Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

Targeted Theranostic Nano Vehicle Endorsed with Self‐Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe‐Out Tumor Reinitiating Cancer Stem Cells

The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug‐resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese‐doped mesoporous silica nanoparticle wit...

Full description

Saved in:
Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Vol. 16; no. 38; pp. e2003309 - n/a
Main Authors: Joseph, Manu M., Ramya, Adukkadan N., Vijayan, Vineeth M., Nair, Jyothi B., Bastian, Blossom T., Pillai, Raveendran K., Therakathinal, Sreelekha T., Maiti, Kaustabh K.
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01-09-2020
Subjects:
Biocompatibility
Biodegradation
Cancer
cancer stem cells
cancer theranostics
Cargo
Chitosan
Doxorubicin
drug resistance
Efflux
Folic acid
Hyaluronic acid
Manganese
mesoporous silica nanoparticles
Nanoparticles
Nanotechnology
Raman spectroscopy
Silicon dioxide
Stem cells
Toxicity
Xenotransplantation
mesoporous silica nanoparticles
biodegradation
cancer theranostics
cancer stem cells
drug resistance
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug‐resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese‐doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co‐loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual‐targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface‐enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN‐Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR‐positive syngeneic and CSC‐rich human xenograft murine models is associated with a tumor‐targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug‐loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe‐out of tumor reinitiating cancer stem cells. Here, the precise elimination of drug‐sensitive and resistant cancer cells along with cancer stem cells with the intelligent fabrication of a targeted theranostic nano vehicle (TTNV) is demonstrated. A tumor‐targeted biodistribution followed by a striking pattern of bioelimination of this TTNV contributes to the wipe‐out of tumor mass on both folate receptor‐positive and CD44‐positive tumor‐bearing mice.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202003309