Programmable delivery of immune adjuvant to tumor-infiltrating dendritic cells for cancer immunotherapy.
2020
Tumor-infiltrating dendritic cells
(TIDCs) are mostly immature
and immunosuppressive, usually mediating immune inhibition. The utilization
of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate
the activation of TIDCs has been demonstrated to be effective for
improving antitumor immunity. However, a series of biological barriers
has limited the efficacy of previous nanocarriers for delivering CpG
to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based
nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the
tumor acidity triggers the rapid release of CpG conjugated polyamidoamine
(PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion
deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive
condition of the endolysosomes led to the subsequent release of CpG,
which promotes the DCs activation and enhances antitumor immunotherapies.
Programmable delivery of immune adjuvant efficiently overcomes the
barriers for targeted delivery to TIDCs and provides a promising strategy
for improving cancer immunotherapy.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
29
References
15
Citations
NaN
KQI