Chemotherapeutic agents are considered one of the strategies in treating cancer. However, their use is faced by many challenges, such as poor water solubility leading to poor bioavailability and non-selective targeting of cancerous cells leading to diminished therapeutic actions and systemic adverse effects. Many approaches were adopted to overcome these drawbacks and to achieve the targeted delivery of the chemotherapeutic agents to the cancerous cells while minimizing adverse effects. Recently, supramolecular systems such as macrocycles have gained attention in the field of cancer therapy for being able to encapsulate different anticancer drugs via either host-guest complexation or self-assembly leading to a myriad of advantages. This review highlights the most recent studies concerned with the design of such novel systems for cancer therapy.

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P-sulfonatocalix[n]arenes have demonstrated a great potential for encapsulation of therapeutic drugs via host-guest complexation to improve solubility, stability, and bioavailability of encapsulated drugs. In this work, guest-host complexes of a third-generation anticancer drug (oxaliplatin) and p-4-sulfocalix[n]arenes (n = 4 and 6; p-SC4 and p-SC6, respectively) were prepared and investigated, using 1H NMR, UV, Job’s plot analysis, and DFT calculations, for use as cancer therapeutics. The peak amplitude of the prepared host-guest complexes was linearly proportional to the concentration of oxaliplatin in the range of 1.0 × 10−5 M−1 to 2.1 × 10−4 M−1. The reaction stoichiometry between either p-SC4 or p-SC6 and oxaliplatin in the formed complexes was 1:1. The stability constants for the complexes were 5.07 × 104 M−1 and 6.3 × 104 M−1. These correspond to complexation free energy of −6.39 and −6.52 kcal/mol for p-SC4 and p-SC6, respectively. Complexation between oxaliplatin and p-SC4 or p-SC6 was found to involve hydrogen bonds. Both complexes exhibited enhanced biological and high cytotoxic activities against HT-29 colorectal cells and MCF-7 breast adenocarcinoma compared to free oxaliplatin, which warrants further investigation for cancer therapy.

Amphiphilic macrocycles, such as p -sulfonatocalix[6]arenes ( p -SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L . seeds. Ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p -SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of −30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC 50 values of HARF encapsulated in p -SC6 (H/ p -SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC 50 of the H/ p -SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p -SC6 significantly increases its antioxidant and cytotoxic activities.

Supramolecular systems (macromolecules), such as calix­[n]­arenes (SCn), cyclodextrins (CDs), and cucurbiturils (CBs), are promising vehicles for anticancer drugs. In this work, guest–host complexes of carboplatin, a second-generation platinum-based anticancer drug, and p-4-sulfocalix­[n]­arenes (n = 4 and 6; PS4 and PS6, respectively) were prepared and studied using 1H NMR, UV, Job’s plot analysis, HPLC, and density-functional theory calculations. The experimental and the computational studies suggest the formation of 1:1 complexes between carboplatin and each of PS4 and PS6. The stability constants of the formed complexes were estimated to be 5.3 × 104 M–1 and 9.8 × 104 M–1, which correspond to free energy of complexation of −6.40 and −6.81 kcal mol–1, in the case of PS4 and PS6, respectively. The interaction free energy depends on the different inclusion modes of carboplatin in the host cavities. UV–vis findings and atoms in molecules analysis showed that hydrogen bond interactions stabilize the host–guest complexes without the full inclusion in the host cavity. The in vitro anticancer study revealed that both complexes exhibited stronger anticancer activities against breast adenocarcinoma cells (MCF-7) and lung cancer cells (A-549) compared to free carboplatin, preluding to their potential use in cancer therapy.

This study reports a facile and eco-friendly method for the green synthesis of platinum and palladium nanoparticles (Pt NPs and Pd NPs) using Peganum harmala seed alkaloid fraction. The ζ-potential of the synthesized Pt NPs, Pd NPs and Pt–Pd NPs were −11.2 ± 0.5, −9.7 ±1.2, and −12.7 ± 2.1 mV; respectively. Transmission electron microscopy (TEM) revealed the formation of spherical-shaped nanoparticles with smooth margins. The mean diameters of the synthesized Pt NPs, Pd NPs, and Pt–Pd NPs were determined using TEM analysis and were found to be 20.3 ± 1.9, 22.5 ± 5.7, and 33.5 ± 5.4 nm, respectively. The nanoparticles’ bioreduction was confirmed by ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, and their organic contents were determined by thermal gravimetric analysis (TGA). The Pt–Pd NPs mixture showed more pronounced antioxidant activity of 843.0 ± 60 μM Trolox equivalent (TE)/mg NPs compared to the individual Pt NPs (277.3 ± 13.5 μM TE/mg NPs) and Pd NPs (167.6 ± 4.8 μM TE/mg NPs). Furthermore, the Pt–Pd NPs exhibited significant cytotoxic activities against lung cancer (A549) and breast adenocarcinoma (MCF-7) cells, IC50 of 8.8 and 3.6 µg/mL, respectively; as compared to Pt NPs (IC50 of 10.9 and 6.7 µg/mL, respectively) and Pd NPs (IC50 of 31 and 10.8 µg/mL, respectively and compared to carboplatin (IC50 of 23 and 9.5 µg/mL, respectively). Moreover, molecular docking studies were conducted to explore the possible anticancer and antioxidant mechanisms of the biogenic nanoparticles. Pt NPs, Pd NPs, and their mixture showed inhibitory activity against cysteine proteinase, which supports their high antitumor activity, but moderate antioxidant activity. In conclusion, Pd-Pt NPs mixture prepared using harmala seed alkaloid fraction showed potential as effective antineoplastic agents.

Palladium nanoparticles (Pd NPs) showed great potential in biomedical applications because of their unique physicochemical properties. Various conventional physical and chemical methods have been used for the synthesis of Pd NPs. However, these methods include the use of hazardous reagents and reaction conditions, which may be toxic to health and to the environment. Thus, eco-friendly, rapid, and economic approaches for the synthesis of Pd NPs have been developed. Bacteria, fungi, yeast, seaweeds, plants, and plant extracts were used to prepare Pd NPs. This review highlights the most recent studies for the biosynthesis of Pd NPs, factors controlling their synthesis, and their potential biomedical applications.

Cancer chemotherapeutics face several challenges, including uncontrollable drug release, off-target toxic effects, and poor bioavailability. Recently, supramolecular nanovesicles, such as calix[n]arenes (CXs), cyclodextrins (CDs), cucurbiturils (CBs), and pillar[n]arenes (PRs), have attracted attention as potential smart nanocarriers for chemotherapeutics because of their exceptional cavities that can achieve high encapsulation capacity and accommodate both hydrophilic and hydrophobic drugs. In addition, they can be functionalized with different stimuli-responsive groups, which facilitate controlled drug release. Supramolecular nanovesicles, loaded with drugs and decorated with stimuli-responsive targeting moieties, are designed by either host−guest complexation or self-assembly of amphiphilic cavitands. Pillar[n]arenes, in particular, are novel supramolecular host molecules that have recently been employed in cancer targeted drug delivery because of their symmetric pillar-shaped structure, simplicity of functionalization, and biocompatibility. This review summarizes state-of-the-art strategies for developing single or multiple stimuli-responsive pillar[n]arene nanovesicles for effective cancer treatment. TARGETED DELIVERY OF CHEMOTHERAPEUTICS USING SUPRAMOLECULAR APPROACHES