Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Figures

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  Figure 1. The chemical structure of curcumin (a) and doxorubicin (b).

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  Figure 2. Schematic diagram of the proposed mechanism for promoting cellular uptake and overcoming MDR by Cur-pCB (poly(carboxybetaine)) -Dox in MCF-7/Adr cells. The nanosized feature of the zwitterionic antifouling micelles and endocytic pathway to bypass P-gp-mediated drug efflux led to high cellular uptake of the conjugated drugs that were released in the tumor cells of high GSH concentration. However, pCB-Dox and pCB-Cur can be delivered separately into different cells so that the drugs fail to play a synergistic role in inhibiting the MDR effect (a). By contrast, Cur-pCB-Dox codelivers Dox and Cur into the same tumor cells and results in synergistic effects of the two drugs (b). Merging images of cell uptake of pCB-Dox (left), pCB-Dox + pCB-Cur (middle) and Cur-pCB-Dox (right) in MFC-7/Adr cells (c). Cur: curcumin; Dox: doxorubicin; MDR: multidrug resistance; pCB: poly(carboxybetaine). Addapted with permission from [139].

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  Figure 3. Curcumin in promoting antitumor activity of DOX and reversing chemoresistance. ZnCM-SD, curcumin-Zn solid dispersion; EMT, epithelial-to-mesenchymal transition; TGF-β, transforming growth factor-beta; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; DOX, doxorubicin; TIMP-1, tissue inhibitor of matrix metalloproteinase-1; MMP-2, matrix metalloproteinase-2; EGCG, epigallocatechin gallate; AP-1, activator protein-1; NF-κB, nuclear factor-kappaB; P-gp, P-glycoprotein.

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  Figure 4. Curcumin in alleviation of adverse effects of DOX during chemotherapy. DOX, doxorubicin; cyt c, cytochrome C; NF-κB, nuclear factor-kappa B; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-a; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; SOD, superoxide dismutase; GSH, glutathione; CAT, catalase; ROS, reactive oxygen species; PiC, mitochondrial phosphate carrier.

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  Figure 5. (A) Side-by-side comparison of the tumors studied by μCT. Top row: Summation of intensity along the stack of CT slices (n slices ≈400) showing density variations and overall dimensions of the tumors. Bottom row: 3D photorealistic rendering of the tumors. (B) Tumor weight (* p < 0.05 vs. control and blank treatment groups). (C) Representative images of tumors excised at the end point of the study on day 15. Reprinted with permission from [194], ACS Publications, 2019.

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  Figure 6. Curcumin- and DOX-loaded nanovehicles in effective cancer chemotherapy. DOX, doxorubicin; GLUT1, glucose transporter 1; VEGF, vascular endothelial growth factor; P-gp, P-glycoprotein; miRNA, microRNA; MDR, multidrug resistance; TGF-β, transforming growth factor-β.