Active Nanodiamond Hydrogels for Chemotherapeutic Delivery

Abstract

Nanodiamond materials can serve as highly versatile platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic elements. In this work, doxorubicin hydrochloride (DOX), an apoptosis-inducing drug widely used in chemotherapy, was successfully applied toward the functionalization of nanodiamond materials (NDs, 2-8 nm) and introduced toward murine macrophages as well as human colorectal carcinoma cells with preserved efficacy. The adsorption of DOX onto the NDs and its reversible release were achieved by regulating Cl- ion concentration, and the NDs were found to be able to efficiently ferry the drug inside living cells. Comprehensive bioassays were performed to assess and confirm the innate biocompatibility of the NDs, via real-time quantitative polymerase chain reaction (RT-PCR), and electrophoretic DNA fragmentation as well as MTT analysis confirmed the functional apoptosis-inducing mechanisms driven by the DOX-functionalized NDs. We extended the applicability of the DOX-ND composites toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to assess DOX-ND induced cell death and ND-mediated chemotherapeutic sequestering for potential slow/sustained released capabilities. These and other medically relevant capabilities enabled by the NDs forge its strong potential as a therapeutically significant nanomaterial.

Therapeutic applications of low-toxicity spherical nanocarbon materials

“…115 For example, a nanodiamonddoxorubicin conjugate was found to induce apoptosis in various cancer cell lines and suppress tumor growth in mouse models of liver and mammary cancer. 116,117 By loading this drug on the nanodiamonds, its side effects were diminished and its release was delayed. In one very recent example, a multifunctional platform based on nanodiamonds was constructed, which could be used for selective targeting, imaging and therapy.…”

“…132,133 Through comprehensive bioassays, it was confirmed that nanodiamonds do not induce inflammation or the production of tumor necrosis factor alpha or inducible nitric oxide synthase in cells after incubation. 117 Furthermore, by taking advantage of the intrinsic fluorescence of nanodiamonds, their biodistribution and biocompatibility were evaluated using a C. elegans and a mouse model. It was concluded that nanodiamonds with various surface modifications were nontoxic and highly biocompatible.…”

Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

“…133,134 Despite this consideration, assays that utilize MTT or similar cell vitality stain reagents for measuring cellular proliferation and growth continue to be extensively applied for the routine assessment of true chemotherapeutic cytotoxic anti-neoplastic potency. 7,26,30,[135][136][137][138][139] Fourth, cytotoxic anti-neoplastic potency could have been delineated in vivo against human neoplastic xenographs in animal hosts as a model for human neoplasia where the efficacy of a covalent immunochemotherapeutic frequently tends to be higher than in ex vivo tissue culture based models utilizing the same identical cancer cell type. 39,42,140 The enhanced levels of covalent immunochemotherapeutic potency measured in vivo is presumed in part to be dependent upon contributions from endogenous immune responses that include antibody-dependent cell cytotoxicity (ADCC) phenomenon in concert with complemented-mediated cytolysis initiated by the formation of antigen-immunoglobulin complexes on the exterior surface membrane of ''targeted'' neoplastic cells.…”

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen–nanodiamond hydrogel

“…ND particles, which are capable of mediating improved efficacy and safety by forming complexes around the active agent while preserving its innate functionality (20)(21)(22)(23)(24)(25)(26)(27). ND safety and biocompatibility have been clearly demonstrated in numerous applications ranging from oncology to wound healing (28)(29)(30)(31)(32)(33)(34)(35).…”