Format

Send to

Choose Destination
Acta Biomater. 2017 Apr 15;53:414-426. doi: 10.1016/j.actbio.2017.02.030. Epub 2017 Feb 16.

Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

Author information

1
College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
2
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
3
Biogenics Inc., Daejeon 34027, Republic of Korea.
4
Biogenics Inc., Daejeon 34027, Republic of Korea; Skin & Tech Inc., Seongnam, Gyeonggi 13135, Republic of Korea.
5
Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Suwon, Gyeonggi 16229, Republic of Korea.
6
College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea; Convergence Research Center for Functional Plant Products, Advanced Institutes of Convergence Technology, Suwon, Gyeonggi 16229, Republic of Korea. Electronic address: hjko@kangwon.ac.kr.
7
College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.

Abstract

(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic acid-sialic acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.

KEYWORDS:

Hyaluronic acid-ceramide; Nanoparticle; Phenylboronic acid; Tumor penetration; Tumor targeting

PMID:
28216300
DOI:
10.1016/j.actbio.2017.02.030
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center