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Atezolizumab-Conjugated Poly(lactic acid)/Poly(vinyl alcohol) Nanoparticles as Pharmaceutical Part Candidates for
Meliha Ekinci1, Clenilton Costa Dos Santos2, Luciana Magalhães Rebelo Alencar3
1Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, 35040 Izmir, Turkiye.
Abstract:
The necessity of new drugs for lung cancer therapy and imaging is increasing each day. The development of new drugs that are capable of reaching the tumor with specificity and selectivity is required. In this direction, the design of nanoparticles for tumor therapy represents an important alternative. The aim of this study was to develop, characterize, and evaluate target-specific atezolizumab-conjugated poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticles as pharmaceutical fragment candidates for new radiopharmaceuticals. For this purpose, PLA/PVA nanoparticle formulations were prepared by the double emulsification/solvent evaporation method with a high-speed homogenizer. A special focus was oriented to the selection of a suitable method for modification of the nanoparticle surface with a monoclonal antibody. For this purpose, atezolizumab was bound to the nanoparticles during the preparation by solvent evaporation or either by adsorption or covalent binding. PLA/PVA/atezolizumab nanoparticles are characterized by dynamic light scattering, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy. An in vitro assay was performed to evaluate the antibody binding efficiency, stability, and cytotoxicity [A549 (lung cancer cell) and L929 (healthy fibroblast cell)]. The results showed that a spherical nanoparticle with a size of 230.6 ± 1.768 nm and a ζ potential of -2.23 ± 0.55 mV was produced. Raman spectroscopy demonstrated that the monoclonal antibody was entrapped in the nanoparticle. The high antibody binding efficiency (80.58%) demonstrated the efficacy of the nanosystem. The cytotoxic assay demonstrated the safety of the nanoparticle in L929 and the effect on A549. In conclusion, PLA/PVA/atezolizumab nanoparticles can be used as drug delivery systems for lung cancer diagnosis and therapy.
Insights
New poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticles conjugated with atezolizumab show promise for targeted lung cancer therapy and imaging. These nanoparticles demonstrate effective drug delivery and safety for potential use in radiopharmaceuticals.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Increasing need for novel lung cancer therapeutics and imaging agents.
- Targeted drug delivery systems are crucial for enhancing treatment efficacy and minimizing side effects.
- Nanoparticles offer a promising platform for developing advanced pharmaceutical agents.
Purpose of the Study:
- To develop and characterize atezolizumab-conjugated poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticles.
- To evaluate these nanoparticles as potential pharmaceutical fragments for novel radiopharmaceuticals.
- To assess the target specificity, stability, and safety of the developed nanosystem.
Main Methods:
- Preparation of PLA/PVA nanoparticles using the double emulsification/solvent evaporation method.
- Conjugation of atezolizumab (monoclonal antibody) to nanoparticles via solvent evaporation, adsorption, or covalent binding.
- Characterization using dynamic light scattering, Raman spectroscopy, SEM, and AFM; in vitro evaluation of antibody binding efficiency, stability, and cytotoxicity.
Main Results:
- Spherical nanoparticles with a size of ~230 nm and ζ potential of -2.23 mV were successfully produced.
- Raman spectroscopy confirmed the entrapment of atezolizumab within the nanoparticles.
- High antibody binding efficiency (80.58%) and demonstrated safety on healthy cells (L929) with efficacy against lung cancer cells (A549).
Conclusions:
- PLA/PVA/atezolizumab nanoparticles are effectively developed and characterized.
- The nanosystem exhibits high antibody binding efficiency and promising in vitro safety and efficacy profiles.
- These nanoparticles represent a viable drug delivery system for advanced lung cancer diagnosis and therapy.
