Biodegradable Nanoparticles of Polyacrylic Acid–Stabilized Amorphous CaCO3 for Tunable pH‐Responsive Drug Delivery and Enhanced Tumor Inhibition. (10th April 2019)

• Record Type: Journal Article
• Authors: Xu, Chengyuan; Yan, Yunfeng; Tan, Jinchao; Yang, Dahai; Jia, Xianjing; Wang, Lu; Xu, Yisheng; Cao, Song; Sun, Shengtong
• Is Part Of: Advanced functional materials. Volume 29:Number 24(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-10
• Subjects: amorphous calcium carbonate -- biodegradation -- drug delivery -- pH‐responsive -- tumor inhibition; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201808146
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Inorganic nanoparticles (NPs) are promising drug delivery carriers owing to their high drug loading efficiency, scalable preparation, facile functionalization, and chemical/thermal stability. However, the clinical translation of inorganic nanocarriers is often hindered by their poor biodegradability and lack of controlled pH response. Herein, a fully degradable and pH‐responsive DOX@ACC/PAA NP (pH 7.4–5.6) is developed by encapsulating doxorubicin (DOX) in poly(acrylic acid) (PAA) stabilized amorphous calcium carbonate (ACC) NPs. The DOX‐loaded NPs have small sizes (62 ± 10 nm), good serum stability, high drug encapsulation efficiency (>80%), and loading capacity (>9%). By doping proper amounts of Sr 2+ or Mg 2+, the drug release of NPs can be further modulated to higher pH responsive ranges (pH 7.7–6.0), which enables drug delivery to the specific cell domains of tissues with a less acidic microenvironment. Tumor inhibition and lower drug acute toxicity are further confirmed via intracellular uptake tests and zebrafish models, and the particles also improve pharmacokinetics and drug accumulation in mouse xenograft tumors, leading to enhanced suppression of tumor growth. Owing to the excellent biocompatibility, biodegradability, and tunable drug release behavior, the present hybrid nanocarrier may find broad applications in tumor therapy. Abstract : The clinical translation of inorganic nanocarriers is often hindered by poor biodegradability and lack of a controlled pH response. Here reported is a fully degradable hybrid nanoparticle consisting of polyacrylic acid and amorphous CaCO3 that can efficiently encapsulate doxorubicin and exhibit apparent pH responsiveness of drug release. By doping Sr 2+ or Mg 2+, drug release at slightly higher pH ranges is realized.