A Hybrid Supramolecular Polymeric Nanomedicine for Cascade‐Amplified Synergetic Cancer Therapy

Abstract

Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on β‐cyclodextrin/camptothecin (CPT) host−guest molecular recognition and iron‐carboxylate coordination. Iron ions stabilizing SNPs catalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD‐L1 checkpoint blockade, SNPs enables enhanced immune therapy and a long‐term tumor remission.

Nano-Theranostics Constructed from Terpyridine-Modified Pillar [5]arene-Based Supramolecular Amphiphile and Its Application in Both Cell Imaging and Cancer Therapy

“…The HeLa cells were also selected to investigate the cancer therapy effect of TP5/Zn/PM /Dox in vitro. After incubating with different groups, their viabilities were investigated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays [ 38 , 39 , 40 ]. As shown in Figure 5 a, when the HeLa cells cultivated with TP5/Zn , PM and TP5/Zn/PM (concentration from 0–56 μg mL −1 ), the viabilities of the cells were all above 97%, indicating that our material itself has a good biocompatibility.…”

Supramolecular Dual Polypeptides Induced Tubulin Aggregation for Synergistic Cancer Theranostics

“…No longer content with increasing the water-solubility and biocompatibility of selected substrates, researchers are now vigorously pursuing more reliable methods to regulate the essential living processes by a host–guest interaction. In this context, the combination of macrocycles and biological macromolecules, such as nucleic acids, peptides, and proteins, has been proven as a feasible and powerful means of conferring topologically interesting structures and elaborating functions to a given supramolecular nanosystem. − On one hand, the embedded macrocycles can make direct noncovalent encapsulation with neighboring subunits of biomacromolecules (e.g., amino acid residues), by which the whole conformation and the concomitant biological consequence can be significantly affected. − On the other hand, the inherent cavity of macrocycles can offer numerous confined microenvironments as anchoring points in the three-dimensional (3D) structures of biomacromolecules, by which the exogenous substances can be conveniently captured. , Through leveraging the covalent chemical modification and the noncovalent encapsulation, the coupling of macrocyclic receptors and biomacromolecules has provided bountiful opportunities for fabrication of well-defined topological nanoconstructs. − …”

A supramolecular organometallic drug complex with H2O2self-provision intensifying intracellular autocatalysis for chemodynamic therapy

“…6 However, the packaging strategy of co-delivering CDT agents with the chemotherapeutic drugs inevitably suffered from insufficient drug loading, premature leakage and limited reproducibility, leading to the unsustainable supplementation of H 2 O 2 in cells and inefficient catalytic effects. 1 a ,7 Alternatively, using chemotherapeutic drugs as building blocks to form supramolecular drug self-delivery systems (SDSDSs) has been well investigated. 8 SDSDSs can not only retain the inherent advantages of drug self-delivery systems but also extend the unique virtues of supramolecular interactions, such as dynamic and stimulus responsiveness.…”