Table 2 Summary of the nanocarriers employed in the treatment of RB

Organic nanoparticles

Mudigunda et al. reported the effectiveness of hybrid PLGA/PCL NPs loading Palbociclib as well as a photothermal dye on Y79 RB cells with higher drug bioavailability in these cells compared to drug control

[78]

Sims et al. demonstrated the effectiveness of intra-arterial surface-tailored PLGA-NPs carrying melphalan for RB management paving the way for in-vivo application

[79]

Silva et al. demonstrated that PLGA-ursolic acid/oleanolic acid nanoparticles showed strong cytotoxic activity against RB cell line

[80]

Narayana et al. documented the efficacy of clinical-grade carboplatin and etoposide-loaded lactoferrin nanoparticles on RB y79 in terms of increasing drug retention, uptake and cytotoxicity compared to their standard drugs

[81]

Ahmed et al. demonstrated the potential of carboplatin loaded lactoferrin nanoparticles with high anti-proliferative activity into the RB cells compared to the drug alone

[82]

Lipid nanoparticles (LNPs)

Xu et al. reported the efficacy of switchable LNPs for the co-delivery of miR-181 and melphalan with good efficacy against RB

[83]

N’Diaye et al. demonstrated the efficaciousness of LNPs incorporating beta-lapachone and temoporfin against RB Y79 cells, in which they could be supplied in a single intravitreal injection for treatment of RB

[84]

Solid lipid nanoparticles (SLNs)

Ahmad et al. showed the effectiveness of injectable etoposide SLNs for achieving safe and targeted drug against RB

[87]

Nanostructured lipid carriers (NLCs)

Almedia et al. reported the effectiveness of an eye drop containing ibuprofen dispersion encompassing a combination of NLCs and a thermo-responsive polymer with considerable cytotoxicity, improved bioavailability, and therapeutic effectiveness, besides sustained-release drug profiles

[89]

Doxorubicin (DOX)-loaded poly-B-hydroxybutyrate microspheres

Hu et al. showed the functionality of these microspheres to extend DOX release to the posterior eyes' segment

[96]

Carboplatin hyper-branched PAMAM dendritic nanoparticles

Kang et al. proved the potential of carboplatin loaded on dendrimer type PAMAM to increase carboplatin's bioavailability which inhibited toxicity and tumor mass in RB compared to free carboplatin

[97]

Makky et al. proved an enhanced targeting and reduced toxicity outcomes when loading concanavalin in dendritic nanoparticles for treatment of intraocular tumors and RB

[98]

Polymeric nanoparticles

Arshad et al. proved that the successfulness of chitosan nanoparticles for delivering DOX to the Y79 RB cell line with increased folate receptor concentration

[100]

Delrish et al. demonstrated the augmented efficacy of thiolated chitosan nanoparticles comprising topotecan relative to free topotecan in Y79 RB cells

[101]

Delrish et al. demonstrated increased ocular bioavailability of thiolated chitosan carboxymethyl dextran nanoparticles in retinoblastoma induced rat eyes

[102]

Godse et al. revealed that galactose conjugated chitosan nanoparticles loaded with etoposide exhibited greater cytotoxicity and resulted in higher apoptosis in RB Y-79 cells relative to pure etoposide

[103]

Mohseni et al. demonstrated that lauric acid-grafted chitosan-alginate nanoparticles incorporating melphalan enhanced its penetrability to the vitreous cavity with augmented efficacy, delineating their potential for RB treatment

[104]

Boddu et al. reported that a micellar system comprising DOX exhibited a two-week continuous release of the drug and a fourfold increase in cell absorption over the free drug

[105]

Das and Sahoo emphasized that folate-tagged PLGA nanoparticles containing curcumin and nutlin-3a were able to reverse multidrug resistance (MDR) pathways and increase cancer cell apoptosis, expanding therapeutic efficacy for RB treatment

[106]

Rebibo et al. revealed the superior efficacy of tacrolimus-loaded PLGA nanocapsules for RB treatment in augmenting drug's retention and enhancing penetration to posterior eye compartments

[107]

Silver NPs (AgNPs)

Remya et al. reported the cytotoxic efficiency of AgNPs derived from natural sources of brown seaweed Turbinaria ornata against RB cells

[110]

Rajanahalli et al. revealed that AgNPs resulted in cell cycle arrest in G1, and S phases mediated by repression of RB protein phosphorylation using stem mouse embryonic stem cells

[111]

Gold NPs (AuNPs)

Wang et al. proved the cytotoxicity of gold nanocages linked with iron oxide NPs in retinal pigment epithelium cells and RB Y79 cells, indicating that the system was physiologically safe and potential for further use

[113]

Iron oxide NPs

Demirci et al. revealed that magnetic hyperthermia in the Y79 RB cell line utilizing dextran-coated iron nanoparticles resulted in the apoptosis of 46% to 73% of Y79 RB cells

[114]

Mesoporous silica NPs (MSNPs)

Gallud et al. reported the efficacy of functionalized mesoporous nanoparticles loaded with camptothecin in treating RB using Y79 cells

[117]

Qu et al. demonstrated that carboplatin loaded in MSNPs increased cancer cell death in RB cells compared to free carboplatin

[118]

Gary-Bobo et al. showed the effectiveness of camptothecin, mannose, or galactose in MSNPs against Y-79 RB cells

[119]

Warther et al. reported the efficacy of mannose-functionalized MSNPs for targeting and imaging RB cells

[120]

Cerium oxide NPs (CeONPs)

Stephen and Chen displayed the efficacy of CeONPs in inhibiting the apoptotic signaling pathway of RB Y78 cell lines, increasing the expression of genes associated with neuroprotection

[122]

Gao et al. demonstrated the efficacy of glycolic chitosan-coated cerium nanoparticles loaded with DOX in the significant inhibition of tumor growth as well as the biocompatibility of the proposed NPs with normal retinal cells in-vivo

[124]

Kartha et al. revealed the superiority of cerium-doped titanium dioxide nanoparticles in augmenting anticancer cytotoxicity compared to titanium dioxide nanoparticles

[125]

Surface-modified Melphalan nanoparticles

Farhat et al. revealed that surface-modified melphalan nanoparticles exhibited superior association and effectiveness against RB cells for RB intravitreal chemotherapy

[128]

Galactose-functionalized nanocarriers

Godse et al. reported that etoposide loaded PLGA nanoparticles coated with chitosan and galactose improved the drug’s cellular internalization, promoting superior anti-cancer activity

[100]

Hyaluronic acid (HA)-functionalized nanocarriers

Martens et al. reported that the formulation of electrostatically coated nanoparticles incorporating nonverbal polymeric gene DNA complexed with HA provided increased intravitreal mobility in RB cells

[126]

Folic acid (FA)-functionalized nanocarriers

Mitra et al. reported that DOX conjugated with folic acid proved their efficacy for targeting RB cells

[128]