Nanoparticle-based strategy for personalized B-cell lymphoma therapy

Abstract

B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas

Internalization kinetics and cytoplasmic localization of functionalized diatomite nanoparticles in cancer cells by Raman imaging

“…In our previous works, siRNA‐modified DNPs, once internalized by cancer cells, were demonstrated as efficient nanocarriers able to successfully release biologically active siRNA into the cytoplasm . Toxicity tests performed as a function of NP doses and times highlighted that the presence of DNPs did not affect cell viability .…”

“…Their unique nanoscale properties, thermal/chemical stability and low systemic toxicity render the DNPs an appealing system for drug delivery . DNPs were previously designed and optimized in terms of size, shape, surface charge and chemistry or modified with specific targeting ligands to explore their use in several biomedical applications, specifically for therapeutic applications of siRNA .…”

“…In our previous works, siRNA‐modified DNPs, once internalized by cancer cells, were demonstrated as efficient nanocarriers able to successfully release biologically active siRNA into the cytoplasm . Toxicity tests performed as a function of NP doses and times highlighted that the presence of DNPs did not affect cell viability . Cell uptake and distribution of functionalized DNPs have been routinely analyzed by confocal fluorescence microscopy, using a fluorochrome‐labeled siRNA and transmission electron microscopy (TEM) .…”

Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma

“…Diatomite NPs, silica-based NPs of irregular shape and mean size of approximately 200 nm, were also applied in the management of B-cell lymphoma (Martucci et al, 2016 ). These DNPs have been modified to actively target the hypervariable region of surface immunoglobulin B-cell receptor (BCR) toward fluorescence-based monitorization via FITC and confocal microscopy/flow cytometry.…”

Biocompatible Silver Nanoparticle-Modified Natural Diatomite with Anti-Infective Property

“…In recent years, diatomite with good biocompatibility has been exploited as carrier for drug/molecule delivery applications due to the unique properties such as highly porous structure, high surface area, and readily modifiable surface functionalities, demonstrating high potential in biotechnological applications [16][17][18][19]. For example, diatomite has been recently conjugated with peptide and loaded with small interfering RNA for B-cell lymphoma therapy [20]. In addition, metal-modified diatomites have been developed for the deposition of gold or palladium nanoparticles [21].…”