Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP⁺-functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC₅₀ values in the range of 3.12–13.2 µM compared to that of the free BA (9.74–36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

The mitochondria have recently become a novel target in the treatment of cancer. Targeted delivery by nanoparticles (NPs) has shown potential in enhancing existing therapeutic principles. With toxicity remaining a recurring issue, the green synthesis of inorganic NPs and modification with polymers may help to improve stability and biocompatibility. We synthesized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), and functionalized with poly-D-lysine grafted polyethylene glycol (PDL-g-PEG), and the mitochondrial targeting triphenylphosphonium cation, and thereafter assessed their mitochondrial delivery capacity of paclitaxel in cancer cells in vitro. This PDL-g-PEG coated EGCG-AuNPs were further assessed for their laminin receptor avidity and mitochondrial localisation potential, upon functionalisation with the delocalised cation, triphenylphosphine. The laminin receptor dependent uptake and mitochondrial localisation of targeted T-Au(PDL-g-PEG) NPs were confirmed by ICP-OES and fluorescent microscopy. Their delivery of paclitaxel to the mitochondria of cancer cells elicited significant cytotoxicity especially in the human cervical carcinoma (HeLa) cell line, compared to the untargeted T-Au(PDL-g-PEG) and free drugs. Mechanistic studies implicated caspase dependent apoptosis as the mechanism of cell death. Our findings demonstrate the capacity of T-Au-[PDL-PEG] NPs to preferentially localize in the tumour mitochondria, and confirms the potential impact of subcellular targeting, especially to the mitochondria in cancer cells for an improvement in the therapeutic indices of these drugs.

Drought and heat stress is known to influence the accumulation of mineral content, antioxidant activity, phenolics, flavonoids and other bioactive compounds in many tolerant leafy vegetables. Amaranthus plants can tolerate adverse weather conditions, especially drought and heat. Therefore, evaluating the influence of drought and heat stress on commercially and medically important crop species like Amaranthus is important to grow the crop for optimal nutritional and medicinal properties. This study investigated the influence of drought and heat stress and a combination of both on the accumulation of phenolic and flavonoid compounds and the antioxidant capacity of African Amaranthus caudatus, A. hypochondriacus, A. cruentus and A. spinosus. Phenolic and flavonoid compounds were extracted with methanol and aqueous solvents and were quantified using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Caffeic acid was the main phenolic compound identified in aqueous extracts of A. caudatus and A. hypochondriacus. Rutin was the most abundant flavonoid compound in all the Amaranthus species tested, with the highest concentration found in A. caudatus. The results suggest a strong positive, but species and compound-specific effect of drought and heat stress on bioactive compounds accumulation. We concluded that heat stress at 40 °C under well-watered conditions and combined drought and heat stress (at 30 °C and 35 °C) appeared to induce the accumulation of caffeic acid and rutin. Hence, cultivation of these species in semi-arid and arid areas is feasible.

The last few decades have seen an overwhelming increase in the amount of research carried out on the use of inorganic nanoparticles. More fascinating is the tremendous progress made in the use of chalcogen and chalcogenide nanoparticles in cancer theranostics. These nanomaterials, which were initially synthesized through chemical methods, have now been efficiently produced using different plant materials. The paradigm shift towards the biogenic route of nanoparticle synthesis stems from its superior advantages of biosafety, eco-friendliness, and simplicity, among others. Despite a large number of reviews available on inorganic nanoparticle synthesis through green chemistry, there is currently a dearth of information on the green synthesis of chalcogens and chalcogenides for cancer research. Nanoformulations involving chalcogens such as sulfur, selenium, and tellurium and their respective chalcogenides have recently emerged as promising tools in cancer therapeutics and diagnosis. Similar to other inorganic nanoparticles, chalcogens and chalcogenides have been synthesized using plant extracts and their purified biomolecules. In this review, we provide an up-to-date discussion of the recent progress that has been made in the plant-mediated synthesis of chalcogens and chalcogenides with a special focus on their application in cancer theranostics.