A Targeted and pH-Responsive Nano-Graphene Oxide Nanoparticle Loaded with Doxorubicin for Synergetic Chemo-Photothermal Therapy of Oral Squamous Cell Carcinoma

Abstract

Purpose Oral squamous cell carcinoma (OSCC) is a malignant disease with serious impacts on human health and quality of life worldwide. This disease is traditionally treated through a combination of surgery, radiotherapy, and chemotherapy. However, the efficacy of traditional treatments is hindered by systemic toxicity, limited therapeutic effects, and drug resistance. Fibroblast activation protein (FAP) is a membrane-bound protease. Although FAP has limited expression in normal adult tissues, it is highly expressed in the tumor microenvironment of many solid cancers – a characteristic that makes it an ideal target for anticancer therapy. In this study, we constructed a nano-drug delivery system (NPF@DOX) targeting FAP to increase the therapeutic efficiency of synergistic chemo-photothermal therapy against OSCC. Methods We utilized PEGylated nano-graphene oxide (NGO) to link doxorubicin (DOX) and fluorescently-labeled, FAP-targeted peptide chains via hydrogen bonding and π–π bonding to enhance the targeting capability of NPF@DOX. The synthesis of NPF@DOX was analyzed using UV–Vis and FT–IR spectroscopy and its morphology using transmission electron microscopy (TEM). Additionally, the drug uptake efficiency in vitro, photo-thermal properties, release performance, and anti-tumor effects of NPF@DOX were evaluated and further demonstrated in vivo. Results Data derived from FT–IR, UV–Vis, and TEM implied successful construction of the NPF@DOX nano-drug delivery system. Confocal laser scanning microscopy images and in vivo experiments demonstrated the targeting effects of FAP on OSCC. Furthermore, NPF@DOX exhibited a high photothermal conversion efficiency (52.48%) under near-infrared radiation. The thermogenic effect of NPF@DOX simultaneously promoted local release of DOX and apoptosis based on a pH-stimulated effect. Importantly, FAP-targeted NPF@DOX in combination with PTT showed better tumor suppression performance in vivo and in vitro than did either therapy individually. Conclusion NPF@DOX can precisely target OSCC, and combined treatment with chemical and photothermal therapy can improve the therapeutic outcomes of OSCC. This method serves as an efficient therapeutic strategy for the development of synergistic anti-tumor research.

Nano-Drug Delivery Systems in Oral Cancer Therapy: Recent Developments and Prospective

“…FAP-targeted NPF@DOX in combination with PTT demonstrated better tumor suppression performance than either therapy alone. [ 76 ] ZIF-8 nanostructures composed of Zn(NO 3 ) 2 ·6H 2 O and 2-methylimidazole DOX MOFs coated with dental pulp mesenchymal stem cell (DPSC) membranes contained CXCR2 carried DOX to form MOF-DOX@DPSCM Killing activity and induced apoptotic effect of MOFDOX@DPSCM and specific targeting effect of DPSC membranes MOF@DPSCM was specific to OSCC and could induce CAL-27 cell death in vitro and block CAL-27 tumor growth in vivo. [ 73 ] Zinc-based MOFs (Zn 4 O(C 8 H 5 NO 4 ) 3 , IRMOF-3) DOX and celecoxib (Cel) MOFs were integrated with thermosensitive hydrogels to devise an injectable implant, and DOX Cel was coloaded into the system (DOX/Cel/ MOFs@Gel) Toxic effects against OC cells of DOX and Cel Exhibited a high capacity for drug loading, stable and pH-responsive release of dual drugs, and enhanced toxic effects on KB and SCC-9 cells in vitro.…”

“…FA receptor [56][57][58][59][60][61][62] Protein corona-modulating Tf2 peptide Transferrin receptor (TfR) [63] HN-1, a 12-amino acid peptide HN-1 receptor [64,65] Anti Programmed death-ligand 1 (PD-L1) antibody PD-L1 [66,67] α-tocopherol α-tocopherol receptor [68] Fucoidan Scavenger-A receptors (SR-A), L-selectin, Toll-like receptors, and PD-L1 [69] Antibodies specific for matrix metalloproteinase-1 (MMP-1) MMP-1 [70] pH-sensitive H-peptide Epidermal growth factor receptor (EGFR) [71] Anti-Her-2 (human epidermal growth factor receptor 2) nanobody Her-2 [72] Dental pulp mesenchymal stem cell (DPSC), which expresses the CXCL8 binding receptor, CXCR2 Chemokine CXCL8 [73] Chemokine SDF-1 CXC chemokine receptor 4 (CXCR4) [74] Shiga Toxin-B Globotriaosylceramide receptor (GB3) [75] Fibroblast activation protein (FAP)-targeted peptide chains FAP [76] AE105 (H-Asp-Cha-Phe-(d)Ser-(d)Arg-Tyr-Leu-Trp-SerOH) peptide Urokinase plasminogen activator receptor (uPAR) [77]…”

Polydopamine-Based Nanoparticles for Synergistic Chemotherapy of Prostate Cancer

“…In recent years, the combination of immunotherapy and chemotherapy has become a hot topic in solid tumor research. Doxorubicin (DOX) is a well-known anticancer drug used to treat various cancers, 3 , 4 but DOX can also cause upregulation of PD-L1 expression in tumor cells, leading to T cell inactivation through the PD-1/PD-L1 pathway. 5 , 6 Meanwhile, DOX is prone to serious toxic side effects and is easily cleared by the liver or kidneys, greatly reducing the therapeutic effect on tumors.…”