SEARCHNARRATIVE_REVIEWophthalmology, pediatric ophthalmology

narrative_review·ophthalmology, pediatric ophthalmology, nanomedicine, oncology·PMC10496918

Nanoparticle-based delivery systems as emerging therapy in retinoblastoma: recent advances, challenges and prospects

Nanoscale Advances · 11 authors, 7 centres

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TL;DR

This review summarizes the current and emerging nanoparticle-based therapies for retinoblastoma, highlighting that nanocarriers such as gold, silver, iron oxide, mesoporous silica, cerium oxide, lipid, and polymeric nanoparticles can improve targeted drug delivery, enhance bioavailability, and reduce systemic toxicity compared to conventional treatments. The paper emphasizes that ligand-conjugated and smart nanoparticles show promise in actively targeting retinoblastoma cells, but clinical translation remains limited due to challenges like ocular barriers, scalability, and toxicity. The clinical significance lies in the potential of these systems to improve treatment efficacy, reduce side effects, and increase survival rates for children with retinoblastoma.

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**Background:** Retinoblastoma is the most common intraocular malignancy in children, with an average incidence of 1 in 17,000 births. It results from mutations in the RB1 tumour suppressor gene, leading to unregulated cell proliferation. Current treatments include surgery (enucleation), radiotherapy, cryotherapy, laser therapy, and chemotherapy (systemic or local). However, these therapies are associated with significant adverse effects, such as organ damage, secondary cancers, and vision loss, particularly due to non-specific distribution of chemotherapeutic agents. Nanoparticle-based delivery systems offer potential advantages, including targeted delivery, enhanced permeability and retention effects, increased bioavailability, and improved toxicity profiles. This review aims to discuss recent advances, challenges, and prospects of using various nanoparticle classes for diagnosing and treating retinoblastoma.

**Methods:** This is a narrative review that synthesizes findings from published studies on nanoparticle-based delivery systems for retinoblastoma. The authors searched for and analyzed literature covering inorganic nanoparticles (gold, silver, iron oxide, mesoporous silica, cerium oxide), lipid nanoparticles (liposomes, solid lipid nanoparticles, nanostructured lipid carriers), and polymeric nanoparticles. They also reviewed studies on active targeting using ligand-conjugated nanoparticles (e.g., folic acid, galactose, mannose, lactoferrin, EpCAM antibodies) and smart nanoparticles responsive to stimuli such as pH, reactive oxygen species, and hyperthermia. The review includes in vitro and in vivo studies, as well as preclinical models, but does not describe a systematic search strategy or meta-analysis.

**Key Results:** The review reports several key findings from individual studies: - Gold nanoparticles (GNPs) combined with ultrasonic hyperthermia in a rabbit model led to depletion of relative tumour size and increased cell death. - Silver nanoparticles (AgNPs) synthesized from *Turbinaria ornata* showed an IC50 of 10.5 μg/mL against Y79 retinoblastoma cells. - Dextran-coated iron oxide nanoparticles (IONPs) at concentrations ≥0.5 mg/mL selectively destroyed >70% of Y79 cells via magnetic hyperthermia. - Folic acid-conjugated mesoporous silica nanoparticles (FA-MSNs) loaded with topotecan induced up to 58% apoptosis in Y79 cells and showed greater tumour-inhibitory effects in vivo compared to non-targeted formulations. - Cerium oxide nanoparticles (CNPs) caused >50% decrease in tumour size in a mouse model (P53TKO mice) after a single intravitreal injection. - Lipid nanoparticles (LNPs) co-delivering melphalan and miR-181 achieved 93% encapsulation efficiency for miR-181 and enhanced apoptotic gene expression. - Etoposide-loaded solid lipid nanoparticles (SLNs) provided prolonged drug release over 7 days with a single intravitreal injection and showed no toxicity in histological studies. - Polymeric nanoparticles (PNPs) loaded with palbociclib and near-infrared dye (IR820) enhanced cytotoxic killing (86.5 ± 2.3%) in Y79 cells upon NIR light exposure. - Phytochemical-loaded nanoparticles, such as curcumin-difluorinated loaded polymeric micelles, showed high encapsulation efficiency (>85%) and significant killing of Y79 and WERI-RB cells without harming ARPE-19 cells. - Active targeting studies: Galactose–chitosan conjugated PLGA nanoparticles achieved 70% cellular uptake in retinoblastoma cells; lactoferrin-conjugated nanoparticles enhanced carboplatin uptake and cytotoxicity; EpCAM antibody-conjugated gold nanoparticles downregulated EpCAM gene expression in Y79 cells.

**Clinical Implications:** The review underscores that nanoparticle-based delivery systems hold great potential to revolutionize retinoblastoma therapy by improving drug targeting, reducing systemic toxicity, and enabling combination therapies (e.g., chemo-photodynamic therapy). However, clinical translation is hindered by ocular barriers (blood–retinal and blood–aqueous barriers), batch-to-batch reproducibility issues, and the need for relevant animal models. The authors advocate for further research into smart nanoparticles responsive to tumour microenvironment stimuli, multifunctional theranostic nanoparticles, and combination therapies to overcome multidrug resistance and improve patient outcomes. The development of non-invasive, sustained-release systems could enhance compliance and reduce the need for enucleation, particularly in developing countries where late diagnosis is common.

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narrative_review

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ophthalmology

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ORIGINAL PAPER

PMC10496918

Nanoparticle-based delivery systems as emerging therapy in retinoblastoma: recent advances, challenges and prospects

Nanoscale Advances

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ABSTRACT

Retinoblastoma is the most common intraocular malignancy in children. The treatment of this rare disease is still challenging in developing countries due to delayed diagnosis. The current therapies comprise mainly surgery, radiotherapy and chemotherapy. The adverse effects of radiation and chemotherapeutic drugs have been reported to contribute to the high mortality rate and affect patients' quality of life. The systemic side effects resulting from the distribution of chemotherapeutic drugs to non-cancerous cells are enormous and have been recognized as one of the reasons why most potent anticancer compounds fail in clinical trials. Nanoparticulate delivery systems have the potential to revolutionize cancer treatment by offering targeted delivery, enhanced penetration and retention effects, increased bioavailability, and an improved toxicity profile. Notwithstanding the plethora of evidence on the beneficial effects of nanoparticles in retinoblastoma, the clinical translation of this carrier is yet to be given the needed attention. This paper reviews the current and emerging treatment options for retinoblastoma, with emphasis on recent investigations on the use of various classes of nanoparticles in diagnosing and treating retinoblastoma. It also presents the use of ligand-conjugated and smart nanoparticles in the active targeting of anticancer and imaging agents to the tumour cells. In addition, this review discusses the prospects and challenges in translating this nanocarrier into clinical use for retinoblastoma therapy. This review may provide new insight for formulation scientists to explore in order to facilitate the development of more effective and safer medicines for children suffering from retinoblastoma.

CITATION EXPORT

Adaeze Linda Onugwu, Onyinyechi Lydia Ugorji, Chinasa A. Ufondu et al.. Nanoparticle-based delivery systems as emerging therapy in retinoblastoma: recent advances, challenges and prospects. Nanoscale Advances. (2023). https://doi.org/10.1039/d3na00462g

AUTHORS

11 · 7 CENTRES

Adaeze Linda Onugwu, Onyinyechi Lydia Ugorji, Chinasa A. Ufondu, Stella Amarachi Ihim, Adaeze Chidiebere Echezona, Chinekwu Sherridan Nwagwu, Sabastine Obinna Onugwu, Samuel WisdomofGod Uzondu, Chinazom Precious Agbo, John Dike Ogbonna, Anthony Amaechi Attama

a Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria Nsukka Enugu State Nigeria [email protected] [email protected]
b Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria Nsukka Enugu State Nigeria
c Molecular Pharmacology and Therapeutics, Department of Pharmacology, University of Minnesota Twin Cities USA
d Department of Science Laboratory Technology (Physiology and Pharmacology Unit), University of Nigeria Nsukka Enugu State Nigeria
e Department of Pharmacognosy, Enugu State University of Science and Technology Enugu State Nigeria
f NanoMalaria Research Unit, Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, University of Nigeria Nsukka Enugu State Nigeria
g Institute for Drug-Herbal Medicine-Excipient Research and Development, University of Nigeria Nsukka Enugu State Nigeria