Abstract
Recently, cell-based immunotherapy has become one of the most promising ways to completely eliminate cancer. The major challenge is to effectively promote a proper immune response to kill the cancer cells by activated T cells. This study investigated the effect of T cell-mediated immunotherapy trigged by Au DENPs-MPC (zwitterion 2-methacryloyloxyethyl phosphorylcholine (MPC)-functionalized dendrimer-entrapped gold nanoparticles) loading oli-godeoxynucleotides (ODN) of unmethylated cytosine guanine dinucleotide (CPG). Here, we first synthesized Au DENPs-MPC, evaluated their capability to compress and transfect CpG-ODN to bone marrow dendritic cells (BMDCs), and investigated the potential to use T cells stimulated by matured BMDCs to inhibit the growth of tumor cells. The developed Au DENPs-MPC could apparently reduce the toxicity of Au DENPs, and enhanced transfer CpG-ODN to the BMDCs for the maturation as demonstrated by the 44.41–48.53% increase in different surface maturation markers. The transwell experiments certificated that ex vivo activated T cells display excellent anti-tumor ability, which could effectively inhibit the growth of tumor cells. These results suggest that Au DENPs-MPC can deliver CpG-ODN efficiently to enhance the antigen presentation ability of BMDCs to activate T cells, indicating that T cells-based immunotherapy mediated by Au DENPs-MPC loaded with CpG-ODN may become the most promising treatment of cancer.
Highlights
In the last few decades, immunotherapy has become an important and promising treatment for cancer [1,2], which can stimulate or boost our immune system to defend cancer cells in a much more robust and smarter manner [3]
We explored a novel T cell-based tumor immunotherapy induced by CpG-loaded zwitterion-functionalized Au DENPs
Compared with the group without any stimulation, the expression of bone marrow dendritic cells (BMDCs)’ maturation markers, CD80, CD86 and were remarkably raised to 51.23%, 45.44%, and 44.41%, respectively, indicating the BMDCs ensors 2022, 12, x FOR PEER REVIEW were matured after incubated with 50 μg/mL Au DENPs-MPC/CpG-ODN (Figure 3). 6 of
Summary
In the last few decades, immunotherapy has become an important and promising treatment for cancer [1,2], which can stimulate or boost our immune system to defend cancer cells in a much more robust and smarter manner [3]. Dendrimer-entrapped Au NPs (Au DENPs) showed more high gene delivery efficiency and lower cytotoxicity than it alone [27,28]. This is because of the truth that entrapped Au NPs can help to maintain the 3-dimensional spherical morphology of dendrimers, allowing more efficient compaction of DNA [29,30]. To reduce the nonspecific adsorption and improve the transport capacity to immune cells, the antifouling effect of the delivery vectors is worthy of attention. To enhance the efficiency of gene delivery, it is needed to remove the existence of serum protein in the medium. Au DENPs-MPC can be served as an efficient gene delivery vector and DCs stimulator, and bpeosteernvteiadllayseannhaefnficceieTncteglle-nmeeddeialitveedrytuvmecotroirmamnduDnoCtshesrtiampuylaafttoerr, laonaddipnogtewnittihalClypeGn-hOaDncNe. TItcaellsl-omperdoivaitdeedstaumgooordimremfeurennocteheforarpthyeafdteesriglonadofinbgiowseitnhsoCrps,Ga-nOdDbNro. aItdaelnssotphreoavpidpeliscaagtoioondfrieefledreonfcbeiofosernthsoerd. BBaasseeddoonntthheeaabboovvee rreessuullttss,, AAuu DDEENNPPss--MMPPCC//CCppGG ccoommpplleexxeesswwiitthhffiviveeddififfeferernent tnintir-otrgoegnepnhpohsopshpohruorsu(sN(/NP/)Pr)artiaotsio(s1,(12,, 42,, 64,, a6n, dan8d) w8)erweesreelescetleedctteodetvoaleuvaatleutahtee hthyedrhoyddyrnoadmy-ic nsaimzeicansdizzeetaanpdoteznettiaal.pTohteenatviaelr.agTehheyadvroedraygneamhiycdsriozedsyonfatmheicAusizDeEsNoPfs-tMhePCA/uCDpGE-NOPDsNMcoPmC/pClepxGe-sOwDeNrecaobmopulte2x0e0s wnmer,eaanbdouthte2ir00avnemra,gaendzetthaepirotaevnetriaaglsewzeetrae paobtoeuntti1a5lsmwVe,reas asbhoouwt 1n5inmVTa, balsesSh2o.wCnoinnsTidaebrliengS2t.hCeoonpsitdimerailngentdhoecoyptotismisael fefnicdieonccyytoasinsdefgfeicnieendceyliavnedry geefnfiecidenelciyve[3ry9,4e0ff]i,cwieencchyo[s3e9t,h40e]c,owmepclehxoessewthiteh caonmNp/lPexreastiowoitfh2afnorNth/ePsruabtisoeqoufe2ntfostrutdhiees. subsequent studies
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