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Updated: May 3, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma
Nirupama Sabnis1, Suraj Pratap2, Irina Akopova1
1Molecular Biology/Immunology, University of North Texas Health Science Center Fort Worth, TX, USA.
Abstract:
Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30-50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel approach to current NB therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC50 values for the rHDL encapsulated FR vs. free FR. More importantly, the IC50 value for retinal pigment epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100-fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and NB in particular.
Insights
Fenretinide (FR) nanoparticles encapsulated in reconstituted high-density lipoprotein (rHDL) show promise for treating high-risk neuroblastoma (HRNB). This novel drug delivery system enhances therapeutic efficacy and reduces toxicity in pediatric cancer models.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Pediatric high-risk neuroblastoma (HRNB) has poor long-term survival rates (30-50%) despite advances in research.
- Therapeutic resistance and off-target toxicity limit current chemotherapy for HRNB.
- Novel strategies are crucial to improve survival and prevent relapse in HRNB patients.
Purpose of the Study:
- To evaluate reconstituted high-density lipoprotein (rHDL) nanoparticles containing fenretinide (FR) as a novel therapeutic approach for neuroblastoma (NB).
- To assess the characterization, stability, and in vitro efficacy of rHDL-FR nanoparticles.
- To determine the potential of this drug delivery platform to overcome resistance and reduce toxicity in NB treatment.
Main Methods:
- Formulation and characterization of rHDL-FR nanoparticles, including size and encapsulation efficiency.
- In vitro cytotoxicity studies comparing free FR with rHDL-FR on NB cell lines (SK-N-SH, SMS-KCNR).
- Assessment of off-target toxicity by evaluating IC50 values in retinal pigment epithelial cells (ARPE-19).
Main Results:
- rHDL-FR nanoparticles exhibited small size (<40 nm) and high encapsulation efficiency.
- rHDL-FR demonstrated significantly lower IC50 values (2.8-fold and 2-fold) against NB cell lines compared to free FR.
- rHDL-FR showed over 40-fold higher IC50 in ARPE-19 cells, indicating reduced off-target toxicity.
Conclusions:
- Encapsulation of FR into rHDL nanoparticles resulted in approximately 100-fold improvement in selective therapeutic efficiency in vitro.
- The rHDL-FR nanoparticle platform shows significant potential for treating pediatric cancers, particularly neuroblastoma.
- This novel drug delivery system offers a promising strategy to enhance efficacy and minimize toxicity in NB therapy.
