Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Apr 21, 2021International journal of nanomedicine

PLGA Nanoparticles Carrying Indocyanine Green and Resiquimod for Prostate Cancer Treatment

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Abstract

PLGA-ICG-R848 nanoparticles significantly decreased RM9 cell viability to 3.9±1.0% after laser irradiation.

PLGA-ICG-R848 nanoparticles have a mean diameter of 157.7 nm and showed no cytotoxic effect in prostate cancer cells.
These nanoparticles promoted the maturation of , increasing the proportions of CD11c+CD86+ and CD11c+CD80+ cells.
In a mouse model, PLGA-ICG-R848-based laser ablation led to a significant inhibition of prostate cancer growth as indicated by decreased bioluminescent signals.
The ratio of splenic natural killer cells in the PLGA-ICG-R848 group was 3.96±1.88%, compared to 0.99±0.10% in the control group, suggesting an enhanced immune response.

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PURPOSE: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment.

METHODS: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation.

RESULTS: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa.

CONCLUSION: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

Key numbers

(3.9±1.0)%

Cell Viability Reduction

Viability of RM9 prostate cancer cells after treatment with nanoparticles and laser.

(3.96±1.88)%

NK Cell Ratio Increase

Proportion of splenic NK cells after PLGA-ICG-R848 treatment compared to control.

(65.71±9.14)%

BMDC Maturation Markers

Proportion of CD11c+CD86+ cells in treated with PLGA-ICG-R848.

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Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

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