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Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
544 46 2013 10 PDF Available
Title
Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy
Abstract

Conventionally used adjuvants alone are insufficient for triggering cell-mediated immunity, although they have been successfully developed to elicit protective antibody responses in some vaccines. Here, with the aim of eliciting cell-mediated immunity, pathogen-associated molecular patterns (PAMPs) were immobilized with apatite within the pores and on the surface of mesoporous silica (MS) with particle sizes from 30 to 200 nm to prepare novel MS-Ap-PAMP adjuvants, which showed cell-mediated anti-tumor immunity that was markedly improved compared to commercial alum adjuvant in vitro and in vivo. The toxicity and antitumor immunity of the MS-Ap-PAMP adjuvants were evaluated in vitro and in vivo. MS with a particle size of 200 nm showed minimum in vitro cytotoxicity to NIH3T3 cells, particularly at concentrations no higher than 100 μg ml−1. In particular, apatite precipitation within the pores and on the surface of MS decreased the in vitro cytotoxicity of MS particles. The MS-Ap-PAMP adjuvants showed the maximum in vitro immunogenic activity among original culture medium, PAMP and alum-PAMP. Moreover, injection of the MS-Ap-PAMP adjuvant in combination with liquid-nitrogen-treated tumor tissue (derived from Lewis lung carcinoma cells) into C57BL/6 mice markedly inhibited in vivo tumor recurrence and the development of rechallenged tumor compared to those with commercial alum adjuvant. The MS-Ap-PAMP adjuvant contributed to the elicitation of a potent systemic antitumor immunity without obvious toxicity in vivo.

Keywords
Immune therapy; Cancer; Adjuvant; Mesoporous silica; Pathogen-associated molecular patterns
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Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 9, Issue 7, July 2013, Pages 7480–7489
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