Utilizing the protein corona around silica nanoparticles for dual drug loading and release

Nanoscale ◽  
2015 ◽  
Vol 7 (39) ◽  
pp. 16251-16265 ◽  
Author(s):  
Shakiba Shahabi ◽  
Laura Treccani ◽  
Ralf Dringen ◽  
Kurosch Rezwan

The protein corona, which forms spontaneously around silica nanoparticles in serum-containing media, can be exploited for delivery of multiple drugs.

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1254
Author(s):  
Lingjie Ke ◽  
Zhiguo Li ◽  
Xiaoshan Fan ◽  
Xian Jun Loh ◽  
Hongwei Cheng ◽  
...  

Drug resistance always reduces the efficacy of chemotherapy, and the classical mechanisms of drug resistance include drug pump efflux and anti-apoptosis mediators-mediated non-pump resistance. In addition, the amphiphilic polymeric micelles with good biocompatibility and high stability have been proven to deliver the drug molecules inside the cavity into the cell membrane regardless of the efflux of the cell membrane pump. We designed a cyclodextrin (CD)-based polymeric complex to deliver chemotherapeutic doxorubicin (DOX) and Nur77ΔDBD gene for combating pumps and non-pump resistance simultaneously. The natural cavity structure of the polymeric complex, which was comprised with β-cyclodextrin-graft-(poly(ε-caprolactone)-adamantly (β-CD-PCL-AD) and β-cyclodextrin-graft-(poly(ε-caprolactone)-poly(2-(dimethylamino) ethyl methacrylate) (β-CD-PCL-PDMAEMA), can achieve the efficient drug loading and delivery to overcome pump drug resistance. The excellent Nur77ΔDBD gene delivery can reverse Bcl-2 from the tumor protector to killer for inhibiting non-pump resistance. The presence of terminal adamantyl (AD) could insert into the cavity of β-CD-PCL-PDMAEMA via host-guest interaction, and the releasing rate of polymeric inclusion complex was higher than that of the individual β-CD-PCL-PDMAEMA. The polymeric inclusion complex can efficiently deliver the Nur77ΔDBD gene than polyethylenimine (PEI-25k), which is a golden standard for nonviral vector gene delivery. The higher transfection efficacy, rapid DOX cellular uptake, and significant synergetic tumor cell viability inhibition were achieved in a pump and non-pump drug resistance cell model. The combined strategy with dual drug resistance mechanisms holds great potential to combat drug-resistant cancer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Zhang ◽  
Fanghua Zhang ◽  
Mengnan Han ◽  
Xuming Wang ◽  
Jie Du ◽  
...  

AbstractCombination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2+ cancer.


2021 ◽  
Author(s):  
Yupei Ma ◽  
Du Li ◽  
Yunchao Xiao ◽  
Zhijun OuYang ◽  
Mingwu Shen ◽  
...  

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...


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.


Nanoscale ◽  
2013 ◽  
Vol 5 (14) ◽  
pp. 6372 ◽  
Author(s):  
Ninell P. Mortensen ◽  
Gregory B. Hurst ◽  
Wei Wang ◽  
Carmen M. Foster ◽  
Prakash D. Nallathamby ◽  
...  

2021 ◽  
Vol 17 (10) ◽  
pp. 2071-2084
Author(s):  
Tianjiao Han ◽  
Meiying Wang ◽  
Wenchao Li ◽  
Mingxing An ◽  
Hongzheng Fu

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.


Materials ◽  
2019 ◽  
Vol 12 (19) ◽  
pp. 3202
Author(s):  
Sumita Swar ◽  
Veronika Máková ◽  
Ivan Stibor

Our study was focused on the synthesis of selective mesoporous silica nanoparticles (MSNs: MCM-41, MCM-48, SBA-15, PHTS, MCF) that are widely studied for drug delivery. The resulting mesoporous surfaces were conveniently prepared making use of verified synthetic procedures. The MSNs thus obtained were characterized by Brunauer-Emmett-Teller (BET) analysis and scanning electron microscopy (SEM). The selected MSNs with various pore diameters and morphologies were examined to evaluate the capability of L-DOPA drug loading and release. L-DOPA is a well-known drug for Parkinson’s disease. The L-DOPA drug loading and release profiles were measured by UV-VIS spectroscopy and SBA-15 was proved to be the most effective amongst all the different types of tested mesoporous silica materials as L-DOPA drug vehicle.


Nanoscale ◽  
2020 ◽  
Vol 12 (25) ◽  
pp. 13637-13653 ◽  
Author(s):  
Xia Chen ◽  
Shuang Zhu ◽  
Xisu Hu ◽  
Dayu Sun ◽  
Junling Yang ◽  
...  

It aims to explore the toxicity and mechanism of large-surface-area MSiNPs and MSiNPs-Ag+ exposed to hCEC cells and cornea. A protein corona-based therapy was proposed to treat MSiNPs and MSiNPs-Ag+ induced corneal damage and dry eye.


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