Following cytotoxic nanoconjugates from injection to halting the cell cycle machinery and its therapeutic implications in oral cancer

Abstract

Background The concept of personalized therapy has been proven to be a promising approach. A popular technique is to utilize gold nanoparticles (AuNPs) as drug delivery vectors for cytotoxic drugs and small molecule inhibitors to target and eradicate oral cancer cells in vitro and in vivo. Both drug and nanocarrier designs play important roles in the treatment efficacy. In our study, we standardized the nanosystem regarding NPs type, size, surface ligands and coverage percentage leaving only the drugs mode of action as the confounding variable. We propose that similarly constructed nanoparticles (NPs) can selectively leverage different conjugated drugs irrelevant to their original mode of action. If proven, AuNPs may have a secondary role beyond bypassing cancer cell membrane and delivering their loaded drugs. Methods We conjugated 5- fluorouracil (5Fu), camptothecin (CPT), and a fibroblast growth factor receptor1-inhibitor (FGFR1i) to gold nanospheres (AuNSs). We followed their trajectories in Syrian hamsters with chemically induced buccal carcinomas. Results Flow cytometry and cell cycle data shows that 5Fu- and CPT- induced a similar ratio of S-phase cell cycle arrest as nanoconjugates and in their free forms. On the other hand, FGFR1i-AuNSs induced significant sub-G1 cell population compared with its free form. Despite cell cycle dynamics variability, there was no significant difference in tumor cells’ proliferation rate between CPT-, 5Fu- and FGFR1i- AuNSs treated groups. In our in vivo model, FGFR1i-AuNSs induced the highest tumor reduction rates followed by 5Fu- AuNSs. CPT-AuNSs induced significantly lower tumor reduction rates compared with the 5Fu- and FGFR1i- AuNSs despite showing similar proliferative rates in tumor cells. Conclusions Our data indicates that the cellular biological events do not predict the outcome seen in our in vivo model. Furthermore, our results suggest that AuNSs selectively enhance the therapeutic effect of small molecule inhibitors such as FGFR1i than potent anticancer drugs. Future studies are required to better understand the underlying mechanism.

Nanochemistry of gold: from surface engineering to dental healthcare applications

“…203,204 Hamid et al conjugated 5-FU, camptothecin, and a fibroblast growth factor receptor1-inhibitor (FGFR1i) to GNSs and studied their effects on an animal buccal carcinomas model. 93 They found FGFR1i-GNSs induced the highest tumor reduction rates followed by 5-FU-GNSs. The platelet-facilitated photothermal tumor therapy (PLT-PTT) strategy could also be used to treat HNSCC.…”

“…91 Functionalized GNSs have been proved in various in vitro studies, such as in the regeneration and antibacterial treatment of periodontal tissue and teeth, the osseointegration of dental implants and the resection of head and neck carcinomas. 10,15,41,92,93 For example, ampicillin-functionalized GNSs proved to be an effective broad-spectrum fungicide, capable of resisting both Gram-negative and Gram-positive bacteria. 94 For GNSs to maintain a stable dispersion in water or saline buffers when utilized in living systems, they necessitate a biocompatible and hydrophilic surface.…”

Nanoparticles as drug delivery systems in the treatment of oral squamous cell carcinoma: current status and recent progression

“…Gold NPs, as DDS, have been extensively studied, and promising results were observed. For example, Abdel Hamid et al (2021) used AuNS as a drug delivery vectors to evaluate the combination effect of cytotoxic chemo-drugs 5- fluorouracil (5-Fu), camptothecin (CPT), and small molecule inhibitor fibroblast growth factor receptor1-inhibitor (FGFR1i) both in vitro and in vivo in the oral cancer, survival analysis data showed that Syrian golden male hamsters treated with conjugating AuNSs with FGFR1i, 5Fu, and CPT could remarkedly enhance survival time to more than 27 days, which was much longer than animals treated with free FGFR1i (survival time 13.5 days). In addition, animals treated with FGFR1i-AuNSs induced the highest tumor volume reduction with a 2-fold decrease (−63.09%) compared with those injected by CPT-AuNSs (−32.1%) or 5Fu-AuNSs (−43.4%) ( Abdel Hamid et al, 2021 ).…”

“…For example, Abdel Hamid et al (2021) used AuNS as a drug delivery vectors to evaluate the combination effect of cytotoxic chemo-drugs 5- fluorouracil (5-Fu), camptothecin (CPT), and small molecule inhibitor fibroblast growth factor receptor1-inhibitor (FGFR1i) both in vitro and in vivo in the oral cancer, survival analysis data showed that Syrian golden male hamsters treated with conjugating AuNSs with FGFR1i, 5Fu, and CPT could remarkedly enhance survival time to more than 27 days, which was much longer than animals treated with free FGFR1i (survival time 13.5 days). In addition, animals treated with FGFR1i-AuNSs induced the highest tumor volume reduction with a 2-fold decrease (−63.09%) compared with those injected by CPT-AuNSs (−32.1%) or 5Fu-AuNSs (−43.4%) ( Abdel Hamid et al, 2021 ). When Gamal-Eldeen et al (2021) examined the effect of gum arabic encapsulated gold NPsNPs (GA-AuNPs) on the hypoxia regulators in tongue squamous cell carcinoma (CAL-27 cells) in vitro , they found that GA-AuNPs can remarkably reduce cell viability with IC50 of 392.3 and 247.3 μg/mL after 24 and 48 h, respectively, and increase CAL-27 cell death rate via enhanced apoptosis.…”

Mastoparan, a Peptide Toxin from Wasp Venom Conjugated Fluvastatin Nanocomplex for Suppression of Lung Cancer Cell Growth

“…NCs for cancer chemotherapy have emerged out to be promising and conducive for personalized medicine [ 12 ]. Interestingly, drug–polymer, drug–lipid, and drug–DNA NCs are reported for cancer chemotherapy [ 13 , 14 , 15 , 16 ].…”