Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma

Autor: Yingying Chi, Shuaishuai Feng, Xuelei Yin, Jinhu Liu, Zimei Wu, Chuanyou Guo, Kaoxiang Sun
Rok vydání: 2018
Předmět:
Male
Time Factors
Oligosaccharides
Pharmaceutical Science
Chitin
02 engineering and technology
Polyethylene Glycols
chemistry.chemical_compound
0302 clinical medicine
polycyclic compounds
Tissue Distribution
Cationic liposome
Mice
Inbred BALB C
Liposome
Antibiotics
Antineoplastic
reduction-sensitivity
General Medicine
021001 nanoscience & nanotechnology
Glutathione
Tumor Burden
Cholesterol
Receptors
Estrogen
030220 oncology & carcinogenesis
Injections
Intravenous
Osteosarcoma
0210 nano-technology
Research Article
Estrone
medicine.drug_class
Drug Compounding
Mice
Nude
Bone Neoplasms
chotooligosaccharides
cationic liposomes
03 medical and health sciences
estrogen-functionalized
Cell Line
Tumor
osteosarcoma
medicine
Animals
Humans
Technology
Pharmaceutical
Particle Size
targeting
Chitosan
lcsh:RM1-950
technology
industry
and agriculture
Cationic polymerization
medicine.disease
Biocompatible material
Xenograft Model Antitumor Assays
Drug Liberation
lcsh:Therapeutics. Pharmacology
chemistry
Doxorubicin
Estrogen
Liposomes
Cancer research
Zdroj: Drug Delivery, Vol 25, Iss 1, Pp 900-908 (2018)
Drug Delivery
ISSN: 1521-0464
1071-7544
DOI: 10.1080/10717544.2018.1458920
Popis: An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain to achieve estrogen receptor-targeting. The liposomal carriers were prepared by the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX) was loaded with ammonium sulfate gradient. The physicochemical properties, reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor-targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an average size about 110 nm, and high encapsulation efficiency. The liposomes were stable in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional liposomes selectively accumulated in the MG63 xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the tumor growth and enhanced the animal survival rate. Overall, the COS grafted estrogen-functionalized cationic liposomes, fortified with glutathione-responsiveness, showed great potential for specific intracellular drug delivery to estrogen receptor-expressing tumors such as osteosarcoma.
Databáze: OpenAIRE
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