Erythrocyte-cancer hybrid membrane-camouflaged mesoporous silica nanoparticles loaded with Gboxin for glioma-targeting therapy

Author(s):  
Xiuxiu Jiao ◽  
Xiaoyan Yu ◽  
Chunai Gong ◽  
Hao Zhu ◽  
Bin Zhang ◽  
...  

Objective: The purpose of this research is to formulate a biomimetic drug delivery system that can selectively target glioblastoma (GBM) to deliver the antitumor agent, Gboxin: a novel Complex V inhibitor. Gboxin can specifically inhibit GBM cell growth but not normal cells. Methods: In the present study, we utilized Red Blood Cell (RBC) membrane and U251 cell membrane to obtain a hybrid biomimetic membrane (RBC-U), and prepared RBC-U coated Gboxin-loaded mesoporous silica nanoparticles ((MSNs/Gboxin)@[RBC-U]) for GBM chemotherapy. The zeta potential, particle size, and morphology of (MSNs/Gboxin)@[RBC-U] were characterized. The cellular uptake, effect of cells growth inhibition, biocompatibility, and specific self-recognition of nanoparticles were evaluated. Results: The (MSNs/Gboxin)@[RBC-U] was successfully fabricated and possessed high stability in the circulation system. The drug loading of Gboxin was 13.9%. (MSNs/Gboxin)@[RBC-U], effectively retain drugs in the physiological environment and releasing Gboxin rapidly in the tumor cells. Compared to the MSNs/Gboxin, the (MSNs/Gboxin)@[RBC-U] exhibited highly specific self-recognition to the source cell line. Additionally, the (MSNs/Gboxin)@[RBC-U] showed excellent anti-proliferation efficiency (IC50 = 0.21 μg/mL) in the tumor cell model and a few side effects in normal cells in vitro. Conclusion: The (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effects in vitro and the specific self-recognition to GBM cells. Hence, (MSNs/Gboxin)@[RBC-U] could be a promising delivery system for GBM targeted therapy.

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 288 ◽  
Author(s):  
Thashini Moodley ◽  
Moganavelli Singh

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Weibin Zhang ◽  
Chunhua Zhu ◽  
Fangnan Xiao ◽  
Xiaodong Liu ◽  
Anhua Xie ◽  
...  

The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.


2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Mingwei He ◽  
Zainen Qin ◽  
Xiaonan Liang ◽  
Xixi He ◽  
Bikang Zhu ◽  
...  

Abstract Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.


2021 ◽  
Vol 11 (13) ◽  
pp. 6121
Author(s):  
Candace M. Day ◽  
Martin J. Sweetman ◽  
Yunmei Song ◽  
Sally E. Plush ◽  
Sanjay Garg

Functionalized nanoparticles have played a major role in the field of targeted therapy, owing to their ability to control the release and for the selective delivery of entrapped materials to tumours. In this work, we described the loading capacity and in vitro release kinetics of mesoporous silica nanoparticles (MSNs), functionalized with Poly-L-Histidine and Tamoxifen. The model drug Doxorubicin (DOX) was successfully encapsulated into MSN-based systems, using the technique of solvent immersion. A post-surface grafting loading method was investigated on functionalized systems, with DOX loading content determined using HPLC. Dialysis bag diffusion was employed to investigate the release kinetics of DOX-loaded-systems at pH 7.4 and 5. The amount of DOX released from native MSNs systems over a 72 h period at pH 5 was approximately 40%; and at pH 7.4 ≈ 30%. A moderate pH dependent release behaviour was observed with both our functionalized systems: DOX@MSN-PLH and DOX@MSN-PLH-TAM; with approximately 5% of DOX released from DOX@MSN-PLH-TAM at pH 7.4 and about 9% released at pH 7.4 over 72 h. The maximal cumulated release of DOX molecules from DOX@MSN-PLH after 72 h was ≈ 18% at pH 7.4 and ≈ 23% at pH 5, respectively. The outcome of this work offers a promising contribution towards building future stimuli-responsive nano-drug delivery systems.


2013 ◽  
Vol 829 ◽  
pp. 251-257 ◽  
Author(s):  
Abdollah Zakeri Siavashani ◽  
Masoume Haghbin Nazarpak ◽  
Fateme Fayyaz Bakhsh ◽  
Tayebeh Toliyat ◽  
Mehran Solati-Hashjin

This study has focused on mesoporous silica nanoparticles as a drug delivery system of insulin, which was synthesized via a hydrothermal process. The morphology and composition of the silica nanoparticles were characterized by different analytical techniques such as Scanning Electron Microscope (SEM), X-Ray Diffraction Analysis (XRD), Fourier Transform Infrared spectroscopy (FTIR) and BrunauerEmmettTeller (BET). The percentage of drug loading and the in vitro drug release properties of the mesoporous silica nanoparticles in gastrointestinal tract were investigated in simulated gastrointestinal conditions by ultraviolet-visible spectroscopy. The results showed the amorphous structure of SBA-15 in mesoporous silica particles has a narrow pore size distribution. Also, particles shape was nearly wheat-like with almost homogeneous size distribution. Furthermore, it was revealed that the mesoporous silica nanoparticles have a high insulin loading and release capacity. These prominent behaviors make mesoporous silica nanoparticles promising material as a drug carrier for insulin delivery.


Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3337
Author(s):  
Sara Hooshmand ◽  
Sahar Mollazadeh ◽  
Negar Akrami ◽  
Mehrnoosh Ghanad ◽  
Ahmed El-Fiqi ◽  
...  

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.


2018 ◽  
Vol 6 (39) ◽  
pp. 6269-6277 ◽  
Author(s):  
Yaya Cheng ◽  
Xiangyu Jiao ◽  
Liang Zhao ◽  
Yang Liu ◽  
Fang Wang ◽  
...  

Inspired by aquaporins in nature, herein, a biomimetic free-blocking on-demand drug delivery system is proposed, which is constructed by controlling the wettability of the inner surface of nanochannels on mesoporous silica nanoparticles (MSNs).


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3321
Author(s):  
Etienne J. Slapak ◽  
Lily Kong ◽  
Mouad el Mandili ◽  
Rienk Nieuwland ◽  
Alexander Kros ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system. To this end, we developed a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSN) functionalized with an avidin–biotin gatekeeper system containing a protease linker that is specifically cleaved by tumor cells. Bioinformatic analysis identified ADAM9 as a PDAC-enriched protease, and PDAC cell-derived conditioned medium efficiently cleaved protease linkers containing ADAM9 substrates. Cleavage was PDAC specific as conditioned medium from leukocytes was unable to cleave the ADAM9 substrate. Protease linker-functionalized MSNs were efficiently capped with avidin, and cap removal was confirmed to occur in the presence of PDAC cell-derived ADAM9. Subsequent treatment of PDAC cells in vitro with paclitaxel-loaded MSNs indeed showed high cytotoxicity, whereas no cell death was observed in white blood cell-derived cell lines, confirming efficacy of the nanoparticle-mediated drug delivery system. Taken together, this research introduces a novel ADAM9-responsive, protease-dependent, drug delivery system for PDAC as a promising tool to reduce the cytotoxicity of systemic chemotherapy.


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