Therefore, designing theranostic systems containing both imaging and anticancer agents will significantly improve the diagnosis and treatment of OSCC at early stages. 5. developed as alternative methods aiming to enhance the benefits of the current anticancer therapies, while minimizing their undesirable toxic effects on the healthy non-cancerous cells. Targeted drug delivery systems have the potential to increase drug bioavailability and bio-distribution at the site of the primary tumour. This review confers current knowledge on the diverse drug delivery methods, potential carriers (e.g., polymeric, inorganic, and combinational nanoparticles; nanolipids; hydrogels; exosomes) and anticancer targeted approaches for oral squamous cell carcinoma treatment, with an emphasis on their clinical relevance in the era of precision medicine, circadian chronobiology and patient-centred health care. tongue/sublingual (= 10); gingiva of the mandible (= 1); gingiva or the maxilla (= 2)Intratumoral injection of radioactive agentsIn vivoEight male and five female cats[165]Injection of drug loaded gels into tumors (up to 6 weeks treatments), at dosage: 0.25 mL of active or placebo gel per cm3 of the BMS-663068 (Fostemsavir) tumor up to 10 mL total The tumor response noted in 29% of patients, including 19% cases with complete responses in the drug-loaded gel group versus 2% for placebo ( 0.001). Purified bovine collagen/gelCisplatin/EpinephrineHead and neck tumorsIntratumoralClinical study (178 patients pretreated with recurrent or refractory HNSCC); prospective, double-blind placebo-controlled phase III trialsMale and female humans[147]SAHA and DDP were loaded into a biodegradable and thermosensitive hydrogel (PECE) Mice treated with SAHA-DDP/PECE had the smallest tumor volume (62.43 mm3) compared to other groups tumor volume. PECECisplatin (DDP)/SAHAIn vitro: HSC-3 and HOK16-E6E7 cells. br / In vivo: 2 106 HSC-3 cells were injected subcutaneously into the right flank regionsIntratumoralIn vitro and in vivoFemale mice[137]Synthesizing DTX encapsulated PLGA nanoparticles for in situ delivery to the tumor site The slow release profile of the drug (60% of DTX released in 9 days) Higher cytotoxic effect against SCC-9 cells compared to free drug PLGADocetaxel (DTX)Human tongue squamous carcinoma derived cell line SCC-9IntratumoralIn vitroN/A[166]Irradiation following intra-tumoral injection of gold nanorods (GNRs) conjugated with rose bengal (RB) The tumor inhibition BMS-663068 (Fostemsavir) rate was significant (95.5%) on the 10th day after treatment for (f). Gold nanorods (GNRs)/Rose Bengal-Tumors induced in hamster cheek pouchesIntratumoral combined with photo-dynamic (PDT) and photothermal (PTT) br / therapy In vitro and in vivoMale hamsters[167] Synthesizing and drug encapsulation of EA loaded chitosan nanoparticles Sustain drug release by 48 h Decreased proliferation of BMS-663068 (Fostemsavir) human oral cancer KB cell lines (in vitro) ChitosanEllagic acid (EA)Human oral cancer KB cell linelocalIn vitroN/A[108]Curcumin-loaded in PCL nanoparticles and coated with chitosan as a mucoadhesive polymer Reduced viability of SCC-9 BMS-663068 (Fostemsavir) human oral cancer cell line Decreased toxicity of curcumin incorporated in nanoparticles compared to its free state ChitosanCurcuminSCC-9 human oral squamous carcinoma cell; for permeation studies: esophageal mucosa of at least two different animalslocalIn vitroN/A[104] Nano-emulsions loaded with Gen and coated with chitosan in BMS-663068 (Fostemsavir) the form of tablets Controlled release profile Anticancer activity against two oropharyngeal carcinoma-derived cell lines Both formulations showed equivalent cell kill ratio within 48 h Nanoemulsion, chitosan, cellulose microcrystalline, dextrose Genistein (Gen)SCC-4 cells, FaDu cells, and murine connective tissue fibroblasts (L929) (in vitro)/ br / porcine buccal Mucosa (ex vivo)localIn vitro and ex vivoN/A[168]Using MTX loaded liposomes to prepare the mucoadhesive film Increased apoptosis rate in HSC-3 cells by three fold in M-LP-F7 The pro-oxidant effect in HSC-3 cells by M-LP-F7 Liposomes, chitosan (CH), poly(vinyl alcohol) (PVA), hydroxypropyl methylcellulose (HPMC)Methotrexate (MTX)HSC-3 cellslocalIn vitroN/A[169]Preparation of a targeted nanoparticle platform combing Pc 4 with IO and a cancer targeting ligand, then intravenous injection of non-formulated Pc4 and two nanoparticle formulations: targeted (Fmp-IO-Pc4) and non-targeted (IO-Pc4) were administered to mice Significant tumor inhibition in both Fmp-IO-Pc4 and IO-Pc4 compared to free Pc4 Significant reduction in tumor volume in targeted nanoparticles (Fmp-IO-Pc 4) compared to IO-Pc4 Iron oxide (IO) nanoparticlesPDT drug (Pc 4)In vitro: M4E, M4E-15, 686LN, and TU212 cell linesPDT In vitro and in vivoFemale mice[170]Preparation of gold nanoparticles conjugated with anti-EGFR antibody, then evaluation of the effect of PDT combined with Hs.76067 administration of anti-EGFR antibody conjugated Au nanoparticles on two OSCC lines and one epithelial cell line No photothermal destruction was seen.