Small
Small
4 years ago

Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy

Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy
Yongzhuo Huang, Beihua Xu, Ying Hu, Jiaojiao Xu, Yunxu Yang, Jin Tao
This work aims at developing an immunotherapeutic strategy to deliver a cancer DNA vaccine targeting dendritic cells (DCs), to trigger their maturation and antitumor function, and reduce immune escape using a polymeric nanocomplex of paclitaxel (PTX)-encapsulated sulfobutylether-β-cyclodextrin (SBE)/mannosylated N,N,N-trimethylchitosan (mTMC)/DNA. To enhance DC-targeting and revoke immunosuppression is the major challenge for eliciting effective antitumor immunity. This codelivery system is characterized by using low-dose PTX as an adjuvant that is included inside SBE, and the PTX/SBE further serves as an anionic crosslinker to self-assemble with the cationic mTMC/DNA polyplexes. This system is used in combination with a microneedle for transcutaneous vaccination. Once penetrating into the epidermis, the mannosylated nanocomplexes would preferentially deliver the pTRP-2 DNA vaccine inside the DCs. Phenotypic maturation is demonstrated by the increased expression of costimulatory molecules of CD80 and CD86, and the elevated secretion of IL-12p70. The mixed leucocyte reactions reveal that the PTX/SBE-mTMC/DNA nanocomplexes enhance the proliferation of CD4+ and CD8+ T cells, and inhibit the generation of immune-suppressive FoxP3+ T cells. The system shows high antitumor efficacy in vivo. The PTX/SBE-mTMC/DNA nanocomplexes for DC-targeted codelivery of DNA vaccine and adjuvant PTX yield synergistic effects on the DC maturation and its presenting functions, thus increasing immune stimulation and reducing immune escape. Paclitaxel-based therapy possesses dose-dependent Yin-and-Yang nature. Normal dose impairs the immune system, while low dose displays the adjuvant function for stimulating immune responses and promoting the maturation of dendritic cells (DCs). A polymeric nanoassembly system is proposed for microneedle-assisted codelivery of a pTRP-2 vaccine targeting the epidermis DCs and the imunomodulator low-dose paclitaxel for enhanced cancer immunotherapy.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/smll.201700666

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.