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A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
5954 450 2014 8 PDF Available
Title
A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers
Abstract

Here, we report a self-assembled polymeric micellar immunomodulator (SPI) for enhanced cancer treatment based on cationic amphiphilic polymers. To obtain the cationic amphiphilic polymer, the hydrophobic all-trans-retinoic acid (ATRA) was conjugated with a hydrophilic low-molecular-weight PEI (LowPEI, Mn = 1.8 kDa). The ATRA–LowPEI conjugates could self-assemble in aqueous media, forming micelles with a strong positive charge (∼+40 mV) and particle sizes of ∼70 nm. Compared to conventional therapeutic agents (e.g., cisplatin), the SPI exhibited enhanced anti-cancer activity regardless of drug resistance. After mechanistic in vitro cell death studies, we revealed that the mechanical disruptive force generated by the cationic charge of SPI primarily induced necrotic cell death. Furthermore, the organelle fragments induced by the necrotic cell death triggered antitumoral immune responses. Therefore, SPI induced synergistic effects of the cationic charge-induced necrosis and antitumoral immune responses could produce an effective cancer treatment. In addition, the SPI was shielded by hyaluronic acid (HA/SPI complex) to enhance its tumor selectivity in vivo. Finally, the HA/SPI complex accumulated selectively into tumor sites after systemic administration into tumor-bearing mice, exhibiting effective antitumoral effects without systemic toxicity. Therefore, this technology holds great potential for translation into a clinical cancer treatment.

Keywords
Cancer; Cationic polymer; Self-assembly; Necrosis; Antitumor immune responses
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A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 37, December 2014, Pages 9912–9919
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us