The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo.

Int J Nanomedicine

Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China ; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.

Published: October 2016

Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372005PMC
http://dx.doi.org/10.2147/IJN.S79840DOI Listing

Publication Analysis

Top Keywords

thermosensitive liposomes
28
clotted plasma
20
plasma proteins
20
antitumor activity
12
tumor vessels
12
tumor stroma
12
proteins tumor
12
tumor
10
liposomes
8
vitro vivo
8

Similar Publications

Magnetic nanoparticles (MNPs) used for magnetic hyperthermia can not only damage tumor cells after elevating to a specific temperature but also provide the temperature required for thermosensitive liposomes (TSL) to release doxorubicin (DOX). MNPs injected into tumor will generate heat under an alternating magnetic field, so the MNPs distribution can determine temperature distribution and further affect the DOX concentration used for tumor therapy. This study proposes an asynchronous injection strategy for this combination therapy in order to improve the DOX concentration value for drug therapy, in which the MNPs are injected into tumor after a certain lagging of TSL injection in order to increase the TSL concentration inside tumor.

View Article and Find Full Text PDF

Thermosensitive liposome-encapsulated gold nanocages for photothermal-modulated drug release and synergistic photothermal therapy.

J Mater Chem B

January 2025

College of Chemistry and Materials Science, Chemical Biology Key Laboratory of Hebei Province, Hebei Research Center of the Basic Discipline of Synthetic Chemistry, Hebei University, Baoding, 071002, P. R. China.

Delivery nanosystems have been widely developed to improve the efficacy of chemotherapy. However, their performance regarding the non-specific leakage of drugs remained unsatisfactory. Herein, gold nanocages (AuNCs) were used as carriers and thermo-sensitive liposome (TSL) as a protective shell to design a camptothecin (CPT)-loaded delivery nanosystem (AuNCs/CPT@TSL) for photothermal-modulated drug release.

View Article and Find Full Text PDF

Novel thermosensitive small multilamellar lipid nanoparticles with promising release characteristics made by dual centrifugation.

Eur J Pharm Sci

December 2024

Institute of Pharmaceutical Sciences, University of Freiburg, 79104 Freiburg im Breisgau, Germany; Andreas Hettich GmbH, 78532 Tuttlingen, Germany. Electronic address:

Thermosensitive liposomes (TSLs) have great potential for the selective delivery of cytostatic drugs to the tumor site with greatly reduced side effects. Here we report the discovery and characterization of new thermosensitive small multilamellar lipid nanoparticles (tSMLPs) with unusually high temperature selectivity. Furthermore, the temperature-dependent release of the fluorescent marker calcein from tSMLPs is enhanced by human serum albumin.

View Article and Find Full Text PDF

Thermosensitive, injectable, antibacterial glabridin liposome/chitosan dual network hydrogel for diabetic wound healing.

Int J Biol Macromol

December 2024

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; Department of Traditional Chinese Medicine, Institute of Guangdong Geriatric, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.

Thermosensitive hydrogels show great potential in healing diabetic wounds, but they are still challenged by the long healing time, risk of infectivity, and accumulation of melanin. Herein, a dual network hydrogel is designed, which consists of chlorogenic acid (CA) modified chitosan (CS) (CA@CS), poly(N-isopropylacrylamide) (PNIPAm), and glabridin liposomes (GL). The gelation transition temperature of the hydrogel is 32-34 °C, which thus endows it with superior injectability at ambient temperature.

View Article and Find Full Text PDF

Near-Infrared Light-Activated DNA Nanodevice for Spatiotemporal In Vivo Fluorescence Imaging of Messenger RNA.

Anal Chem

December 2024

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.

Real-time visualization of messenger RNA (mRNA) is essential for tumor classification, grading, and staging. However, the low signal-to-background ratios and nonspatiotemporal specific signal amplification restricted the in vivo imaging of mRNA. In this study, a near-infrared (NIR) light-activated DNA nanodevice (DND) was developed for spatiotemporal in vivo fluorescence imaging of mRNA.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!