High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles Driven by Donor–Receptor Coordination Interactions

Abstract

Polymeric micelles are extensively used for the delivery of hydrophobic drugs, which, however, suffer from unsatisfactory drug loading, colloidal uniformity, formulation stability, and drug release. Herein, we demonstrate a convenient strategy to prepare micelles with ultrahigh drug loading via the incorporation of polymer-drug coordination interactions. An amphiphilic copolymer containing pendant phenylboronic acid as electron acceptor unit was synthesized, which afforded donor-acceptor coordination with doxorubicin to obtain micelles with ultrahigh drug loading (∼50%), nearly quantitative loading efficiency (>95%), uniform size, and colloidal stability. Besides, the encapsulated drug can be effectively and selectively released in response to the high reactive oxygen species levels in cancer cells, which potentiated the anticancer efficacy and reduced systemic toxicity. Apart from doxorubicin, the current platform could be extended to other drugs with electron-donating groups (e.g., epirubicin and irinotecan), rendering a simple and robust strategy for enabling high drug loading in polymeric micelles and cancer-specific drug release.

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

“…Of note, typically when amphiphilic copolymers encapsulate small and hydrophobic drugs, it is found out lower drug loading and encapsulation efficiency of nanoparticles . This outcome may be largely attributed to the formation of large drug aggregates, through long‐range‐ordered drug molecule packing.…”

Boronic acid-rich dendrimer for efficient intracellular peptide delivery

“…Here, we developed a boronic acid-rich cationic dendrimer for efficient internalization of peptides into different cell lines. Boronic acid is an electron deficient group which could interact with the electron-rich residues on the peptides such as amine and hydroxyl groups via coordination bonding between Lewis acid and base [39][40][41][42][43]. In addition, the cationic dendrimer could bind with anionic groups of cargo peptides via ionic interactions.…”

Shell‐Sheddable Poly(N‐2‐hydroxypropyl methacrylamide) Polymeric Micelles for Dual‐Sensitive Release of Doxorubicin

“…For efficient cancer therapy, it is often more desirable to accomplish rapid drug release after micelles arriving at the tumor tissue, which may enhance the therapeutic efficacy and reduce drug resistance in cells. To this end, various stimuli‐sensitive micelles have been reported to release drugs quickly in response to an appropriate endogenous or exogenous stimulus including temperature, pH, redox, reactive oxygen species, and enzymes . In particular, reduction‐sensitive polymers have received extensive interests for intracellular drug delivery due to the high difference in the redox potential between extracellular matrix and the intracellular fluids .…”