Table 2.
Organic and inorganic surface modification in curcumin–metal oxide nanoformulations and corresponding therapeutic performance.
| Therapeutic Agent | Synthesis Approach | Study Models | Outcomes |
|---|---|---|---|
| Folic acid (FA)/polyethylene glycol (PEG)/TiO2 [61] | Emulsion evaporation solidification | In vitro: MCF-7, MDA-MB-231, H9c2 In vivo: MDA-MB-231 tumor-bearing BALB/c mice |
In vitro: ↑ viability of H9c2 compared to only TiO2 treatment ↑ Cytotoxicity towards MCF-7 and MDA-MB-231 cells, cellular uptake by MCF-7 cells compared to untargeted NPs In vivo: ↑ drug concentration at the tumor site and better antitumor activity compared to untargeted NPs |
| PTX–cur-OAMNPPF127FA [62] | Fe3O4 by coprecipitation, surface functionalization by deposition from solution | MCF-7 | Lower hemolytic assay 4.1% ↑ Cellular uptake and growth inhibition of MCF-7 for active FA and passive magnetic field targeting Superparamagnetic behavior retained through lower saturation magnetization compared to MNP only |
| 5FU–CUR-C-MNP-HSA-FA [63] | MNPs by coprecipitation | MCF-7 | ↑ Colloidal stability, Superparamagnetic property maintained, but less saturation magnetization ↑ Cytotoxicity against MCF-7 ↑ Cellular uptake ↑Viability of MCF-7 cells, for FA targeted under magnetic field |
| Folic-acid-tagged aminated starch/ZnO-coated Fe3O4 [64] | Stirring together the nanocomposite and curcumin suspension overnight and genipin crosslinking | HepG2 and MCF7 | higher colloidal stability with zeta potential value of 42.9 mV, pH-dependent release profile → higher release rate at acidic pH, biocompatibility with human lymphocytes ↑ Cellular uptake and anticancer effect on MCF-7& HepG2 |
| Curcumin-incorporated TiO2-conjugated with MCP-1 antibody (CTNP-MCP-1) [65] | Suspending presynthesized CTNPs in MCP-1 antibody under stirring | Cholesterol-fed, atherosclerotic Sprague-Dawley rat | Normal ALP, GGT levels, RBC morphology, and aorta architecture for CTNP-MCP-1 treated rats → nontoxic ↑ Aortic concentration of CTNP-MCP-1 compared to CTNP → better targeting ↑ Half-life, distribution, and ↑ hydrolysis of curcumin in CTNPs → better stability MRI image contrast of CTNP-MCP-1 > CTNP due to targeting effect of MCP-1 antibody and ↑ paramagnetic property of TiO2 when combined with carbon compounds |
| FA-mPEG–PAMAM G3-CUR@SPIONs [12] | Coprecipitation for Fe3O4, dispersion of the constituents under sonication and mixing | KB and MCF-7 | ↑ KB cells (with higher FRs) lethality compared to MCF-7 (with lower FRS) |
| TiO2/polydopamine (pDA)/polycyclodextrin (pDC)-curcumin [66] | Hydrothermal synthesis of nanotube array on Ti substrates, followed by pDA and pCD coating and curcumin-loading | In vitro: MG63, In vivo: osteocarcinoma xenografted nude mice |
Membrane shrinkage, absence of filopodia and lamellipodia, ↓ Cell density of MG63 Biocompatibility towards MC3T3-E1 cells ↓ Tumor growth on osteocarcinoma xenografted nude mice |
| DOX and curcumin-loaded, HAPA/β-CD/SPION [67] | Fe3O4 by coprecipitation HAPA coating by coprecipitation, loaded β-CD functionalization and drug loading by mixing NPs with components in a suspension | In vitro: MCF-7 In vivo: tumor-bearing BALB/c mice |
↓ Amount of protein corona adsorbed on the nanocomposite ↑ Cellular uptake by MCF-7 cells↑ Hemocompatibility with only 0.1% hemolysis ↑ Toxicity against MCF-7 cells ↓ percent relative tumor volume (% RTV) in the case nanocomposite with magnetic field treatment |
| MNP-CUR [68] | Fe3O4 by coprecipitation in the presence of β-CD and F68, curcumin-loading by diffusion method | MDA-MB-231 | less aggregated nanocomposite Slow and sustained release of curcumin ↑ Drug uptake by the MDA-MB-231 cells ↑ Prevention of serum protein adsorption and colony formation ↓ Viability of MDA-MB-231 cells ↓ T2-weighted signal in MRI imaging analysis |
| Curcumin-loaded PEG/β-CD/ZnO [69] | Wet coprecipitation method | S. aureus, MCF-7 | ↑ Drug encapsulation efficiency, pH-dependent sustained drug release ↑ Antibacterial and anticancer properties compared to free curcumin ↑ Photoluminescence property compared to composite without β-CD |
| Curcumin-loaded β-cyclodextrin and pluronic F127 stabilized iron oxide (MNP–cur) [70] | Fe3O4 by Coprecipitation in the presence of β-cyclodextrin pluronic F127, curcumin-loading precipitation forms a suspension | In vitro: HPNote images cannot be edited for English. Please verify all text carefully.-II, Panc-1 A2780PC, MDA-MB-231, PC-3 In vivo: Note images cannot be edited for English. Please verify all text carefully.AF-II xenograft mice |
↑ Water dispersibility efficient drug encapsulation and sustained release ↑ MRI contrasting during MRI scanning of A2780PC ↑ Inhibition of A2780PC, MDA-MB-231 ↑ Drug uptake by HPAF-II and Panc-1 ↑Proliferation and colony formation of HPAF-II and Panc-1 ↓ Tumor growth of HPAF-II xenograft mice ↑ Serum bioavailability of curcumin (2.5× that of free curcumin) |
| Curcumin-loaded chitosan (CS)–Fe3O4 [73] | Fe3O4 by reverse microemulsion, chitosan coating by stirring together CS in acidic solution and Fe3O4 suspension in the presence of CTAB | A549 | controlled drug release profile, intact paramagnetic property, ↑ Cytotoxicity against A549 cells compared to free curcumin |
| Cur–O–CMCS–ZnO [74] | ZnO NPs using the coprecipitation method, O-CMCS coating using ex situ grafting, curcumin-loading, precipitation from solution |
MA104, L929 | ↑ Water solubility of curcumin in the composite form ↑ Accumulation and cytotoxicity towards MA104 compared to L929 |
| Curcumin-loaded, phendione-modified chitosan-coated CuO [76] | CuO by chemical reduction method, CS coating and curcumin-loading by precipitation from solutions | MCF-7, M19-MEL, HeLa | ↑ Drug loading efficiency (96.3%), sustained drug release ↑ Anticancer effect (> 2×) M19-MEL, MCF-7, HeLa compared to free curcumin |
| Curcumin-loaded, chitin–glucan-coated ZnO NPs(Cur–ChGC@ZNONPs) [78] | ChGC@ZnONPs by coprecipitation in the presence of ChGC, curcumin-loading precipitation from solution | E. coli and B. subtilis | Better inhibition effect against E. coli and B. subtilis ↑ Radical scavenging activities → increased antioxidant properties |
| Curcumin-loaded PMMA–PEG/ZnO [94] | ZnO by coprecipitation, PMMA–PEG by double emulsion, curcumin-loading and copolymer coating precipitation from suspension. | AGS | ↑ Drug loading percentage, 47% and loading efficiency, 92%, pronounced DNA fragmentation ↑ Anticancer effect compared to ZnO or curcumin |
| Curcumin-loaded, PEG-functionalized, gold nanoparticle decorated, Fe3O4–silica core–shell [81] | Coprecipitation for Fe3O4, surface modification and drug loading precipitation from solution | HL-60 | Stable composite assembly with a zeta potential of -24.5 mV ↑ T2 value during MRI imaging, ↓ Viability of HL60, 53.4% in 42 h |
| Curcumin and PAC loaded PEG-modified CeO2@SiO2 (CeO2@SiO2–PEG–PAC/Cur) [80] |
CeO2@SiO2 by chemical precipitation method, PEG by nanoprecipitation, drugs loading by precipitation from respective solutions | L02, HepG2, HeLa, PC-12 | ↓ Hydrodynamic size of the composite from 421 to 359 nm↓ Cytotoxicity towards L02, Neuroprotective effect against Aβ1-42 mediated PC-12 ↑ Antiproliferative effect against HepG2 and HeLa |
| cCur/ZnONPs [85]. | cCur/ZnO by precipitation from solution | Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Lactobacillus acidophilus (L. acidophilus) | Antibacterial growth inhibition for 90 days, ↓ bacterial growth rate after 90 days shear bond strength in acceptable range (6–8 Mpa) |
| curcumin-loaded, oleic acid, and citric acid-functionalized Fe3O4 [84] | Fe3O4 by coprecipitation, in the presence of citric acid and oleic acid, curcumin-loading by precipitation from solution | MDA-MB-231 | ↓ Viability of MDA-MB-231 compared to free curcumin treatment superparamagnetic property with saturation magnetization 60–80 emu/g ↑ T2 relaxation time→ MRI contrasting potential |
| Curcumin–ZnO incorporated carboxymethyl cellulose (Cur/ZnO/CMC) [86] | ZnO/CMC by coprecipitation in the presence of CMC, precipitation from solution | L929, MA104 | ↑ Aqueous solubility, loading efficiency of 44%, controlled release profile ↓ Cytotoxic to L929 cells (80% viability) ↑ Cytotoxicity MA104 cells (20%, viability) |
| Curcumin-loaded carboxyl-terminated ZnO NPs [88] | Coprecipitation in the presence of 3-mercaptopropionic acid (MPA), curcumin-loading precipitation from solution | MDA-MB-23 | ↑ In aqueous and ↓ In IC50 against MDA-MB-23 compared to free curcumin |
| bovine serum albumin-coated Fe3O4–curcumin (F@BSA–curcumin) [89] | Desolvation and chemical coprecipitation process | HFF2, MCF-7 | pH-dependent drug release biocompatible to HFF2 cells ↑ Cytotoxic to MCF-7 |
| Curcumin-loaded, carbon dots-coated rutile TiO2 [91] | TiO2 by coprecipitation, carbon dot coating and Curcumin-loading precipitation from solution | HaCaT, MCF-7, McCoy | ↑ Curcumin-loading percentage (89%) ↑ Inhibition of HaCaT comparable to that of the positive control 5-fluorouracil apoptosis on MCF-7, biocompatible to McCoy |
Abbreviations: ↑ = increase; ↓ = decrease; → = implies; >= greater than; MCF-7 and MDA-MB-231 = breast cancer cell lines; H9c2 = cardio myoblast cell line; PTX–cur-OAMNPPF127FA = paclitaxel and curcumin-loaded oleic acid-functionalized, pluronic F127-coated, folic acid targeted magnetic nanoparticles; Fe3O4 = superparamagnetic iron oxide; 5FU–CUR-C-MNP-HSA-FA = 5 fluorouracil and curcumin-loaded citric acid and human serum albumin-functionalized, folic acid targeted magnetic nanoparticles; HepG2 = human liver cancer cell; ALP = alkaline phosphatase; GGT = gamma glutamyl transferase; RBC = red blood cell; MG63 = postoperative tumor cells; MC3T3-E1 = mouse embryonic osteoblasts; HAPA = hydroxy apatite; β-CD = β-cyclodextrin; DOX = doxorubicin; MRI = magnetic resonance imaging; PEG = polyethylene glycol; A2780PC = ovarian cancer cell; HPAF-II and Panc-1 = human pancreatic cancer cells; A549 = adenocarcinoma human alveolar basal epithelial cells; CTAB = cetrimonium bromide; ZnO = zinc oxide; O-CMCS = O-carboxylchitosan; MA104 = cancer cells; L929 = murine fibroblast; M19-MEL = Cellosaurus cell line; CuO = copper oxide; AGS = gastric cancer cells; PMMA = poly(methyl methacrylate); HL-60 = leukemia; CeO2 = cerium oxide, SiO2 = silicon dioxide; PAC = proanthocyanidin; L02 = normal human liver cell; PC-12 = rat adrenal pheochromocytoma cell lines; CMC = carboxy methyl cellulose; IC50 = concentration that cause 50% cell density reduction; HaCaT = keratinocyte skin cells; McCoy = mouse fibroblast cells.