Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use

Abstract

In the current chapter, a new strategic compilation of phytochemicals with potent antitumor properties has been addressed, most importantly focusing on cell cycle arrest and apoptotic signaling mechanism. A promising approach in tumor prevention is to eliminate cancer cells preferably via cell cycle arrest and programmed cell death with lesser harm to neighboring normal cells. Cancer cells have a survival advantage to escape apoptosis and relentlessly divide to proliferate, gearing up the cell cycle process. Recently, the use of phytochemical-derived conjugated chemotherapeutic agents has increased dramatically owing to its biocompatibility, low cytotoxicity, low resistance, and dynamic physiochemical properties discriminating normal cells in the treatment of various cancer types. For decades, biomedical investigations have targeted cell cycle and apoptotic cell death mechanism as an effective cancer-killing tool for systemically assessing the potential biological interactions of functional phytocompounds compared to its synthetic counterparts during their complete life cycles from entry, biodistribution, cellular/molecular interactions to excretion. Newly emerging nanotechnology application in anticancer drug formulations has revolutionized cancer therapy. Tissue-specific phyto-nanomedicine plays a vital role in advanced cancer diagnostics using liposome, micelle, and nanoparticles as a precise and effective delivery vehicle. This chapter specifically focuses on the therapeutic phytomolecules approved by the Food and Drug Administration (FDA, USA) along with phyto-chemopreventives currently on clinical trials (Phase-I/II/III/IV). Besides, detailed coverage is given to the FDA-approved nanotechnology-based formulations only in the areas of cancer theranostics via cell cycle arrest and apoptotic pathways including present challenges and future perspectives.

Keywords: apoptosis; cancer therapeutics; cell cycle arrest; chemo-preventive agents; clinical trials; phytochemicals.

Figure 1

Percentage of global cancer deaths according to cancer types. Estimated percentages of cancer deaths include both sexes and all age groups in 2018 Notes:Data source: WHO, GLOBOCAN, 2018.2

Figure 2

Phytochemicals inducing cancer cell growth arrest and cell death through cell cycle signaling checkpoint modulation. Phytochemicals induce cell cycle arrest at G0/G1 (resting phase, metabolically active), G1/S (active growth phase), S/G2 (chromosome replication and cell division), G2/M (DNA damage phase) and M (metaphase-mitotic spindle) checkpoints followed by irreparable DNA damage, seizing the cell from further growing, thus compelling cancer cells to undergo apoptosis process.

Figure 3

Anticancer phytochemicals inducing DNA damage and cell cycle growth seizure progressing apoptosis for tumor clearance.

Figure 4

Intrinsic and extrinsic apoptotic cancer cell death mechanism with the treatment of phyto-nanocomposite inducing DNA damage and cell cycle arrest. Phytochemicals in combination with nanoparticles and anticancer drugs produce excessive ROS inducing oxidative stress that results in cancer cell death triggering various signaling pathways via mitochondrial and receptor-mediated apoptosis.

Figure 5

Comparative Ga-68 PSMA PET CT scans before and after the administration of Doceaqualip. Notes: Left panel: Images obtained in November, 2015, showing post-TURP changes, small mild nodular hypermetabolism in the left posterior peripheral zone (likely representing residual prostatic disease) and extensive FDG-avid heterologous osteosclerotic lesions. Right panel: Images obtained in January, 2016, showing post-TURP changes, mild interval regression of the nodular hypermetabolism in the left posterior peripheral zone and morphologically stable heterogenous osteosclerotic lesions with internal regression of the metabolic activity. PSMA, prostate-specific membrane antigen; PET, positron emission tomography; CT, computed tomography; TURP, transurethral resection of the prostate; FDG, fluorodeoxyglucose. Adapted with permission from Atrafi F, Eerden R, van Hylckama Vlieg Met al Intratumoral Comparison of Nanoparticle Entrapped Docetaxel (CPC634) with Conventional Docetaxel in Patients with Solid Tumors. Clinical Cancer Research. 2020;26:clincanres.0008.2020. ©copy right (2020), Molecular and Clinical Oncology.