Supramolecular Drug Delivery Systems

Supramolecular drug delivery systems harness the principles of non-covalent assembly to transport therapeutic agents with enhanced specificity and controlled release. By employing molecular hosts such as cyclodextrins, calixarenes and cucurbiturils, researchers can encapsulate hydrophobic or sensitive payloads within nanoscale carriers, improving solubility, stability and bioavailability. Amphiphilic block copolymers, functionalised polymers and hydrogels further exploit host–guest inclusion, hydrogen bonding, π–π stacking and coordination interactions to form stimuli-responsive platforms that release cargo in response to pH, temperature or redox conditions. These systems can be engineered for passive targeting via the enhanced permeability and retention effect, or for active targeting through conjugation to ligands such as peptides, antibodies or aptamers. Applications encompass oncology, infectious disease and gene therapy, where controlled spatio-temporal release reduces systemic toxicity and enhances therapeutic index. Despite significant progress, challenges remain in large-scale manufacturing, in vivo stability and immunocompatibility. Ongoing efforts focus on modular design, green synthesis and clinical translation of supramolecular carriers that offer programmable function, multivalent interactions and real-time imaging capabilities for personalised medicine.

Research from Nature Portfolio

Recent advances have demonstrated the assembly of paclitaxel prodrugs and porphyrin moieties within permethyl-β-cyclodextrin grafted hyaluronic acid to form biodegradable, fluorescent nanoparticles that target tumour cells via receptor-mediated endocytosis, achieving high drug loading with reduced off-target toxicity. Further, amphiphilic β-cyclodextrin–polymer conjugates have been engineered into pH-responsive micelles co-delivering doxorubicin alongside a natural adjuvant, enabling synergistic apoptosis induction in breast cancer cells through precise control over release kinetics and activation of intrinsic cell-death pathways.

Supramolecular Drug Delivery Systems publication trend

The graph below shows the total number of articles in supramolecular drug delivery systems across all publications each year (not limited to Nature Index journals).

Technical terms

Supramolecular chemistry: Design and study of complexes formed through non-covalent interactions such as hydrogen bonding and host–guest inclusion.

Host–guest interaction: Specific non-covalent binding between a host molecule’s cavity and a complementary guest molecule.

Cyclodextrin: Cyclic oligosaccharide host with a hydrophobic interior and hydrophilic exterior, used to encapsulate guest drugs.

Micelle: Self-assembled aggregate of amphiphilic molecules forming a core–shell structure for drug encapsulation.

Exosome: Nanoscale extracellular vesicle released by cells, utilised as natural carriers for biomolecular delivery.

References

1. Supramolecular nanomedicines based on host–guest interactions of cyclodextrins. Exploration (2023).
2. Supramolecular Nano‐Grid Platform to Load and Deliver Liposomes and Exosomes. Small Structures (2024).
3. Thermo/pH dual-responsive micelles based on the host–guest interaction between benzimidazole-terminated graft copolymer and β-cyclodextrin-functionalized star block copolymer for smart drug delivery. Journal of Nanobiotechnology (2022).
4. Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells. Scientific Reports (2021).