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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

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Nanoparticle-based strategy for personalized B-cell lymphoma therapy.

Nicola M Martucci¹, Nunzia Migliaccio¹, Immacolata Ruggiero¹

¹Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.

International Journal of Nanomedicine

|November 30, 2016

Summary

Researchers developed a novel personalized therapy for B-cell lymphoma using silica nanoparticles. These nanoparticles target lymphoma cells specifically, delivering small interfering RNA (siRNA) to reduce the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2).

Keywords:

Bcl2 active targeting diatomite personalized therapy small interfering RNA

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A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells

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Published on: October 16, 2018

Area of Science:

Nanomedicine
Oncology
Molecular Biology

Background:

B-cell lymphoma treatment often results in incomplete responses, necessitating novel therapeutic strategies.
Targeting specific molecular pathways, like the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2), is crucial for effective lymphoma therapy.

Purpose of the Study:

To develop a personalized, site-specific drug delivery system for B-cell lymphoma.
To utilize natural silica nanoparticles (diatomite) modified for targeted delivery of small interfering RNA (siRNA) against Bcl2.

Main Methods:

Modification of diatomite nanoparticles with an idiotype-specific peptide (Id-peptide) for homing to lymphoma cells.
Evaluation of nanoparticle uptake using flow cytometry and confocal microscopy, comparing Id-peptide targeted cells with control cells.
Assessment of gene silencing efficacy via quantitative real-time polymerase chain reaction and Western blot analyses targeting Bcl2.

Main Results:

Id-peptide mediated nanoparticle uptake increased approximately threefold in target lymphoma cells compared to nonspecific myeloma cells.
Specific internalization efficiency was enhanced fourfold upon addition of siRNA to the modified nanoparticles.
Modified diatomite nanoparticles demonstrated no cytotoxicity and effectively downregulated Bcl2 gene expression.

Conclusions:

The developed Id-peptide targeted, siRNA-loaded diatomite nanoparticles show significant potential for personalized B-cell lymphoma treatment.
This approach offers a promising strategy for gene silencing in lymphomas, addressing challenges in treatment response.