Mannose-Functionalized Biodegradable Nanoparticles Efficiently Deliver DNA Vaccine and Promote Anti-tumor Immunity
Autor: | Yanheng Wu, Zhi Ping Xu, Xiaohui Zhao, Bing Sun, Jie Liu, Wenyi Gu, Jingjing Wang, Fatemeh Movahedi, Pei Cao |
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Rok vydání: | 2021 |
Předmět: |
Calcium Phosphates
Materials science medicine.medical_treatment media_common.quotation_subject Antigen presentation 02 engineering and technology Cancer Vaccines DNA vaccination 03 medical and health sciences Cancer immunotherapy Antigen Immunity Cell Line Tumor Neoplasms Vaccines DNA medicine Animals Humans General Materials Science Internalization 030304 developmental biology media_common Drug Carriers 0303 health sciences Diphosphonates biology Immunotherapy 021001 nanoscience & nanotechnology 3. Good health Mice Inbred C57BL Ovalbumin Cancer research biology.protein Nanoparticles 0210 nano-technology Mannose |
Zdroj: | ACS Applied Materials & Interfaces. 13:14015-14027 |
ISSN: | 1944-8252 1944-8244 |
Popis: | Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the low stability, ineffective cell internalization, and low immunostimulation hinder their wide application. Thus, developing targeted and safe systems to effectively deliver DNA vaccines becomes a vital step. In this study, we report the development of mannose- and bisphosphonate (BP)-modified calcium phosphate (CP) nanoparticles (NPs) as efficient vaccine delivery vehicles by targeting C-type lectin receptors (CLRs) on antigen-presenting cells (APCs). Using a model antigen ovalbumin (OVA)-encoded plasmid DNA (pOVA) as a model vaccine, we demonstrate that mannose-modified and BP-stabilized CP (MBCP) nanoparticles are mono-dispersed for enhanced uptake by APCs and subsequently induce OVA antigen presentation and immunostimulation. Mice immunized with MBCP-pOVA nanovaccines show a significantly stronger anti-OVA antibody response with a quicker IgG1 and IgG2a antibody production than unmodified NPs. Moreover, MBCP-pOVA immunization significantly inhibits the growth of OVA-expressing E.G7 tumor cells in C57BL/6J mice. Our data collectively suggest that the modifications to enhance the stability and targeting ability of MBCP NPs are essential for effective delivery of DNA vaccines and promote robust anti-tumor immunity. |
Databáze: | OpenAIRE |
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