Hybrid PEGylated chitosan/PLGA nanoparticles designed as pH-responsive vehicles to promote intracellular drug delivery and cancer chemotherapy

Sheng-Jyun Huang; Tzu-Hao Wang; Ya-Hsuan Chou; Hui-Min David Wang; Tsai-Ching Hsu; Jia-Le Yow; Bor-Show Tzang; Wen-Hsuan Chiang

doi:10.1016/j.ijbiomac.2022.04.209

Hybrid PEGylated chitosan/PLGA nanoparticles designed as pH-responsive vehicles to promote intracellular drug delivery and cancer chemotherapy

Int J Biol Macromol. 2022 Jun 15:210:565-578. doi: 10.1016/j.ijbiomac.2022.04.209. Epub 2022 May 2.

Authors

Sheng-Jyun Huang¹, Tzu-Hao Wang¹, Ya-Hsuan Chou¹, Hui-Min David Wang², Tsai-Ching Hsu³, Jia-Le Yow⁴, Bor-Show Tzang⁵, Wen-Hsuan Chiang⁶

Affiliations

¹ Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan.
² Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung 402, Taiwan.
³ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
⁴ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
⁵ Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: bstzang@csmu.edu.tw.
⁶ Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: whchiang@dragon.nchu.edu.tw.

PMID: 35513093
DOI: 10.1016/j.ijbiomac.2022.04.209

Abstract

To achieve effective intracellular anticancer drug release for boosted antitumor efficacy, the acidity-responsive nanovehicles for doxorubicin (DOX) delivery were fabricated by tailor-made co-assembly of amphiphilic PEGylated chitosan_20k and hydrophobic poly(lactic-co-glycolic acid) (PLGA) segments at pH 8.5. The attained DOX-loaded PEGylated chitosan_20k/PLGA nanoparticles (DOX-PC_20kPNs) were characterized to have a spherical shape composed of drug-encapsulated chitosan_20k/PLGA-constituted solid core surrounded by hydrophilic PEG shells. Compared to non-pH-sensitive DOX-loaded PLGA nanoparticles (DOX-PNs), the DOX-PC_20kPNs displayed outstanding colloidal stability under serum-containing condition and tended to swell in weak acidic milieu upon increased protonation of chitosan_20k within hybrid cores, thus accelerating drug release. The in vitro cellular uptake and cytotoxicity studies revealed that the DOX-PC_20kPNs after being endocytosed by prostate TRAMP-C1 cancer cells rapidly liberated drug, thus promoting drug accumulation in nuclei to enhance anticancer potency. Moreover, the hydrated PEG shells of DOX-PC_20kPNs remarkably reduced their uptake by macrophage-like RAW264.7 cells. Importantly, in vivo animal findings showed that the DOX-PC_20kPNs exhibited the capability of inhibiting TRAMP-C1 tumor growth superior to free hydrophobic DOX molecules and DOX-PNs, demonstrating the great potential in cancer chemotherapy.

Keywords: Acidity-responsive nanovehicles; PEGylated chitosan; cancer chemotherapy.

MeSH terms

Animals
Antineoplastic Agents* / pharmacology
Chitosan* / chemistry
Doxorubicin / chemistry
Drug Carriers / chemistry
Drug Delivery Systems
Drug Liberation
Hydrogen-Ion Concentration
Male
Nanoparticles* / chemistry
Neoplasms*
Polyethylene Glycols / chemistry

Substances

Antineoplastic Agents
Drug Carriers
Polyethylene Glycols
Doxorubicin
Chitosan