%0 Journal Article
%T Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy
%A Dongyang Zhao
%A Haotian Zhang
%A Huicong Zhang
%A Jin Sun
%A Lu Xu
%A Lu Zhong
%A Qiming Kan
%A Qingsong Li
%A Yanying Liu
%A Yongjun Wang
%A Zhenbao Li
%J Archive of "Acta Pharmaceutica Sinica. B".
%D 2019
%R 10.1016/j.apsb.2018.11.006
%X Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution
%K ADA
%K 1-adamantane carboxylic acid
%K AD-B-PEG
%K the pH-responsive adamantane-PEG conjugate
%K AD-O-PEG
%K the non-pH sensitive adamantane-PEG conjugate
%K AUC
%K area under the plasma concentration¡ªtime curve
%K CLSM
%K confocal laser scanning microscope
%K DAPI
%K 2-(4-amidinophenyl)-6-indolecarbamidine dihydrochloride
%K DCC
%K N
%K N¡ä-dicyclohexylcarbodiimide
%K DCM
%K dichloromethane
%K DDS
%K drug delivery systems
%K DiR
%K 1
%K 1¡ä-dioctadecyltetramethyl indotricarbocyanine iodide
%K DL
%K drug-loading content
%K DLS
%K dynamic light scattering
%K DMAP
%K 4-dimethylaminopyrideine
%K DMEM
%K Dulbecco£¿s modified Eagle£¿s medium
%K Dox¡¤HCl
%K doxorubicin hydrochloride
%K Dox/HCVBP
%K Dox-loaded hyaluronic acid-based transformable supramolecular nanoplatform
%K Dox/HCVOP
%K Dox-loaded hyaluronic acid-based untransformable supramolecular nanoplatform
%K EDC
%K 1-ethyl-3-(3-dimethyalminopropl) carbodiimide
%K EE
%K encapsulation efficiency
%K FBS
%K fetal bovine serum
%K HA
%K hyaluronic acid
%K HA-CD
%K hydroxypropyl-¦Â-cyclodextrin grafted hyaluronic acid polymer
%K HCBP
%K hydroxypropyl-¦Â-cyclodextrin grafted hyaluronic acid polymer and pH-responsive adamantane-PEG conjugate inclusion complex
%K HCPs
%K hydroxypropyl-¦Â-cyclodextrin grafted hyaluronic acid polymer and adamantane-PEG conjugate inclusion complexes
%K HEPES
%K 4-(2-hydroxyethyl)-1-piperazineethanesul-fonic acid
%K H&E
%K hematoxylin and eosin
%K HOBT
%K 1-hydroxybenzotriazole
%K HPCD
%K hydroxypropyl-¦Â-cyclodextrin
%K MW
%K molecular weight
%K NPs
%K nanoparticles
%K PCC
%K Pearson£¿s correlation coefficient
%K PDI
%K polydispersity index
%K pHe
%K the extracellular pH
%K RES
%K reticuloendothelial system
%K RPMI-1640
%K Roswell Park Memorial Institute-1640
%K THF
%K tetrahydrofuran
%K TUNEL
%K terminal deoxynucleotidyl transferased dUTP nick end labeling
%K VES
%K vitamin E succinate Hyaluronic acid
%K Benzoic imine linkage
%K Active-targeting
%K Cancer therapy
%K Natural ligand
%K Supramolecular nanoplat-form
%K Transformative nanoparti-cles
%K PEG dilemma
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437598/