The use of nanoparticles has revolutionized drug delivery by enabling targeted and controlled therapeutic release. However, their interactions with intracellular organelles, particularly lysosomes, are not yet fully understood. This study delineates the differential effects of two widely used nanocarriers—mesoporous silica (MSNs) and albumin (ANPs) nanoparticles—on lysosomal biology, with a focus on the expression and activity of cathepsins (CtsB and CtsD), which are key proteases involved in protein degradation and maintaining cellular balance. These two types of nanoparticles, differing in their material and degradability, exhibit distinct behaviors inside the cell. We demonstrate that inorganic MSNs cause significant changes in lysosomal function by altering lysosomal content and cathepsin levels, without triggering lysosomal membrane permeabilization—a typical response to organic particle stress. In contrast, ANPs—which are susceptible to lysosomal cathepsin degradation—induce milder changes in cathepsin expression and maintain lysosomal integrity. Our results highlight that the composition of nanocarriers plays a pivotal role in modulating lysosomal protease activity and maintaining overall cellular homeostasis, highlighting the importance of these parameters in the rational design of drug delivery platforms.

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that uses photosensitizers (PSs) activated by light to produce cytotoxic reactive oxygen species (ROS). Although PDT shows clinical promise, its effectiveness is limited by factors such as insufficient tumor targeting, tumor hypoxia, PS instability, and weak immune responses. Biomimetic nanoparticles (BNPs), which combine natural biological materials like cell membranes with synthetic nanocarriers, have emerged as versatile platforms to overcome these challenges. BNPs improve PDT by enhancing tumor-specific delivery of PSs, relieving hypoxia through oxygen delivery or catalytic oxygen generation, and boosting antitumor immunity by promoting immunogenic cell death and working synergistically with immune checkpoint inhibitors. This review details recent progress in BNP-based strategies for targeted PS delivery, ROS production enhancement, hypoxia modulation, and immune system activation. Additionally, it explores multifunctional and theranostic nanoplatforms, their applications in various cancers, and advances toward clinical use. By integrating targeted delivery, tumor microenvironment modulation, and immunotherapy, BNP-facilitated PDT holds great potential for advancing precise cancer treatments.

This study investigates the enhancement of photodynamic therapy (PDT) efficacy through the encapsulation of platinum phthalocyanine (Pc) in albumin nanoparticles (ANP). Encapsulation of Pc in ANP) significantly enhances its biological effects in photodynamic therapy by increasing cellular uptake through receptor-mediated endocytosis and promoting lysosomal accumulation. This leads to marked lysosomal stress and regulated necrotic cell death pathway, while free Pc causes moderate oxidative stress with reversible apoptosis and autophagy. The enhanced phototoxicity of encapsulated Pc was evident across multiple cancer cell lines, especially aggressive phenotypes, whereas resistant lines showed lower sensitivity likely due to efficient ROS scavenging. Despite improved initial uptake, rapid lysosomal release and extracellular extrusion of Pc limit long-term intracellular retention. Morphological and gene expression analyses confirmed distinct cell death mechanisms between free and encapsulated Pc, underscoring the critical role of nanocarrier-mediated delivery in modulating oxidative stress and cellular response. These findings highlight the importance of nanoparticle design in optimizing PDT efficacy by effectively triggering necrotic cell death pathway.

In the tumor microenvironment, M2 tumor-associated macrophages play a crucial role in promoting tumor growth, vascularization, and metastasis through their anti-inflammatory and tissue-repairing functions. To reprogram M2 cells into a more benign M1 phenotype and enhance the patient’s intrinsic immune response against cancer, siRNA and small molecules are used, which can be encapsulated into nanoparticles to enhance their stability, circulation time, and bioavailability. Albumin nanoparticles are ideal candidates for the delivery of such cargo because of their low toxicity, biocompatibility, biodegradability, prolonged circulation in the bloodstream, and feasible particle modification. In this study, we optimized a one-step desolvation method using the standard cross-linker glutaraldehyde and D-mannose as a second cross-linker for the synthesis of mannosylated albumin nanoparticles. The obtained nanoparticles demonstrated favorable physical characteristics, high encapsulation efficiency, and the most effective targeting into activated M2 macrophages overexpressing the mannose receptor in comparison to M1 macrophages and cancer cells in vitro.

Subject of study. This study investigates free AgInS ₂ and AgInS ₂ /ZnS quantum dots and quantum dots encapsulated in albumin nanoparticles (ANPs). Aim of study. The aim of this study is to determine and compare the fluorescence properties and reactive oxygen species-generation abilities of free quantum dots and quantum dots encapsulated in ANPs for their use as photosensitizers (PSs) in photodynamic therapy (PDT). Method. The quantum dots were synthesized using a hydrothermal method, and the ANPs were obtained by the desolvation method. The quantum dots were encapsulated into the ANPs by co-incubation in aqueous solution. The efficiency of superoxide generation was evaluated using a selective chemical sensor. Main results. Growing a ZnS shell on AgInS ₂ quantum dots increased both their fluorescence quantum yield and efficiency of superoxide generation. The encapsulation efficiencies of AgInS ₂ and AgInS ₂ /ZnS quantum dots in ANPs were 60% and 20%, respectively, and they were accompanied by a hypsochromic shift in the fluorescence spectra of the quantum dots. Encapsulation of the quantum dots in ANPs led to a decrease in superoxide-generation efficiency compared with free quantum dots; however, this reduction may be compensated for by their greater stability in biological systems. Practical significance. The findings of this study on the photophysical properties of AgInS ₂ quantum dots demonstrate the high potential of nanoplatforms based on quantum dots and ANPs as PSs for PDT.