期刊
SMALL STRUCTURES
卷 3, 期 10, 页码 -出版社
WILEY
DOI: 10.1002/sstr.202200067
关键词
calixarene; drug delivery; molecular recognition; supramolecular chemistry; tumor accumulation
资金
- NSFC [U20A20259, 31961143004]
- Fundamental Research Funds for the Central Universities
- National Key Research and Development Programs of China [2018YFA0209700]
- NCC Fund [NCC2020FH04]
A new drug delivery paradigm based on supramolecular hierarchical recognition is proposed to achieve high tumor accumulation of anticancer drugs by overcoming challenges such as fast clearance or premature degradation, slow drug release kinetics, and nonspecific biodistribution. The formulation exhibits more efficient tumor accumulation than other PTX formulations, contributing to better therapeutic efficacy.
Promoting tumor accumulation of active pharmaceutical ingredients is crucial for targeted anticancer therapy. However, this issue has not yet been addressed because of the fast clearance or premature degradation, slow drug release kinetics, and nonspecific biodistribution of the reported formulations. Herein, a new drug delivery paradigm is proposed based on supramolecular hierarchical recognition to achieve high tumor accumulation of anticancer drugs by overcoming these three challenges. The prepared supramolecular ternary formulation of paclitaxel (PTX) contains two steps of molecular recognition: exogenous recognition of PTX by an artificial macrocyclic carrier, sulfonated azocalix[5]arene (SAC5A) in vitro, and endogenous recognition of PTX@SAC5A by intrinsic serum albumin in vivo. The ternary PTX@SAC5Acalbumin concurrently accomplishes prolonged blood circulation, rapid drug release, and dual passive and hypoxia-responsive targeting. As a result, the PTX@SAC5Acalbumin formulation exhibits more efficient tumor accumulation than free PTX and albumin-based, solvent based, liposome-based, and sulfobutyl ether-beta-cyclodextrin-based PTX formulations, thereby contributing to better therapeutic efficacy. The current strategy paves the way for promoting the tumor accumulation of drugs, showing the advantages of simplicity, universality, and reproducibility.
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