Beyond hydrophilic polymers in amphiphilic polymer-based self-assembled NanoCarriers: Small hydrophilic carboxylate-capped disulfide drug delivery system and its multifunctionality and multispatial targetability

被引：12

作者：

Choi, Yeon Su ^{[1
]}

Cho, Hana ^{[1
]}

Choi, Won-Gu ^{[1
]}

Lee, Sung Su ^{[1
]}

Huh, Kang Moo ^{[2
]}

Shim, Min Suk ^{[3
]}

Park, In Suh ^{[4
]}

Cho, Yong-Yeon ^{[1
]}

Lee, Joo Young ^{[1
]}

Lee, Hye Suk ^{[1
]}

Kang, Han Chang ^{[1
]}

机构：

[1] Catholic Univ Korea, Coll Pharm, Dept Pharm, 43 Jibong ro, Bucheon 14662, Gyeonggi do, South Korea

[2] Chungnam Natl Univ, Dept Polymer Sci & Engn, 99 Daehak ro, Daejeon 34134, South Korea

[3] Incheon Natl Univ, Div Bioengn, 119 Acad ro, Incheon 22012, South Korea

[4] Inha Univ Hosp, Dept Pathol, 27 Inhang ro, Incheon 22332, South Korea

来源：

BIOMATERIALS | 2022年 / 280卷

基金：

新加坡国家研究基金会;

关键词：

Amphiphilic; Antibody-mediated adverse effect; Carboxylate-capped disulfide; Colloidal stability; Cytosolic targeting; pH targeting; PEGYLATION; CARRIERS; RELEASE; GLYCOL);

D O I：

10.1016/j.biomaterials.2021.121307

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic molecule-stabilized NPs for effective intra-cellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic molecule-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hy-drophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multi-ple disulfide-containing poly(epsilon-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic molecules represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers.

引用

页数：10

共 28 条

[11] The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors [J].