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. 2018 Apr 24;8:114.
doi: 10.3389/fonc.2018.00114. eCollection 2018.

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

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Free PMC article

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Sayeda Yasmin-Karim et al. Front Oncol. .
Free PMC article

Abstract

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

Keywords: biomaterials; cancer; cannabinoids or endocannabinoids; radiotherapy; survival.

Figures

Figure 1
Figure 1
Small animal radiation research platform (SARRP). Showing pictures of set-up for (A) image-guided radiotherapy (RT) with computed tomography imaging done using 65 kVp photons at 0.5 mA, (B) in vitro studies with RT delivered using 220 kVp photons and 13 mA.
Figure 2
Figure 2
In vitro antitumor effect of cannabinoid (CBD). (A) Clonogenic assay results comparing results for different CBD radiotherapy (RT) dose combinations. (B) Perspective results of synergistic outcomes when combining RT at 4 Gy with different CBD doses.
Figure 3
Figure 3
Sustained release of cannabinoid (CBD). (A) One design of multifunctional smart biomaterial (SRB) made of Food and Drug Administration-approved biocompatible biodegradable polymer loaded with a payload of CBDs/nanoparticles (NPs); (B) actual SRBs with payload; (C,D) in vitro release of CBD payload from SRB, demonstrating the ability for (C) sustained release over many days, and (D) quick release. The release kinetics (i.e., how slow or fast) can be optimized to treatment schedules, by varying the degree of cross-linking in the polymer or the polymer weighting. (E) Computed tomography image of mouse imaged over time with small animal radiation research platform showing degradation of SRB as payload is released over time in the tumor on the right side of image. (F) Average pixel intensity from maximum amplitude image for all image slices. The data are obtained from evaluating the same region of interest in the processed maximum intensity images.
Figure 4
Figure 4
Antitumor effect of cannabinoid (CBD) and smart biomaterial (SRB)-CBD in vivo. (A) Lung tumor volume measurements highlight greater inhibition of tumor growth when using CBD-loaded SRBs compared to direct intratumoral administration (IT injection) and control cohorts: empty SRB. (B) Inhibition of lung tumor growth when using SRBs for sustained delivery of CBD, confirming higher killing effect of sustain release of CBD in the tumors. The Kaplan–Meier survival curve showing survival time (in days) for mice tumors treated with an empty SRB (n = 11), direct CBD (n = 13), CBD-loaded SRB (n = 12), and control cohort (n = 12). (C,D) A pilot study showing increased survival benefit of pancreatic tumor treated with (C) direct IT injection of CBD compared to control and (D) using SRBs for sustained delivery of CBD.
Figure 5
Figure 5
Illustration of innovative approach with potential to significantly enhance therapeutic efficacy using cannabinoids (CBDs). (A) Currently used commercially available inert radiotherapy (RT) biomaterials, e.g., fiducials (CIVCO Medical); (B) one design of multifunctional biomaterial [smart biomaterial (SRB)] made of Food and Drug Administration-approved biocompatible biodegradable polymer loaded with a payload of CBDs; (C) potential clinical translation pathway is envisioned where the smart SRB could simply replace the inert biomaterials currently used for image-guided RT. Such replacement would come at no additional inconvenience to cancer patients. Once in place the SRB can be activated to sustainably release its payload as the polymer coating degrades for greater effective tumor cell kill working in synergy with RT as highlighted by our study results.

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