Development of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy

Liver cancer has a high incidence and a poor prognosis, which seriously affects human health. Doxorubicin is one of the chemotherapeutics used in the treatment of tumours, but its severe adverse reactions, especially cardiac toxicity, have limited its clinical application. The nanometre drug delivery system enables drug-loaded nanoparticles to be specifically concentrated in tumour tissues, increasing cell uptake and improving curative effect. Therefore, in this paper, folic acid-modified mesoporous silica nanoparticles (MSN-NH2-PEG-FA) were synthesized by modifying the folic acid on the surface of a drug carrier by using the characteristics of the expression of folic acid receptors, and using it as a drug. The carrier was loaded with antitumor drug doxorubicin hydrochloride (DOX), and a nanometre drug delivery system (MSN-NH2-PEG-FA/DOX) was constructed. At the same time, the near-infrared dye Cy5 was used to mark the mother nucleus to construct fluorescent nanoparticles (MSN-NH2-PEG-FA/DOX-Cy5) for cell and tumour imaging, so as to obtain the abdominal image of liver cancer patients, thereby realizing diagnosis and treatment. The research results show that the carrier can specifically gather in the liver area, reduce the distribution in the heart, reduce the toxic and side effects of drugs, and prolong the survival time of patients. The results of this study provide new ideas for the treatment of liver cancer, and provide a new theoretical basis and experimental basis for the study of inorganic nanomaterials as targeted drug delivery systems.

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Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment

Journal of Controlled Release ◽

10.1016/j.jconrel.2015.06.035 ◽

2015 ◽

Vol 214 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Karsten Voss ◽

Karen Falke ◽

Arne Bernsdorf ◽

Niels Grabow ◽

Christian Kastner ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Injectable Drug ◽

Glaucoma Treatment

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Radiation synthesis and characterization of sodium alginate/chitosan/hydroxyapatite nanocomposite hydrogels: a drug delivery system for liver cancer

Polymer Bulletin ◽

10.1007/s00289-015-1301-z ◽

2015 ◽

Vol 72 (4) ◽

pp. 725-742 ◽

Cited By ~ 36

Author(s):

Manal F. Abou Taleb ◽

Abdullah Alkahtani ◽

Sahar K. Mohamed

Keyword(s):

Drug Delivery ◽

Liver Cancer ◽

Sodium Alginate ◽

Drug Delivery System ◽

Delivery System ◽

Synthesis And Characterization ◽

Radiation Synthesis ◽

Nanocomposite Hydrogels

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Novel Dual CAFs and Cancer Cell Targeting Nano-Drug Delivery System for Anti-Fibrosis Mechanism of Liver Cancer

10.21203/rs.3.rs-842109/v1 ◽

2021 ◽

Author(s):

Chunjing Guo ◽

Xiaoya Hou ◽

Xue Liu ◽

Changgang Sun ◽

Daquan Chen ◽

...

Keyword(s):

Drug Delivery ◽

Hyaluronic Acid ◽

Liver Cancer ◽

Tumor Cell ◽

Drug Delivery System ◽

Delivery System ◽

In Vitro Release ◽

Deep Penetration ◽

Therapeutic Effects ◽

Dual Targeting

Abstract This study proposed the construction of a delivery system based on dual targeting cancer-associated fibroblasts (CAFs) and tumor cell for the treatment of liver cancer. (Z-Glycine-Proline)-Hyaluronic Acid-Sulcanidone-Ginger Anone, named as GHSO, was an amphiphilic carrier material with dual pH/ROS sensitive and dual targeting properties that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Consequently, we combined paclitaxel (PTX) with GHSO to design a novel nano-micelles, called GHSO@PTX micelles. Also, we prepared a single targeted nano-micelles (Hyaluronic Acid-Sulcanidone-Ginger Anone) named HSO@PTX. The GHSO@PTX micelles was 159.40±14.30 nm-sized in neutral water. The electron microscopy results showed that the two micelles were relatively uniform in size and spherical in shape. The results of in vitro release experiments shown that GHSO@PTX micelles had better pH sensitivity and ROS responsiveness. Under the conditions of low pH/high H2O2 concentration, the cumulative release of micelles was the largest, which could achieve better therapeutic effects. Cell uptake, cytotoxicity of GHSO@PTX micelles were examined at different concentrations by using SMMC-7721 cells and CAFs. The 3D tumor ball experiment showed that GHSO@Cur micelles were more permeable than HSO@Cur, and proved the superiority of GHSO carrier. It first targeted CAFs cells, opened the physical barrier of tumor cells, and achieved deep penetration of tumor sites. We conducted pathological studies and immunohistochemical studies on isolated tissues and tumor tissue sections of nude mice, and investigated the safety and effectiveness of the preparations H&E staining confirmed its safety, Ki 67 was down-regulated, proving that tumor cell proliferation was inhibited, and the down-regulation of α-SMA and Masson proved that CAFs were inhibited and the preparation GHSO@PTX has the effect of killing CAFs and reducing the fibrosis of the tumor. A promising hyaluronic acid-based nanomedicine platform acts as a new drug delivery system to enhance the deep penetration effect of the tumor, and reduce the degree of fibrosis.

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