Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent

Abstract

A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L = N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are colloidally stable in physiological solution and deliver more P3A1 into breast cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are cytotoxic to several cell models of breast cancer and induce S-phase cell cycle arrest and non-apoptotic cell death in breast cancer cells. By contrast, free P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy and photothermal therapy.

Carbon Nanotubes as an Effective Opportunity for Cancer Diagnosis and Treatment

“…Moreover, they have additional drawbacks, like limited solubility and a poor non-selective biodistribution. To overcome these issue, scientists started to use CNTs as targeted drug delivery [128,129,130,131,132,133]. As already mentioned, CNTs exhibit properties that can be exploited for designing excellent drug nano-vectors.…”

Gold and Carbon-Based Nano-theranostics: An Overview on the Developments and Applications for Cancer Phototherapy

“…However, the A c c e p t e d M a n u s c r i p t combined therapy did not show cancer progression post-treatment. Overall, the investigation suggested that P3A1 + CNT conjugate is beneficial with combining PTT for intractable cancer (53).  Development of Redox system for Cancer: Lin-Hou and co-workers developed a redoxsensitive system of SWCNT for chemo-PTT.…”

“…Add on to this effect, the generated heat altered release of photosensitizer from CNT. 53 The in vivo studies of CNT on mice cancer models (induced with MDA-MB-231 cells) showed that plain P3A1 ablated cancer cells, but could not stop the cancer progression post-treatment. The PTT activated P3A1+CNT, generated mild hyperthermia with cytotoxicity of CNTs.…”

“…Overall, the investigation suggested that P3A1 + CNT conjugate is beneficial with combining PTT for intractable cancer. 53 …”

Large‐Pore Functionalized Mesoporous Silica Nanoparticles as Drug Delivery Vector for a Highly Cytotoxic Hybrid Platinum–Acridine Anticancer Agent

“…An alternative strategy to generate stable dispersions of nanomaterials in high ionic strength media is to introduce PEGylated lipids as surfacec oatings, am ethod we developed to encapsulate and increaset he colloidals tability of anionic nanoparticles including viruses [25] and drug-loaded carbon nanotubes. [26] Brinkera nd co-workers also investigated this technique for encapsulation of MSNs. [9,27] This form of MSN has recentlyshown improved biocompatibility and safety as adelivery vehicle for the prodrug irinotecan compared to liposomal nanoencapsulation alone.…”