Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

Abstract

Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration. Castration-resistant prostate cancer (CRPC) is frequent among patients receiving 18-24 months of androgen deprivation therapy. The nonsteroidal anti-androgen enzalutamide (Enz) used in the treatment of prostate cancer has shown limited bioavailability via oral administration. Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for CRPC intravenous treatment, with high drug loading efficiency. Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study. Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could inhibit the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Further, TP-GQDss exhibited an enhanced cancertargeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC.

Bacterial Genotoxin-Coated Nanoparticles for Radiotherapy Sensitization in Prostate Cancer

“…The utility of combinatorial treatment modalities, specifically radiosensitizers in cancer therapy, was first investigated in the early 1970s [32]. Recently, nanotechnology has paved the way towards the development of an innovative cancer therapy platform [33,34]. Owing to the possibility of modification of nanoparticle composition and surface coating, the functions and specificity of nanoparticles could be more flexibly customized [35][36][37].…”

Advances in Drug Delivery Nanosystems Using Graphene-Based Materials and Carbon Nanotubes

“…The functionalized GQDs were rapidly internalized by castration-resistant prostate cancer cells via endocytosis, and showed good cancer-targeting ability and when loaded with enzalutamide, they inhibited the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Moreover, this GQDs nanocarrier showed a controlled drug release, an enhanced cancertargeting ability and alleviated the side effects of drugs, suggesting that the formulation could be utilized in an intravenous therapy for this type of prostate cancer cell [146]. Nitrogen-Doped GQDs Using a combined density functional theory and molecular dynamic approach, Vatanparast and Shariatinia [147] found that among nitrogen-doped GQDs (N-GQDs), the center N-GQDs exhibit improved performance in gemcitabine (GEM, Figure 4) drug delivery compared to that of pristine GQDs and edge N-GQDs.…”

“…The functionalized GQDs were rapidly internalized by castration-resistant prostate cancer cells via endocytosis, and showed good cancer-targeting ability and when loaded with enzalutamide, they inhibited the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Moreover, this GQDs nanocarrier showed a controlled drug release, an enhanced cancer-targeting ability and alleviated the side effects of drugs, suggesting that the formulation could be utilized in an intravenous therapy for this type of prostate cancer cell [ 146 ].…”

Application of carbon allotropes composites for targeted cancer therapy drugs: A review

“…Moreover, enzalutamide-loaded materials exhibited excellent cancer-targeting and reserved in vitro progression lines of LNCaP and C4-2B cells of prostate cancer. Additionally, nanocarriers of GQDs revealed an enriched ability of cancer-targeting, a measured drug release, and improved drug side impacts, proposing that it could be applied in the therapy of an intravenous related to this prostate tumor cell type [139]. A variety of different carbon allotropes applied in cancer therapy are provided in Table 1.…”