Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer

Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superpara...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2018-02, Vol.29 (2), p.275-286
Main Authors: Manigandan, Amrutha, Handi, Vandhana, Sundaramoorthy, Niranjana Sri, Dhandapani, Ramya, Radhakrishnan, Janani, Sethuraman, Swaminathan, Subramanian, Anuradha
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - therapeutic use
Breast cancer
Cages
Cancer
Cell Line, Tumor
Cells
Chitosan
Chitosan - chemistry
Conjugation
Coordination compounds
Diagnostic systems
Doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - therapeutic use
Drug Delivery Systems
Drug resistance
Female
Fibrosis
Humans
Hyperthermia
Immigration
Immunoconjugates - administration & dosage
Immunoconjugates - therapeutic use
Internalization
Iron oxides
Magnetic fields
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Magnetite Nanoparticles - chemistry
Membrane potential
Metastases
Mice, Inbred BALB C
Mice, Nude
Micelles
Mitochondria
Nanoparticles
pH effects
Precision medicine
Theranostic Nanomedicine - methods
Transmission electron microscopy
Triple Negative Breast Neoplasms - diagnostic imaging
Triple Negative Breast Neoplasms - drug therapy
Vitamin E
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.7b00577