Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy

Abstract

In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy.

Zn-Dipicolylamine-Based ROS-Responsive Bola-Lipid Nanoparticles for Efficient Protein Delivery and Tumor Immunotherapy

“…Primary bone marrow-derived dendritic cells (BMDCs) were prepared as described previously. 53 Briefly, bone marrow cells were obtained from femur and tibia of C57BL/6 mice by rinsing with RPMI 1640 medium and then cultured in RPMI 1640 medium supplemented with 10% of FBS, 1% of penicillin−streptomycin, 10 ng/mL of IL-4, and 20 ng/mL of GM-CSF. The obtained cells were cultured for 7 days, and the medium was changed by 5 mL every 2 days.…”

Amphiphilic acetylacetone-based carbon dots

“…18 Moreover, methods for fabricating bright amphiphilic CDs are still in their infancy. 19 The amphiphilicity of CDs can be introduced via post-synthetic surface modification with long hydrophobic chain epoxides or acrylamides, as was recently shown in a study by Chen et al 20 Another example is the synthesis of CDs in acetone, which mixes well with both polar and non-polar solvents. 14 For most of the reported hydrophobic or amphiphilic CDs, 10,16,17,20–25 the PL bands experienced shifts with the change in polarity of the medium.…”

A Fluorescent Vector of Carbon Dot to Deliver Rab13 and Rab14 Plasmids for Promoting Neurite Outgrowth

“…32,35−39 Functionalized CDs have been demonstrated to provide multiple abilities of multimodal imaging, tumor targeting, and therapeutic nucleic acid delivery in tumor immunotherapy. 40,41 Furthermore, CDs can be doped with the probes used in magnetic resonance imaging (MRI) and computed tomography to improve the imaging quality for performing imaging guidance therapy. 38,39,42,43 Moreover, ZnCl 2 can be used as a pyrolysis-promoting agent to transform O and N precursors in organic solvents into crystalline CDs, which can produce superoxide radicals (O 2…”

“…However, surface-specific functionalization and ligand modification can endow CDs with targeting capability and also improve their duration of therapeutic retention. − Moreover, the solubility of hydrophobic therapeutic reagents in water is enhanced by transporting them with CDs. , Thus, CDs have been used as nanocarriers for cancer therapy in many studies. They have been used to deliver targeted anticancer drugs, such as curcumin, doxorubicin, cisplatin­(IV), and docetaxel, to tumor cells and can be used to achieve synergistic treatment through multidrug delivery with high blood compatibility in intravenous therapy. ,− Functionalized CDs have been demonstrated to provide multiple abilities of multimodal imaging, tumor targeting, and therapeutic nucleic acid delivery in tumor immunotherapy. , Furthermore, CDs can be doped with the probes used in magnetic resonance imaging (MRI) and computed tomography to improve the imaging quality for performing imaging guidance therapy. ,,, Moreover, ZnCl 2 can be used as a pyrolysis-promoting agent to transform O and N precursors in organic solvents into crystalline CDs, which can produce superoxide radicals (O 2 ·– ) upon light illumination and successfully reduce tumor size through photodynamic therapy . Mn-CDs synthesized using the precursor manganese­(II) phthalocyanine act as a H 2 O 2 -driven oxygenator to produce singlet oxygen efficiently for photodynamic therapy and exhibit multiple advantages in image-guided therapy, including the ability to achieve near-infrared fluorescence imaging as well as high relaxivity in MRI .…”