In vivo enhancement of anticancer therapy using bare or chemotherapeutic drug-bearing nanodiamond particles

Abstract

Background This study investigated the use of nanodiamond particles (NDs) as a promising material for drug delivery in vivo and in vitro. Methods HepG2 cells (a human hepatic carcinoma cell line) were used to determine the characteristics of a nanodiamond-doxorubicin complex (ND-DOX) when taken up by cells in vitro using laser scanning confocal microscopy and dialysis experiments. We also compared the survival rate and histopathology of tumor-bearing mice after treatment with NDs or ND-DOX in vivo. Results In vitro investigation showed that ND-DOX has slow and sustained drug release characteristics compared with free doxorubicin. In vivo, the survival rate of tumor-bearing mice treated with ND-DOX was four times greater than that of mice treated with free doxorubicin. Interestingly, the survival rate in mice treated with NDs alone was close to that of mice treated with free doxorubicin. This indicates that treatment with ND-DOX can prolong the lifespan of tumor-bearing mice significantly compared with conventional doxorubicin and that NDs can have this effect as well. Histopathological analysis showed that neither the NDs nor ND-DOX were toxic to the kidney, liver, or spleen in contrast with the well-known toxic effects of free doxorubicin on the kidney and liver. Further, both the bare NDs and ND-DOX could suppress tumor growth effectively. Conclusion NDs can potentially prolong survival, and ND-DOX may act as a nanodrug with promising chemotherapeutic efficacy and safety.

Nanodiamond-conjugated transferrin as chemotherapeutic drug delivery

“…A conclusion can be drawn that ND-(Tf-DOX) complexes could release active DOX and intercalate DNA to inhibit DNA replication and cell growth. Thus, after the ND-(Tf-DOX) complex entered the cell, DOX molecules were detached from the ND and then migrated into the nucleus, and this would lead to a sustained functional drug release, which was similar to the function of ND-DOX /ND-PEG-DOX complex reported previously by us [3,9,33]. So the ND-(Tf-DOX) nanomedicine has double features for targeted tumor cells and a sustained drug release.…”

“…It has been previously reported that DOX had completely entered the nucleus when free DOX treated cells for only 1 h [33]. So the result indicated that ND-(Tf-DOX) nanoparticles have a slow or sustained drug release profile, which is analogous with ND-DOX [33]. We then addressed the question "What is intracellular localization of ND-(Tf-DOX)?"…”

“…The investigation on the cellular uptake mechanism of ND-(Tf-DOX) will provide important information to the advancement of ND for applications in drug delivery and therapeutics. Here evaluated the mechanism of uptake of the ND-(Tf-DOX) nanomedicine according to the method reported [9,27,33]. The results indicate that the internalization of the ND-(Tf-DOX) mainly goes through a temperature-, energy-, and clathrin-dependent pathway (Fig.…”

Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

“…Some studies indicated that drug molecules can be adsorbed by ND thus forming the complex drug-ND, and with these approaches, water-insoluble drugs may be delivered to cells to effectively exert biological action. The main drugs involved in these studies on drug delivery vehicles, including those for cancer treatment, are doxorubicin hydrochloride (DOX) [22,25], purvalanol A, and 4hydroxytamoxifen [24] as well as insulin therapeutics for diabetes [23].…”

“…It has been suggested that the molecules of chemotherapeutic drugs bond with the ND surface mainly through electrostatic interactions or hydrogen bonds (HBs) between the drug to be studied and a carboxyl or hydroxyl group of functionalized ND [22][23][24][25]. Theoretical studies on chemical properties of the ND-TAM complex are important for understanding the relation between this complex and interaction with an estrogen receptor.…”