Ultrasound-Triggered Spatiotemporal Delivery of Topotecan and Curcumin as Combination Therapy for Cancer

Abstract

Chemotherapy is limited by the low availability of drug at the tumor site and drug resistance by the tumor. In this report we describe a combination therapy for codelivery of two anticancer drugs with spatiotemporal control by ultrasound pulses. We developed curcumin and topotecan-coencapsulated nanoconjugates Cur_Tpt_NC.MB to have an ultrasound contrast property. MDA MB 231 and B16F10 cells were incubated with Cur_Tpt_NC.MB and exposed to ultrasound. Ultrasound exposure reduced the IC 50 concentration of topotecan and curcumin significantly (P , 0.05) compared with free drug.Antitumor efficacy study of the Cur_Tpt_NC.MB in B16F10 melanoma tumor-bearing C57BL/6 mice showed that ultrasound exposure of right tumor reduced growth by 3.5 times compared with the unexposed left tumor of same mice and 14.8 times compared with a group treated with a physical mixture of drugs. These results suggest that the nanotherapeutic system we developed induces site-specific inhibition of tumor growth at a high rate and has the potential to be used as a therapeutic regimen for spatiotemporal delivery of dual drugs for treatment of cancer.

Spatiotemporal molecular imaging is a critical part of spatiotemporal molecular medicine

“…Ultrasound-oriented spatiotemporal delivery of drugs could increase the cell sensitivity to drugs and the specificity of drug-acted locations. 11 Clinical images enter an era of spatiotemporal multimodal organ function and construction at various layers, orientations, and aspects. For example, the integration of four-dimensional NMR with ultrasound images, spatial cardiac electrography, and organ-wide histological architecture or gene expression will create a new atlas with cardiac motions, electric signals, cell distributions, transcriptional networks, and signal pathways for clinicians to refer to clinical phenomes of patients to make precise decisions.…”

“…Four‐dimensional ultrasound images could spatiotemporally define and characterize the qualification and visualization of protein deposition, mineral distribution, cell positioning, tissue property, and microenvironmental events, highly dependent upon ultrasound transducers, probes, and programs. Ultrasound‐oriented spatiotemporal delivery of drugs could increase the cell sensitivity to drugs and the specificity of drug‐acted locations 11 . Clinical images enter an era of spatiotemporal multimodal organ function and construction at various layers, orientations, and aspects.…”

Nanotechnology approaches in the current therapy of skin cancer

“…reported antiproliferative and antimetastatic effects in vitro and in vivo in a murine model of melanoma treated with docetaxel and chlorin e6 (Ce6)-loaded NPs and the application of lowintensity ultrasound (1 W/cm2) [318]. Prasad and Banerjee (2019) were the first to report the development of nanoconjugate and microbubble (MB) nanocapsules that were associated with ultrasound-mediated co-delivery of hydrophobic and hydrophilic drugs (curcumin and topotecan). The results showed that exposure to ultrasound (2 W/cm 2 ) was significant in reducing the toxicity induced by free drug concentrations of curcumin and topotecan in vitro that was accompanied by an increase in necrotic and apoptotic cells.…”

“…These results suggest that the ultrasound application facilitated tumor permeabilization and that insonation catalyzed release on demand and thus facilitated simultaneous release and internalization. Additional factors may have played a role in tumor reduction, such as energy production by cavitation, ROS formation, and localized mild hyperthermia that led to noncoagulative necrosis [319].…”

Microbubble based sonoporation — from the basics into clinical implications

“…Chandrashekhar Prasad and Rinti Banerjee developed curcumin and topotecan co-encapsulated nanoconjugates Cur_Tpt_NC with ultrasound contrast property. They co-delivered mentioned drugs with spatiotemporal control by ultrasound pulses to melanoma tumor on mice model reaching 3.5 times reduction of tumour growth in comparison to unexposed mice and 14.8 time reduction in comparison to the group treated with physical mixture of this drugs [43].…”