Synthesis of nanodiamond–daunorubicin conjugates to overcome multidrug chemoresistance in leukemia

Abstract

Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains.

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

“…[5][6][7] In particular, the successful use of DNDs in cancer treatment has greatly captured the attention of the scientific community. [8][9][10][11] Although numerous plant compounds have been widely studied for their antitumor activities, [12][13][14][15] to date only three papers describe the coupling of natural secondary metabolites with DNDs aimed at enhancing their bioavailability and bioactivity. The first of them illustrated the antimicrobial activity of menthol ((1R,2S,5R)-2-isopropyl-5-methylcyclohexanol)-modified ND particles.…”

USNCTAM perspectives on mechanics in medicine

“…Although researchers now have a greatly expanded set of knobs to turn when designing NPs, it is generally not clear how a change to a specific vehicle feature will alter the effectiveness of a drug, and hence design of novel drug carriers requires extensive and costly parametric studies that are generally specific to the system upon which the experiments were performed. Theoretical and computational modelling of the delivery process can greatly reduce the need for physical experiments and provide general design principles to expedite the design process [4][5][6][7][8][9].…”

What’s up in nanomedicine?

“…Nanodiamonds (NDs) is a class of nano particles that has already shown both the delivery and the enhanced function of its payload (17). Man and coworkers investigated a novel therapeutic payload (18). NDs were developed such that daunorubicin (DNR) could be reversibly bound and released.…”

“…With this, they demonstrated the potential to improve cancer treatment in particular regarding resistant strains. Man and coworkers (18) suggested that with the introduction of a gene therapy component, the expression of the proteins causing MDR might be actively reduced. NDs have already been investigated and showed excellent biocompatibility in vitro.…”