β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells

Abstract

Despite the widespread clinical application of chemotherapeutic anticancer drugs, their adverse side effects and inefficient performances remain ongoing issues. A drug delivery system (DDS) designed for a specific cancer may therefore overcome the drawbacks of single chemotherapeutic drugs and provide precise and synergistical cancer treatment by introducing exclusive stimulus responsiveness and combined chemotherapy properties. Herein, we report the design and synthesis of a supramolecular drug delivery assembly 1 constructed by orthogonal self-assembly technique in aqueous media specifically for application in liver cancer therapy. Complex 1 incorporates the β-cyclodextrin host molecule-functionalized organoplatinum(II) metallacycle 2 with two specific stimulus-responsive motifs to the signaling molecule nitric oxide (NO), in addition to the three-armed polyethylene glycol (PEG) functionalized ferrocene 3 with redox responsiveness. With this molecular design, the particularly low critical aggregation concentration (CAC) of assembly 1 allowed encapsulation of the commercial anticancer drug doxorubicin (DOX). Controlled drug release was also achieved by morphological transfer via a sensitive response to the endogenous redox and NO stimuli, which are specifically related to the microenvironment of liver tumor cells. Upon combination of these properties with the anticancer ability from the platinum acceptor, in vitro studies demonstrated that DOX-loaded 1 is able to codeliver anticancer drugs and exhibit therapeutic effectiveness to liver tumor sites via a synergistic effect, thereby revealing a potential DDS platform for precise liver cancer therapeutics.

Hierarchical Hydrogels with Ordered Micro-Nano Structures for Cancer-on-a-Chip Construction

“…The quantitative results indicated that with the increase of DOX or CPT concentration, the cell viability continued to decrease. In addition, with the addition of CPT, the cell viability of the CPT-DOX group was lower than that of the DOX group and the CPT group under the synergistic action of drugs, which was consistent with related reports [ 38 , 39 ]. The above results proved the effectiveness of the liver cancer-on-a-chip constructed by integrating the hierarchical hydrogel with ordered micro-nano structure and microfluidic chip in drug screening.…”

Anthracene-induced formation of highly twisted metallacycle and its crystal structure and tunable assembly behaviors

“…Among these, coordination-driven self-assembly (CDSA) provides a powerful strategy for producing metal organic complexes (MOCs) with various sizes, shapes, and metal/ligand stoichiometries (20)(21)(22)(23)(24)(25)(26). To date, diverse MOCs have been developed by coordination between metal ions and organic ligands, and these exhibit superiority over their precursors and can be used in emission units, sensors, and hosts as well as in applications in biomedical diagnosis and catalysis (27)(28)(29)(30)(31)(32)(33)(34). Platinum-based architectures are the most extensively studied of these structures and have undergone the most rapid development, due to their facile synthesis (35)(36)(37)(38)(39).…”

Visualizing molecular weights differences in supramolecular polymers

“…Given the reversible noncovalent bonds embodied in supramolecular polymers, they typically exhibit not only polymer-like properties as bulk materials and in solution, but also dynamic characteristics. These latter attributes often have no parallel in the case of covalent polymers and include inter alia reversible formation, recyclability, and stimulus responsiveness ( 8 – 26 ), including to anions whose role in the fields of biology, chemistry, energy, and supramolecular chemistry is well appreciated ( 27 – 42 ). These key features complicate molecular weight determinations, as does the fact that a distribution of molecular weights around an average is generally observed.…”

“…These key features complicate molecular weight determinations, as does the fact that a distribution of molecular weights around an average is generally observed. Moreover, due to the dynamic nature of noncovalent bonds, the monomers used to create supramolecular polymers can assemble in a variety of aggregation modes ( 7 , 39 ). For instance, when the monomer concentration is low, cyclic species or oligomers are more likely to form.…”

“…As such, the molecular weights of supramolecular polymers have to be inferred from less-direct measurements ( 43 – 45 ). For example, the average degree of supramolecular polymerization can be calculated (DP cal ) by measuring the equilibrium constant of the interaction between monomers and applying various theoretical models ( 39 , 46 , 47 ). Alternatively, in certain cases the molecular weights of supramolecular polymers can be deduced empirically from the intrinsic viscosities using the Mark–Houwink equation ( 48 , 49 ).…”