Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

Area of Science:

• Supramolecular Chemistry
• Nanomedicine
• Cancer Therapeutics

Background:

• Conventional chemotherapy often uses multiple drugs, posing challenges in achieving optimal dosing due to individual drug pharmacokinetics.
• Developing advanced drug delivery systems is crucial for improving therapeutic efficacy and minimizing side effects in cancer treatment.

Purpose of the Study:

• To develop a supramolecular strategy for precisely controlling the loading ratio of two chemotherapeutic agents.
• To create a combination chemotherapy system for enhanced cancer treatment with reduced toxicity.

Main Methods:

• Formation of supramolecular aggregates using carboxylatopillar[6]arene (CP6A) and an oxaliplatin (Pt(iv) prodrug, PtC10).
• Encapsulation of doxorubicin (DOX) into PtC10-CP6A vesicles to form a ternary complex (DOX@PtC10⊂CP6A).
• Evaluation of drug release, antiproliferative effects on HepG-2 cells, and *in vivo* efficacy and toxicity in mice.

Main Results:

• The supramolecular system demonstrated pH-dependent release of both PtC10 and DOX in acidic environments.
• DOX@PtC10⊂CP6A exhibited synergistic antiproliferative effects against HepG-2 cancer cells.
• *In vivo* studies showed efficient tumor growth retardation and reduced drug-related toxicity in a mouse model.

Conclusions:

• The developed supramolecular system enables precise co-delivery of two chemotherapeutic agents.
• The ternary complex leverages the enhanced permeability and retention (EPR) effect for improved tumor targeting.
• This pH-responsive, combination chemotherapy approach offers a promising strategy for effective and safer cancer treatment.