Porous silicon based intravitreal platform for dual-drug loading and controlled release towards synergistic therapy

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.

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Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer

Scientific Reports ◽

10.1038/s41598-020-79125-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Chao Zhang ◽

Fanghua Zhang ◽

Mengnan Han ◽

Xuming Wang ◽

Jie Du ◽

...

Keyword(s):

Breast Cancer ◽

Antitumor Activity ◽

Solid Phase ◽

Clinical Care ◽

Drug Loading ◽

Her2 Positive ◽

Apoptosis Pathway ◽

Phase Synthesis ◽

Drug Nanocarriers ◽

Dual Drug

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.

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A novel anhydrous preparation of PEG hydrogels enables high drug loading with biologics for controlled release applications

European Polymer Journal ◽

10.1016/j.eurpolymj.2021.110286 ◽

2021 ◽

Vol 147 ◽

pp. 110286

Author(s):

Christian E. Ziegler ◽

Moritz Graf ◽

Sebastian Beck ◽

Achim M. Goepferich

Keyword(s):

Controlled Release ◽

Drug Loading ◽

Peg Hydrogels ◽

High Drug ◽

High Drug Loading

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LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

New Journal of Chemistry ◽

10.1039/d1nj02159a ◽

2021 ◽

Author(s):

Yupei Ma ◽

Du Li ◽

Yunchao Xiao ◽

Zhijun OuYang ◽

Mingwu Shen ◽

...

Keyword(s):

Multidrug Resistance ◽

Cancer Cells ◽

Cancer Chemotherapy ◽

Side Effect ◽

Drug Loading ◽

Adverse Side Effect ◽

Drug Resistant ◽

Short Fibers ◽

Dual Drug

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,...

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Zirconium Based Nano Metal–Organic Framework UiO-67-NH2 with High Drug Loading for Controlled Release of Camptothecin

Journal of Inorganic and Organometallic Polymers and Materials ◽

10.1007/s10904-019-01188-y ◽

2019 ◽

Vol 30 (2) ◽

pp. 573-579

Author(s):

DaoTong Chen ◽

JiaRui Bi ◽

Jian Wu ◽

Abhinav Kumar

Keyword(s):

Controlled Release ◽

Metal Organic Framework ◽

Drug Loading ◽

High Drug ◽

Metal Organic ◽

High Drug Loading ◽

Organic Framework

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Fabrication of Porous Silicon Based Humidity Sensing Elements on Paper

Journal of Sensors ◽

10.1155/2015/927396 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Tero Jalkanen ◽

Anni Määttänen ◽

Ermei Mäkilä ◽

Jaani Tuura ◽

Martti Kaasalainen ◽

...

Keyword(s):

Porous Silicon ◽

Smart Cities ◽

Low Cost ◽

Electrical Characterization ◽

Fabrication Process ◽

Sensing Element ◽

Paper Substrate ◽

Roll To Roll ◽

Silver Electrodes ◽

Silicon Based

A roll-to-roll compatible fabrication process of porous silicon (pSi) based sensing elements for a real-time humidity monitoring is described. The sensing elements, consisting of printed interdigitated silver electrodes and a spray-coated pSi layer, were fabricated on a coated paper substrate by a two-step process. Capacitive and resistive responses of the sensing elements were examined under different concentrations of humidity. More than a three orders of magnitude reproducible decrease in resistance was measured when the relative humidity (RH) was increased from 0% to 90%. A relatively fast recovery without the need of any refreshing methods was observed with a change in RH. Humidity background signal and hysteresis arising from the paper substrate were dependent on the thickness of sensing pSi layer. Hysteresis in most optimal sensing element setup (a thick pSi layer) was still noticeable but not detrimental for the sensing. In addition to electrical characterization of sensing elements, thermal degradation and moisture adsorption properties of the paper substrate were examined in connection to the fabrication process of the silver electrodes and the moisture sensitivity of the paper. The results pave the way towards the development of low-cost humidity sensors which could be utilized, for example, in smart packaging applications or in smart cities to monitor the environment.

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Bmk9 and Uricase Nanoparticle Complex for the Treatment of Gouty Arthritis and Uric Acid Nephropathy

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3168 ◽

2021 ◽

Vol 17 (10) ◽

pp. 2071-2084

Author(s):

Tianjiao Han ◽

Meiying Wang ◽

Wenchao Li ◽

Mingxing An ◽

Hongzheng Fu

Keyword(s):

Uric Acid ◽

Drug Loading ◽

Gouty Arthritis ◽

The Body ◽

Key Points ◽

Uric Acid Nephropathy ◽

Charged Carrier ◽

Dual Drug

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.

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