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

Abstract

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 photothermal therapy (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 bone marrow-derived dendritic cells (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.

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“…Then, the LE of ICG in ICG@PSMA NPs was calculated to be 6.2%, which is comparable to many other different types of polymer encapsulated ICG nanoparticles, such as H-PMOF (17.4%), 27 CMCh-BAPE-RGD@ICG Nanoparticles (7.5%), 28 PLGA-ICG-R848 NPs ((0.82 ± 0.03)%). 49 …”

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“…In this case, the NK cells become irreplaceable as they can recognize tumor cells and mount a rapid immune response without antibodies or MHC [38]. Wenfeng Lin et al reported that PLGA-ICG-R848 after laser irradiation can stimulate the increased number of NK cells and generate an anti-tumor immune response via secretion of chemokines and cytokines, but HNP as a PTT material on the activation of NK cells has not yet been reported [39,40]. In terms of mechanism, we also explored the effect of HNP on NK cells under 808 nm laser irradiation.…”

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“…111 The systemic toxicity with these two main metabolites is minimal because they are efficiently cleared from the body. 112…”