Table 3.
Studies on LBNPs applied for nano-DDS formation in OC therapy.
| Nanocarrier | Active Agent | Assembly Method | Mechanism | Advantages | Ref. |
|---|---|---|---|---|---|
| Liposomes | Evodiamine (EVO) (chemotherapy drug) and ICG (PDT PS) | EI@Lipo (theragnostic nanoliposome system) encapsulated EVO, and ICG was fabricated using a typical thin-film spin evaporation process. | Chemo-antitumor effect and PDT effect of EI@Lipo encapsulating EVO and ICG and peroxidase-like catalytic activity of EVO | Theragnostic liposomes had a significant inhibitory effect on in situ tongue tumors by photodynamic combined chemotherapy. | [130] |
| DOX | Liposome-coated DOX and Doxil | Apoptotic effect on tumor cells of DOX and Doxil | Compared with DOX, Doxil had a higher apoptosis effect on CAL-27 cells, a higher elevation of caspase-3 levels, and a higher inhibition rate of C-Myc mRNA. | [131] | |
| CDDP (chemotherapy drug) and Photosan-2 (PDT PS) | Encapsulating CDDP into liposomes to form lipid-platinum-chloride NPs (LPC NPs) | Anticancer effect of CDDP and PDT effect mediated by Photosan-2 | PDT+LPC significantly reduced tumor volume. PDT+LPC or LPC treatment showed minimal side effects on renal damage compared to CDDP or the PDT+CDDP group. PDT+LPC prolonged tumor growth inhibition, thereby reducing the dose of chemotherapy drugs. | [161] | |
| DOX | Hybrid alginate/liposomes systems loading DOX | Cytotoxic effect on tumor cells of DOX | Alginate paste incorporating DOX-loaded liposomes presented similar release rates and was highly influential in promoting cancer cell death. | [162] | |
| MTX | MTX-loaded liposomes were prepared using the thin film hydration method. These liposomes were cast in the optimized mucoadhesive film to form MTX-entrapped liposomal film (M-LP-F7) | M-LP-F7 exerted a pro-oxidant effect in HSC-3 cells | Caused a significant decrease in the half-maximal inhibitory concentration of MTX on HSC-3 cells. Increased the apoptosis rate in HSC-3 cells by almost 3-fold. | [142] | |
| SLNs | HuR (ELAVL1, an RNA-binding protein) CRISPR and epirubicin | SLNs modified with pH-sensitive epidermal growth factor receptor (EGFR)-targeting and nucleus-directed peptides carrying HuR CRISPR and epirubicin | CRISPR/Cas9 suppressed proliferation, metastasis, and resistance in SAS cells. The cotreatment of epirubicin and HuR CRISPR in SAS cells further facilitated apoptosis/necroptosis/autophagy and caused cancer cell death | CRISPR/Cas9 successfully knocked out HuR and inhibited SAS cell proliferation, metastasis, and drug resistance. Epirubicin and HuR CRISPR worked together to further promote apoptosis/necrosis/autophagy of SAS cells, resulting in cancer cell death. Combined with HuR CRISPR NPs, epirubicin NPs’ anticancer effect and safety significantly improved in SAS tumor-bearing mice. | [71] |
| PTX and AA | FA-conjugated SLN loaded with PTX and AA | Cytotoxic effect of PTX and AA | Showed a biphasic drug release behavior. Had a higher efficiency when FA-conjugated PTX-loaded SLN and FA-conjugated AA-loaded SLN were combined compared to when used individually in vivo. | [58] | |
| ATRA | Phosphatidylethanolamine polyethylene glycol (PE–PEG) coated SLN loading ATRA | Chemotoxic effect of ATRA | The presence of PE–PEG improved active cell internalization of the NPs in SCC-25 cells and reduced the non-specific internalization mechanism. Delivery of ATRA into PE–PEG-coated SLNs increased their chemotoxic effect compared to non-coated SLNs. | [163] | |
| PTX, 5-FU, and AA | PTX, 5-FU, and AA entrapped SLNs | Cytotoxic effect on tumor cells of PTX, 5-FU, and AA | SLNs exhibited a biphasic nature of drug release both in vitro and in vivo. SLN loaded with PTX and SLN loaded with AA showed greater efficacy in the in vivo treatment of OSCC. | [164] | |
| NLCs | Pitavastatin (PV) and Pinus densiflora (Pd) oil | NLCs containing PV combined with Pd oil | Cytotoxicity of PV and Pd oil against HGF-1 | Had reasonable dissolution efficiency, good rheological properties, and vigorous cytotoxic activity against the HGF-1 cell line. | [132] |
| MET | MET encapsulated with NLC | Significant toxicity of GMSMET-NLCs in KB cells and an excellent inducing rise in ROS levels involved in ROS-mediated KB cell death | Achieved a MET release rate of up to 88% in 24 h. Showed significant cytotoxicity to KB OC cells with reduced IC50 values compared with the MET solution. Showed a substantial increase in intracellular ROS levels. | [133] | |
| Silymarin (SME) | SME was loaded in NLCs and further incorporated in mucoadhesive in situ gel (SME-NLCs-Plx/CP-ISG) | ROS generation potential and SME-NLCs-Plx/CP-ISG induced apoptosis at Sub-G0 phase owing to higher penetration of SME-NLCs | A sustained release effect for SMEs indicated enhanced oral mucosa retention. The IC50 value was significantly lower than that of SME-NLCs and plain SME. Had a higher inhibitory effect on human KB OC cells. | [165] | |
| QRC and piperine | QRC and piperine-enriched NLCs | Cell cycle arrest effect of QRC and piperine | Dual drug-loaded NLCs were more effective than the pure drug solution. Improved apoptosis in NLCs. Efficient distribution in various parts of the oral cavity through oral administration. | [166] | |
| HEK293T cell exosomes | MicroRNA-34a | Cholesterol-modified microRNA-34a loaded into HEK293T cell exosomes by co-incubation | MicroRNA-34a-loaded exosomes led to significant inhibition of HN6 cell proliferation, migration, and invasion by down-regulating SATB2 expression | Absorbed by HN6 oral squamous carcinoma cells and significantly inhibited the proliferation, migration, and invasion of HN6 cells by down-regulating SATB2 expression. | [134] |
| Mesenchymal stem cell-derived exosomes | MiR-155 inhibitor | MiR-155 inhibitor-laded exosomes | MiR-155 inhibitor resulted in the upregulation of FOXO3a (Forkhead box O3-, a direct target of miRNA-155) and induction of the mesenchymal-to-epithelial transition with improved sensitization to CDDP | Pinned down the stem-cell-like behavior, reversed the epithelial-to-mesenchymal transition process, and enhanced drug sensitivity through up-regulation of FOXO3a in drug-resistant xenograft OC models. | [167] |
| Exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA | siRNA of lymphocyte cytoplasmic protein 1 (LCP1) | Exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1) as octExosomes | The silencing of LCP1 by siRNA suppressed both cancer cell growth and metastatic phenotypes | Able to transfer siLCP1 stably and efficiently into OSCC cells, LCP1 was downregulated in OSCC cells with octExosomes compared to their counterparts, thus having a significant tumor-suppressor effect in vitro and in vivo. | [135] |
| Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells (hBMSCs) | miR-101-3p | HBMSCs-derived exosomes loaded with miR-101-3p | HBMSCs-exosomes combined with miR-101-3p had an excellent therapeutic effect on OC by regulating collagen type X alpha one chain (COL10A1) | Inhibited OC progression. Tumorigenicity assay in nude mice confirmed the inhibitory effects of hBMSCs-derived exosomes, loaded with miR-101-3p, on OC. | [168] |
| Milk-exosome | DOX (chemotherapy drug) and Ce6 (PDT PS) | Milk-exosomes were conjugated to DOX by a pH-cleavable bond, anthracene endoperoxide derivative (EPT1) and Ce6 were also loaded (Exo@Dox–EPT1 NPs) | Chemo-antitumor effect of DOX and PDT effect mediated by Exo@Dox–EPT1 NPs | When the NPs accumulated at the tumor site, Ce6 produced plasmonic heat and accelerated ROS generation from EPT1 under NIR irradiation. Had synergistic effects of photochemistry, which could be triggered by acid TME and NIR. | [169] |
| NE | Cur | The Cur-NE formulation was prepared according to the interfacial prepolymer deposition and spontaneous nano-emulsification method | PI3K/Akt/mTOR suppression and miR-199a upregulation mediated by Cur-Nes | Had significant dose-dependent cytotoxicity on HSC-3 cells. Down-regulated PI3K/Akt/mTOR protein expression and up-regulated PI3K-targeting miR-199a expression in a dose- or time-dependent manner. Effectively counteracted the effects of miR-199a inhibitors on OSCC cell proliferation and cell cycle proliferation phase in a time-dependent manner. | [136] |
| PLC-NPs | SAB | SAB phospholipid complex loaded NPs (nano-SAB) | The blockade of Ki-67, PCNA, and cyclin D1 expression by nano-SAB | Compared with the free-SAB-treated group and 4NQO-exposed group, nano-SAB treatment could effectively inhibit the expression of Ki-67, proliferating cell nuclear antigen (PCNA), and cyclin D1 in high-risk dysplastic lesions. After four weeks of discontinuation, nano-SAB maintained low Ki-67, PCNA, and cyclin D1 expression levels. | [137] |