Table 1.
Recent experimental (in vitro and in vivo) investigations highlighting the therapeutic potential of inorganic NDDPs for treatment of various cancers.
| NDDP | Inorganic Agent(s) | Ther. Agent | DLC/DRE (%) | Stimuli | Study Model | Cancer Type | Preventive Outcomes of NDDPs in Cancer |
|---|---|---|---|---|---|---|---|
| nGO-DOX-cPEG [6] | Graphene | DOX | ~70/>60 | NIR, pH | In vitro: PC3, DU145, LNCaP In vivo: BALB/c nude |
Prostate | In vitro: ↑ cancer cells killing by ~80%, ↑ cellular drug uptake, ↑ apoptotic effects (higher expression of p53, p21, bax, c-caspase 3). ↓ cytotoxicity for normal cells. In vivo: ↑ site selective accumulation and prolong blood circulation (>24 h), ↑ sustained drug release and retention. ↓ tumor growth and volume. |
| HSG-DOX [7] | Graphene | DOX | 49.2/>50 | NIR, Redox | In vitro: MDA-MB-231 In vivo: BALB/c nude |
Breast | In vitro: ↑ targeted delivery to HA-receptor over expressing tumors, ↑ endo/lysosomal escape, ↑ cytoplasmic release. ↓ cytotoxic even at <10 µg mL−1. In vivo: ↑ preferential accumulation (36 h) and tumor targeting, ↑ sustained drug release and retention. ↓ tumor growth and volume, ↓ side effects (evidenced by improvements in body weight). |
| GO-CHI-HA-SNX-2112 [8] | Graphene | SNX-2112 | >110/>40 | pH | In vitro: A549, NHBE In vivo: Sprague-Dawley |
Lung | In vitro: ↑ CD44 receptor mediated cellular uptake and intracellular drug distribution, ↑ cell apoptosis as high as 36.59%, ↑ blood compatibility (haemolysis analysis). ↓ cytotoxic (evidenced by cell viability). In vivo: ↑ immune-tolerant, ↓ tissue swelling, inflammation and lesion formation, ↓ necrocytosis and fibrous proliferation, ↓ systemic side effects. |
| DOX-FA-rGO/ZnS:Mn [9] | Graphene, Zinc, Manganese | DOX | ~35/95 | pH | In vitro: MDA-MB-231, NIH-3T3 In vivo: NS |
Breast | In vitro: ↓ cancer cells viability by 50%, FA functionalization decreased the toxic response up to 72 h, FA functionalized system further improved the drug disperseability, bioavailability and selective drug release. In vivo: NS |
| H-MnO2-PEG-C&D [10] | Manganese | Ce6, DOX | >86/>90 | pH, NIR | In vitro: 4T1 In vivo: Balb/c mice |
Breast | In vitro: relieve tumor hypoxia, ↓ high photo-toxicity for cancer cells, ↑ intracellular accumulation, ↑ killing cancer. In vivo: ↑ efficient tumor accumulation, ↑ decomposition of H2O2 into O2 and accumulation tumor, ↓ reduce tumor hypoxia, ↓ tumor size, ↓ side effects (evidenced by improvements in body weight), ↑ macrophages infiltration, ↑ cytotoxic T lymphocytes, ↑ TNF-α secretion |
| DOX-PVP-AuNPs [11] | Gold | DOX | NR/91 | pH | In vitro: 549, H460, H540 In vivo: NS |
Lung | In vitro: ↑ inhibition of lung cancer cells proliferation, ↑ ROS generation, ↑ cancer cell apoptosis, ↑ mitochondrial membrane depolarization potential (more cellular uptake), ↑ expression of apoptotic cytochrome oxidase C and bax, ↑ expression of tumor suppressing p21, p53, ↑ expression of caspases 3 and 9. In vivo: NS |
| BLM-DOX-PEG-AuNPs [12] | Gold | BLM, DOX | 33/2.3 | pH | In vitro: HeLa In vivo: NS |
Ovarian | In vitro: ↑ cytotoxicity for cancerous cells at lower concentration, ↑ active targeting, ↑ cancer cell apoptosis, ↑EC50 values. ↓ agglomeration. In vivo: NS |
| Se-Au-mSiO2-DOX [13] | Gold, Selenium, Silicon | DOX | 8.1/80 | Laser NIR | In vitro: MCF-7, MDA-MB-231 In vivo: BALB/c nude |
Breast | In vitro: ↑ reversing multidrug resistance strategy, ↑ intracellular drug release in lysosomes, ↑ cytotoxic effect and cancer cells killing (evidenced by cell shrinkage, chromatin condensation, degeneration, nuclear fragmentation), ↑ apoptosis (~40% of cells in late apoptosis), ↑ ROS generated mediated mitochondrial dysfunction, ↑ expression of tumor suppressing p21, p53, ↑ Bid and Bad expression. ↓ GSH/GSSG ratio, ↓ PARP expression, ↓ Bcl-xl expression, ↓ Src/FAK/AKT pathways. In vivo: ↑ nanoparticles accumulation in tumor sites (24 h), ↑ cellular apoptosis by 10 fold, ↑ caspase 3 by 11 fold, ↑ PARP by 13 fold. ↓ tumor progression, ↓ tumor volume by 5 fold, ↓ adverse effects. |
| Ag-GQDs-DOX [14] | Silver | DOX | NR/NR | pH | In vitro: DU145, HeLa In vivo: NS |
Prostate, Cervical | In vitro: ↑ antitumor activity, ↑ apoptosis in cancer cells, ↓ affecting the viability of normal cells, ↑ caspase-3 activity, ↑ caspase-7 activity, ↑ cellular drug uptake. In vivo: NS |
| CPT-CEF [15] | Iron | CPT | NR/65 | pH, Temp. | In vitro: HT29, A549 In vivo: NS |
Colon, Lung | In vitro: ↓ cancer cells viability, ↑ membrane rupturing and nuclear fragmentation, ↑ induction of cell toxicity cancer cells, ↑ early apoptosis, ↓ cancer cells proliferation, ↑ mitochondrial membrane depolarization, ↑ caspase-3 activity. In vivo: NS |
| HA-FeOOH-PPy NRs [16] | Iron | HA | NR/NR | Laser | In vitro: MDA-MB-231 In vivo: BALB/c nude |
Breast | In vitro: ↓ cancer cells viability, ↑ quick cellular uptake, ↑ selectivity toward CD44 expressing cancer cells, ↑ biocompatible, ↑ cancer cells killing efficiency, ↑ localized drug distribution around the tumor. In vivo: ↑ tumor volume growth (by 11 times), ↓ side effects (evidenced by improvements in body weight). |
| MNP-HC [17] | Iron | TZ | NR/NR | NS | In vitro: SKBR3, MDA-MB-231 In vivo: NS |
Breast | In vitro: ↑ up to 97% binding to the tested cell lines, ↑ site-specific phosphorylation in catalytic domain of HER2, ↑ cellular uptake, ↑ anti-cancer proliferative effect (antibody dependent cell mediated cytotoxicity) by 41.8%, ↑ p27kip1 expression. In vivo: NS |
| DOX-MGNSs [18] | Iron, Gold, Silica | DOX | 65.8/86.2 | pH, Temp. | In vitro: ATCC CCL-2 In vivo: NS |
Ovarian | In vitro: ↑ cytoxicity for cancer cells, ↑ cellular uptake, ↑ anti-cancer proliferative effect, ↑ disruption of ruffles in cells (loss of morphology). In vivo: NS |
| HA-ionic-TPP-DOX [19] | Phosphonium | DOX | 31.4/91 | pH | In vitro: MCF-7/ADR In vivo: BALB/c nude, Tg(fli1a:eGFP)+/− |
Breast | In vitro: ↑ cellular uptake and cytoxicity in tumor cells, ↑ prolong blood circulation, ↑ drug distribution in tumors, ↑ enhanced permeability and retention, punctate distribution (selectively mitochondrial accumulation), ↑ ROS generation. In vivo: ↑ tumor targeting, ↓ tumor growth and tumor progression, ↓ tumor volume, ↓ adverse effects (cardiotoxicity). |
| DOX-BP-Hyd [20] | Phosphorus | DOX | NR/38.8 | NIR, Light | In vitro: MDA-MB-231, A549, HeLa, B16 In vivo: BALB/c nude |
Breast, Lung, Cervical, Melanoma | In vitro: ↑ cell killing ability, ↑ tumor ablation effect, ↑ biodegradability, ↑ biosafety. In vivo: ↑ localized drug distribution around the tumor site, ↑ sustained release (<12 h), ↓ tumor growth and volume, ↓ acute side effects (evidenced by improvements in body weight), ↓ toxic to normal tissues. |
NDDPs: nano-drug delivery platforms; Ther.: therapeutic; DLC/DRE: drug loading capacity and drug release efficiency; ↑: increased/improved/higher/more/upregulate; ↓: reduced/decreased/lower/less/downregulate; DOX: doxorubicin; nGO-DOX-cPEG: DOX incorporated lateral nanodimentional graphene oxide chitosan polyethylene glycol flakes; NIR: near-infrared; p21: cyclin dependent inhibitor kinase 1; p53: tumor protein 52; bax: BCL2 associated X; h: hours; HSG-DOX: DOX incorporated in bioreducible hyaluronic acid graphene oxide nanosheets; GO-CHI-HA-SNX-2112: SNX-122 incorporated in chitosan modified graphene oxide nanocomposites; NHBEs: normal human bronchial epithelial cells; DOX-FA-rGO/ZnS:Mn: DOX incorporated in reduced graphene oxide manganese doped zinc sulfide quantum dots functionalized with folic acid functionalized; NS: not studied; FA: folic acid; H-MnO2-PEG-C&D: Ce6 and DOX incorporated in hollow manganese oxide nanoshells functionalized polyethylene glycol; Ce6: chlorine e6; DOX-PVP-AuNPs: DOX incorporated in polyvinylpyrrolidone stabilized gold nanoparticles; NR: not reported; ROS: reactive oxygen species; BLM-DOX-PEG-AuNPs: BLM and DOX incorporated in polyethylene glycolated gold nanoparticles; BLM: bleomycin; Se-Au-mSiO2-DOX: DOX incorporated in nanoselenium over coated mesoporous silica capped gold nanorods; GSH/GSSG: glutathione/oxidized glutathione; PARP: poly ADP ribose polymerase; Bcl-xl: B-cell lymphoma extra-large; Src/FAK: steroid receptor coactivator/focal adhesion kinase; Ag-GQDs-DOX: DOX incorporated in PEGylated silver nanoparticles decorated with graphene quantum dots; CPT-CEF: CPT incorporated in a composite nanoparticle of magnetic iron oxide (Fe3O4) and β-cyclodextrin cross-linked with ethylenediaminetetraacetic acid (EDTA); CPT: Camptothecin; HA-FeOOH-PPy NRs: hyaluronan coated FeOOH@polypyrrole nanorods; HA: hyaluronan; HA-ionic-TPP-DOX: DOX incorporated in triphenylphosphonium (linked to hyaluronic acid by ionic bond) supra-molecular self-assembled structures; Tg(fli1a:eGFP)+/−: Transgenic zebrafish; DOX-BP-Hyd: DOX incorporated in nanocomposite of black phosphorus nanosheets and hydrogel; MNP-HC: half chain trastuzumab incorporated in magnetic iron oxide nanoparticles (MNP-HC); TZ: trastuzumab; HER2: human epidermal growth factor receptor 2; p27Kip1: cyclin-dependent kinase inhibitor p27Kip1; DOX-MGNSs: DOX incorporated in ma/gnetic and gold nanoparticles embedded silica nanoshuttles; Temp: temperature.