Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells

Abstract

Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

Optical imaging of localized chemical events using programmable diamond quantum nanosensors

“…Specifically, complexes of Gd 3+ ions with electronic spin S =7/2 were chemically attached via selectively cleavable linkers to poly[(2-hydroxypropyl)methacrylamide]-based (HPMA) co-polymer chains. Coating of NDs with an HPMA co-polymer shell improves the colloidal stability of the particles, reduces nonspecific interactions with proteins under physiological conditions, maintains the optical properties of NDs and enables further chemical modification3233. The vicinity of Gd 3+ complexes (spin labels) acting as stochastically fluctuating magnetic fields can be sensed by NV relaxometry34353637, providing us a novel route to monitor local changes.…”

“…NDs engineered with our recently developed polymer-coating approach3233 exhibit long-term colloidal stability, reduced nonspecific binding and the capability for convenient chemical modification. In the current study, we connected macrocyclic complexes of Gd 3+ ions with a biocompatible copolymer shell on NDs via selectively cleavable linkers.…”

Novel chemotherapeutics and other therapies for treating high-grade glioma

“…Few other antiangiogenic agents have failed to be promising enough to be tested in Phase III trials. An exception has been cilengitide, an antiangiogenic that targets integrins expressed on tumor endothelial cells, but this was not proven to be effective in Phase III trials [123].…”

“…A Phase II study of the addition of cilengitide with the standard of care (TMZ/RT plus adjuvant TMZ) demonstrated improved PFS6 (69%, 95% CI: 54--80%) and mOS (16.1 months, 95% CI: 13.1 --23.2 months) with the addition of cilengitide compared to historical controls, although after stratification of patients by MGMT methylation status, the effect was only evident in those who possessed the MGMT promoter methylation [124]. A subsequent multicenter, open-label Phase III study (CENTRIC) that included only patients with MGMT promoter methylated GBM, however, did not show an improvement in PFS or OS compared to a control arm that did not receive cilengitide when cilengitide was combined with RT/TMZ followed by adjuvant TMZ for newly diagnosed GBM [123]. Despite failure of efficacy of this particular inhibitor, integrins remain an important potential target for therapy [125].…”

“…cRGD is an example of a surface ligand selective for the a v b 3 integrin receptor that has been explored in this way. Integrins are attractive targets because they are involved in malignant processes, such as proliferation, migration and invasion, and some have been identified as specific to tumors [123]. Cilengitide is a competitive inhibitor of a v b 3 and a v b 5 integrins which promote survival and migration of active endothelial cells during angiogenesis [124].…”