medical or material researchers. The goal of this review was to highlight the advantages that computational modeling could provide to nanomedicine and bring together scientists with different background by portraying in the most simple way the work of computational developers through the description of the tools that they use to predict nanoparticle transport and tumor targeting in our body.

Cancer remains a significant challenge for public healthcare systems worldwide. Within the realm of cancer treatment, considerable attention is focused on understanding the tumor microenvironment (TME)—the complex network of non-cancerous elements surrounding the tumor. Among the cells in TME, tumor-associated macrophages (TAMs) play a central role, traditionally categorized as pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages. Within the TME, M2-like TAMs can create a protective environment conducive to tumor growth and progression. These TAMs secrete a range of factors and molecules that facilitate tumor angiogenesis, increased vascular permeability, chemoresistance, and metastasis. In response to this challenge, efforts are underway to develop adjuvant therapy options aimed at reprogramming TAMs from the M2 to the anti-tumor M1 phenotype. Such reprogramming holds promise for suppressing tumor growth, alleviating chemoresistance, and impeding metastasis. Nanotechnology has enabled the development of nanoformulations that may soon offer healthcare providers the tools to achieve targeted drug delivery, controlled drug release within the TME for TAM reprogramming and reduce drug-related adverse events. In this review, we have synthesized the latest data on TAM polarization in response to TME factors, highlighted the pathological effects of TAMs, and provided insights into existing nanotechnologies aimed at TAM reprogramming and depletion.

Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced physical activity. Two types of adipose tissue widely known are white and brown. While white adipose tissue functions predominantly as a key energy storage, brown adipose tissue has a greater mass of mitochondria and expresses the uncoupling protein 1 (UCP1) gene, which allows thermogenesis and rapid catabolism. Even though white and brown adipocytes are of different origin, activation of the brown adipocyte differentiation program in white adipose tissue cells forces them to transdifferentiate into “beige” adipocytes, characterized by thermogenesis and intensive lipolysis. Nowadays, researchers in the field of small molecule medicinal chemistry and gene therapy are making efforts to develop new drugs that effectively overcome insulin resistance and counteract obesity. Here, we discuss various aspects of white-to-beige conversion, adipose tissue catabolic re-activation, and non-shivering thermogenesis.

Proteolytic activity is pivotal in maintaining cell homeostasis and function. In pathological conditions such as cancer, it covers a key role in tumor cell viability, spreading to distant organs, and response to the treatment. Endosomes represent one of the major sites of cellular proteolytic activity and very often represent the final destination of internalized nanoformulations. However, little information about nanoparticle impact on the biology of these organelles is available even though they represent the major location of drug release. In this work, we generated albumin nanoparticles with a different resistance to proteolysis by finely tuning the amount of cross-linker used to stabilize the carriers. After careful characterization of the particles and measurement of their degradation in proteolytic conditions, we determined a relationship between their sensitivity to proteases and their drug delivery properties. These phenomena were characterized by an overall increase in the expression of cathepsin proteases regardless of the different sensitivity of the particles to proteolytic degradation.

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation.