دورية أكاديمية
أعرض في EDS

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy.

التفاصيل البيبلوغرافية
العنوان: Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy.
المؤلفون: Su J; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China., Wu C; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China., Zou J; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China., Wang X; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China., Yang K; School of Pharmacy, University of Auckland, Private Bag 92019, Auckland, New Zealand., Liu J; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China., Wu Z; School of Pharmacy, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: z.wu@auckland.ac.nz., Zhang W; Department of Pharmaceutics, China Pharmaceutical University, Jiangsu 210009, PR China. Electronic address: zwllz@163.com.
المصدر: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Aug; Vol. 372, pp. 69-84. Date of Electronic Publication: 2024 Jun 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
مواضيع طبية MeSH: Liposomes* , Transcytosis* , Hyaluronic Acid*/chemistry , Antineoplastic Agents*/administration & dosage , Antineoplastic Agents*/pharmacology , Protamines*/chemistry, Animals ; Humans ; Cell Line, Tumor ; Female ; Mice, Inbred BALB C ; Endothelial Cells/metabolism ; Endothelial Cells/drug effects ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Mice ; Drug Liberation
مستخلص: Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87-2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-L BAY ) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-L BAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-L BAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-L BAY ). In addition, more HA-P-L BAY was retained in tumor cells (4T1) compared to HA/P-L BAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-L BAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-L BAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Active trans-endothelial transport; Chemical crosslinking liposomes; Fine-tuning of liposome integrity; Improved trans-endothelial nano-structural integrity; Intracellular aggregation; Prolonged tumor retention
المشرفين على المادة: 0 (Liposomes)
9004-61-9 (Hyaluronic Acid)
0 (Antineoplastic Agents)
0 (Protamines)
تواريخ الأحداث: Date Created: 20240612 Date Completed: 20240727 Latest Revision: 20240728
رمز التحديث: 20240729
DOI: 10.1016/j.jconrel.2024.06.025
PMID: 38866244
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4995
DOI:10.1016/j.jconrel.2024.06.025