scholarly journals Hyaluronic Acid-Conjugated Mesoporous Silica Nanoparticles Loaded with Dual Anticancer Agents for Chemophotodynamic Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sanghyo Park ◽  
Hyungkyu Park ◽  
Seokhyeon Jeong ◽  
Bong Gu Yi ◽  
Kyeongsoon Park ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Hyaluronic Acid ◽  
Mesoporous Silica ◽  
Cell Carcinoma ◽  
Silica Nanoparticles ◽  
Squamous Cell ◽  
Anticancer Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Therapeutic Effects

Present cancer treatments using chemotherapy are limited owing to both significant side effects to normal cells and high recurrence rates. In this study, we demonstrated cancer cell-targeting nanoparticles that load multiple anticancer agents for both specific treatments to cancer and substantial therapeutic effects. For this purpose, hyaluronic acid (HA) was conjugated to mesoporous silica nanoparticles (MSNs) for specifically targeting cancer cells. Moreover, the prepared HA-MSNs exhibited high drug loading potential and sustained drug release. Compared to bare MSNs, the HA-MSNs were internalized at an approximately three times higher rate in squamous cell carcinoma 7 (SCC7) cells. To enhance the anticancer effects of chemotherapy and photodynamic therapy (PDT), doxorubicin (DOX) and chlorin e6 (Ce6) were loaded in HA-MSNs (DOX/Ce6/HA-MSNs); the product exhibited highly effective cytotoxicity on green fluorescent protein-expressing squamous cell carcinoma 7 (SCC7) compared to the corresponding free drugs and HA-MSNs with DOX or Ce6 alone. This study indicates that the application of DOX/Ce6/HA-MSNs in chemotherapy and PDT exerts significant therapeutic effects against SCC7.

scholarly journals Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC)

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Chen ◽  
Shuzhen Zhang ◽  
Shuai Zhang ◽  
Shanjun Gao ◽  
Jianbo Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Mesoporous Silica ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Silica Nanoparticles ◽  
Squamous Cell ◽  
Mesoporous Silica Nanoparticles ◽  
Inhibitory Effect ◽  
Cell Group

AbstractHead and neck squamous cell carcinomas (HNSCC) are one of the deadliest forms of cancer, and 90% of its origin is from squamous cells. NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in squamous cell carcinoma, plays an important role in proliferation and chemoresistance. The main aims were to study the inhibitory effect of ß-lapachone (ARQ761 in clinical form) in HNSCC and to study the combinational effect of 5-FU and ß-lap in improving the therapeutic efficacy in HNSCC. Lipid bilayer–assembled mesoporous silica nanoparticles loaded with 5-FU/ß-lap were prepared and studied for its physicochemical and biological properties. ß-lap showed a concentration-dependent inhibition of NQO1 enzyme activity in Cal33 cells. Notably, significant inhibitory effect was observed at a dose of 20–50 μg/ml of ß-lap. Combination of 5-FU+ß-lap resulted in lower cell viability; most notably, 5-FU/ß-lap-loaded mesoporous silica nanoparticles (FNQ-MSN) exhibited significantly lower cell viability compared with that of any of the individual drug or physical combinations. ß-lap resulted in a decrease in the protein band of NQO1 compared with control; however, most notable decrease in the NQO1 level was observed in the FNQ-MSN-treated cell group. FNQ-MSN resulted in more than 60% of cell apoptosis (early and late apoptosis) and predominant nuclear fragmentation of cancer cells indicating the superior anticancer effect of a carrier-based combination regimen. Notable decrease in tumor volume was observed with the physical mixture of 5-FU+ß-lap; however, combined treatment of carrier-based 5-FU and ß-lap (FNQ-MSN) significantly delayed the tumor growth and prolonged the survival of tumor-bearing xenograft mice. These findings suggest the potential of NQO1 inhibitor in enhancing the chemotherapeutic potential of 5-FU in the treatment of HNSCC.

scholarly journals HOLLOW MESOPOROUS SILICA NANOPARTICLES FABRICATION FOR ANTICANCER DRUG DELIVERY

2020 ◽  
Vol 58 (1) ◽  
pp. 39 ◽  
Author(s):  
Ngoc Tram Nguyen Thi ◽  
Dai Hai Nguyen
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Anticancer Agents ◽  
Pore Volume ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
High Surface ◽  
Loading Capacity ◽  
Hollow Mesoporous Silica

Mesoporous silica nanoparticles (MSNs) have attracted significant attention from researchers thanks to their high surface area and pore volume, which can increase drug loading capacity. Moreover, MSNs, with their biocompatibility and ease of surface functionalization, are seen as potential drug delivery system. However, the loading of drug into MSNs system still needs further improvement. In this study, hollow mesoporous silica nanoparticles (HMSNs) were fabricated in order to increase the drug loading capacity of nanosilica materials. The synthesized HMSNs possessed inner hollow cores that could remarkably raise the total pore volume and thus improve the capacity for cargo loading. HMSNs were synthesized according to the hard-template method with three main steps: (1) forming of solid SiO2 nanoparticles as templates, (2) forming of core-shell structure by coating MSN layers onto the templates, and (3) forming of hollow core structure by etching away the solid template. The HMSNs product was characterized by TEM, XRD, TGA and FTIR. In addition, drug loading capacity of the material was evaluated with doxorubicin as model drug. The results indicated remarkable improvement in drug loading capacity, compared to MSN sample. Cell assays on cancer lines showed high biocompatibility. These results demonstrated the potential of HMSNs in the delivery of anticancer agents.

scholarly journals Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 (10) ◽  
pp. 4559
Author(s):  
Jinyoung Park ◽  
Yoon-Seo Jang ◽  
Jeong-Hae Choi ◽  
Miheon Ryu ◽  
Gyoo-Cheon Kim ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Nonthermal Plasma ◽  
Therapeutic Effects ◽  
Hacat Cells ◽  
Plasma Therapy

Combination therapies for the treatment of oral squamous cell carcinoma have been studied extensively and represent a synergistic approach with better outcomes than monotherapy. In this study, a novel combination therapy was investigated using gold nanoparticles (GNP) conjugated to programmed cell death protein ligand 1 (PD-L1) antibodies and nonthermal plasma (NTP). The present study describes the effectiveness of NTP using PD-L1 antibody conjugated to GNP in PD-L1 expressing SCC-25 cells, an oral squamous cell carcinoma line. Immunocytochemistry revealed higher levels of PD-L1 expression and an increase in the selective uptake of PD-L1 antibody + GNP on SCC-25 cells compared to HaCaT cells. In addition, cell viability analyses confirmed higher levels of cell death of SCC-25 cells after treatment with PD-L1 antibody, GNP, and NTP compared to HaCaT cells. Among the experimental groups, the highest cell death was observed upon treatment with PD-L1 antibody + GNP + NTP. Following the Western blot analysis and immunofluorescence staining, the expression of apoptosis-related proteins was found to increase after treatment with PD-L1 antibody + GNP + NTP among the other experimental groups. In conclusion, the treatment of SCC-25 cells with PD-L1 antibody + GNP + NTP significantly increased the number of dead cells compared to other experimental groups. The results of this in vitro study confirmed the therapeutic effects of PD-L1 antibody + GNP + NTP treatment on oral squamous cell carcinoma.

scholarly journals Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 288 ◽  
Author(s):  
Thashini Moodley ◽  
Moganavelli Singh
Keyword(s):  
Side Effects ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Therapeutic Potential ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Hek293 Cells ◽  
Cancer Drug ◽  
Delivery Vehicles

There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. The anti-cancer drug, 5-fluorouracil (5-FU), is linked to a variety of induced-systemic toxicities due to its lack of specificity and potent administration regimens, necessitating the development of delivery vehicles that can enhance its therapeutic potential, while minimizing associated side-effects. Polymeric mesoporous silica nanoparticles (MSNs) have gained popularity as delivery vehicles due to their high loading capacities, biocompatibility, and good pharmacokinetics. MSNs produced in this study were functionalized with the biocompatible polymers, chitosan, and poly(ethylene)glycol to produce monodisperse NPs of 36–65 nm, with a large surface area of 710.36 m2/g, large pore volume, diameter spanning 9.8 nm, and a favorable zeta potential allowing for stability and enhanced uptake of 5-FU. Significant drug loading (0.15–0.18 mg5FU/mgmsn), controlled release profiles (15–65%) over 72 hours, and cell specific cytotoxicity in cancer cells (Caco-2, MCF-7, and HeLa) with reduced cell viability (≥50%) over the non-cancer (HEK293) cells were established. Overall, these 5FU-MSN formulations have been shown to be safe and effective delivery systems in vitro, with potential for in vivo applications.

scholarly journals Evaluation of Hyaluronic Acid to Modulate Oral Squamous Cell Carcinoma Growth In Vitro

2020 ◽  
Vol 11 (4) ◽  
pp. 72
Author(s):  
Jordan Ringer ◽  
Bryan Morrison ◽  
Karl Kingsley
Keyword(s):  
Growth Rate ◽  
Squamous Cell Carcinoma ◽  
Hyaluronic Acid ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Chemotherapeutic Agents ◽  
Oral Tumor

Introduction: Previous studies have demonstrated that glycosaminoglycan hyaluronic acid (HA) is capable of mediating oral tumor growth. Some clinical evidence has suggested reduced HA expression predicts poor cancer prognosis and that HA-chemotherapy conjugates may function synergistically to inhibit oral tumor growth. Other studies have found conflicting results that suggest enhanced CD44-HA-mediated growth and proliferation. Due to the lack of clarity regarding HA function, the primary goal of this study was to investigate the effects of HA using well-characterized oral cancer cell lines. Methods: Using several commercially available oral squamous cell carcinoma lines (and a normal non-cancerous control), 96-well growth and viability assays were conducted using HA (alone and in combination with chemotherapeutic agents paclitaxel and PD98059). Results: Different results were observed in each of the cell lines evaluated. HA induced small, non-significant changes in cellular viability among each of the cell lines within a narrow range (1–8%), p = 0.207. However, HA induced differing effects on growth, with minimal, non-significant changes among some cell lines, such as SCC4 (+1.7%), CCL-30 (−2.8%), and SCC15 (−2.5%), p = 0.211 and more robust inhibition among other cell lines, SCC9 (−24.4%), SCC25 (−36.6%), and CAL27 (−47.8%), p = 0.0001. Differing effects were also observed with growth and viability under concomitant administration of HA with PD98059 or paclitaxel. Further analysis of these data revealed strong inverse (Pearson’s) correlations between initial baseline growth rate and responsiveness to HA administration, ranging from R = −0.27 to R = −0.883. Conclusion: The results of this study revealed differing responses to HA, which may be inversely correlated with intrinsic characteristics, such as the baseline growth rate. This may suggest that the more rapidly growing cell lines are more responsive to combination therapy with hyaluronic acid; an important finding that may provide insights into the mechanisms responsible for these observations.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Therapeutic Effects

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.

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