Synthesis of acid-activated reversible conversion supramolecular nanoplatform: application in drug delivery and anti-tumor activity

Supramolecular nanoplatforms with stimuli-responsive behavior feature sensitive performance and effective drug delivery, which are desirable as intelligent drug delivery systems. Generally, tumor cells are characterized by excessive acid production, resulting in a lower pH in the tumor microenvironment (pH < 6.5) than in normal tissues (pH ≈7.4) and providing the possibility for the drug delivery system to exploit this decrease in pH as a trigger for drug release. Here, an acid-sensitive supramolecular nanoplatform (CM-β-CD/FC₁₂⁺Br⁻ NPs) with assembly/disassembly properties was designed and constructed, which was exploited to capture, deliver, and release anti-tumor compound CSL. 2D NOESY was utilized to examine the host–guest interaction and the potential mechanism for CM-β-CD/FC₁₂⁺Br⁻ NPs loading CSL. CM-β-CD/FC₁₂⁺Br⁻ NPs present good blood compatibility. Cytotoxicity assay revealed that CSL-loaded NPs display minimal toxicity against normal cells BEAS-2B and good anticancer ability against five human cancer cell lines, especially for Human hepatoma cell line SMMC-7721. In addition, cell apoptosis and cycle assay further verified that CSL-loaded NPs-induced apoptosis in SMMC-7721 cells up to ~ 93%, as well as blocking the cells in G0/G1 phase and inhibiting the proliferation of SMMC-7721 cells in a dose-dependent manner. We expect that CM-β-CD/FC₁₂⁺Br⁻ NPs will be potential acid-answered drug delivery candidates.

Graphical Abstract

The acid-activated reversible conversion CM-β-CD/ FC₁₂⁺Br⁻ nanoparticles (NPs) are constructed to trap, deliver and release anti-liver cancer compound Celastrol (CSL). CSL-loaded NPs display a high release rate of CSL at the acidic environment within hepatoma cells, exhibit a high cytotoxicity and apoptotic rate for SMMC-7721 cells and arrest the cells at G0/G1 phase in a dose-dependent manner. CM-β-CD/ FC₁₂⁺Br⁻ NPs help to realize liver cancer treatment.