The average size of the CD@R848@NPs was 376 ± 30 nm with a surface charge of 21 ± 1 mV.
The delivery system utilizes the targeting ability of to direct R848 to tumor-supporting M2-like macrophages.
The combination of CD@R848@NPs with an anti-TNFR2 antibody may reduce the proportion of regulatory T cells (Tregs).
CD@R848@NPs demonstrated increased penetration in tumor tissues compared to plain PLGA nanoparticles or R848.
This formulation could dramatically reprogram M1-like macrophages and remove tumors.
The new nanocapsule system is associated with prolonged survival in a colon adenocarcinoma model.
Simplified
PURPOSE: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of (2-HP-β-CD).
METHODS: R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo.
RESULTS: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival.
CONCLUSION: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming , and enhancement immunotherapy.
Key numbers
376 ± 30 nm
Average Size of Nanoparticles
Size of CD@R848@NPs measured in nanometers.
21 ± 1 mV
Surface Charge of Nanoparticles
Zeta potential of CD@R848@NPs measured in millivolts.
not specified
Prolonged Survival
Survival benefits observed in treated mice compared to control groups.
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