Effects of Biofilm Nano-Composite Drugs OMVs-MSN-5-FU on Cervical Lymph Node Metastases From Oral Squamous Cell Carcinoma

Abstract

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin – eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes.

The application of mesoporous silica nanoparticles as a drug delivery vehicle in oral disease treatment

“…This nanoplatform of MSNs could preferentially accumulate 5-FU in tumors to suppress tumor growth and avoid side effects ( Lee et al., 2010 ; Lu et al., 2010 ). The outer membrane vesicle (OMV)-MSN-5-FU overcomes the mentioned drawbacks by reducing the cumulative drug release and prolongs the targeted action time to inhibit tumor proliferation and metastasis ( Huang et al., 2022 ). Consequently, MSNs can circumvent the challenges associated with administering anticancer medications by delivering them to specific tissues to improve biocompatibility.…”

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

“…Recent research has demonstrated the potential of inorganic NPs, including Gold NPs (AuNPs) [ 67 , 170 , 171 ], metal-organic framework (MOF) [ 60 , 73 , 172 , 173 , 174 , 175 ], mesoporous silica NPs (MSNs) [ 176 , 177 , 178 ], magnetic NPs [ 61 , 179 ], MnO 2 NPs [ 180 ], CaCO 3 NPs [ 181 ], nanoscale graphene oxide (NGO) [ 65 ], graphene quantum dots (GQDs) [ 182 ], and hydroxyapatite (HA) NPs [ 183 ] as drug delivery vehicles to deliver antitumor drugs in OC therapy ( Figure 5 ). Inorganic NPs possess unique features, such as a large surface area, small volume, ease of synthesis, molecular selective targeting, and a large area-to-volume ratio [ 5 ].…”

“…Their tunable pore structure, surface functionalization, and excellent cell internalization allow for maximum loading of small molecules and oligos [ 177 , 187 , 188 ]. Huang et al [ 176 ] prepared MSNs loaded with 5-FU (MSN-5-FU), collected the outer membrane vesicles (OMVs) of Escherichia coli to wrap MSN-5-FU, and then prepared OMVs-MSN-5-FU to explore its effect on lymph node metastasis from OSCC. The results showed that the OMVs-MSN-5-FU DDS could slow down the drug release rate, significantly inhibit OSCC cell proliferation, and control cancer cell metastasis to cervical lymph nodes.…”

“… The antitumor effect of 5-FU The OMVs-MSN-5-FU DDS could slow the drug release rate, significantly inhibit OSCC cell proliferation, and regulate cancer cell metastasis to cervical lymph nodes. [ 176 ] MTH1 inhibitor (TH287) and multi-drug resistance protein 1 (MDR1) siRNA TH287 and siRNA were loaded in a hyaluronic acid (HA)-based MSN TH287 selectively inhibited the MTH1 protein in cells and MDR1 siRNA, inhibited or suppressed the gene expression of MDR1 in the cancer cells Effectively controlled drug release and internalization in CAL-27 cells. The combination of TH287+MDR1 siRNA induced anticancer effects of tumor cells more effectively than TH287 alone.…”