Trojan Horse Monocyte-Mediated Delivery of Conjugated Polymer Nanoparticles for Improved Photodynamic Therapy of Glioblastoma

Abstract

Aim: To assess monocyte-based delivery of conjugated polymer nanoparticles (CPNs) for improved photodynamic therapy (PDT) in glioblastoma (GBM). Materials & methods: Human monocyte cells (THP-1) and murine monocytes isolated from bone marrow (mBMDMs) were employed as stealth CPN carriers to penetrate into GBM spheroids and an orthotopic model of the tumor. The success of PDT, using this cell-mediated targeting strategy, was determined by its effect on the spheroids. Results: CPNs did not affect monocyte viability in the absence of light and did not show nonspecific release after cell loading. Activated monocytes incorporated CPNs in a higher proportion than monocytes in their naive state, without a loss of cellular functionality. In vitro PDT efficacy using cell-mediated delivery was superior to that using non vehiculized CPNs. Conclusion: CPN-loaded monocytes could efficiently deliver CPNs into GBM spheroids and the orthotopic model. Improved PDT in spheroids was confirmed using this delivery strategy.

Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors

“…Besides, the introduction of rare biological metals such as Ni (IONPs) or Pt (PtOEP) gives us the opportunity to quantify the CPN content in tissues using more sensitive techniques like ICP-MS in the near future [ 32 ]. Our groups have previously developed metallated porphyrin-doped CPNs with outstanding performance in PDT for the eradication of GBM tumor cells in vitro [ 8 , 9 , 10 ]. With the aim of a potential clinical therapeutic application of this type of particles, their preclinical biodistribution evaluation in animal models is mandatory particularly considering that pharmacokinetics and tumor accumulation information for these materials is extremely limited.…”

“…Aimed to this, our group has recently developed metallated porphyrin-doped conjugated polymer nanoparticles (CPNs) for highly efficient photodynamic therapy (PDT), a therapeutic approach of growing interest in the treatment of GBM and the prevention of local tumor recurrence [ 7 ]. These CPNs have been shown to be effective at eliminating glioma tumor cells through ROS-induced apoptotic damage thus highlighting their potential use in photo-assisted treatment of GBM [ 8 , 9 , 10 ]. Owing to their excellent light-harvesting and photoemission properties combined with their amenable surface-functionalization to target specific cells, CPNs have been successfully applied as target-specific labels for both in vitro and in vivo fluorescence imaging and identification of cancer cells.…”

“…Despite the potentiality of these nanoparticles in cancer treatment, preclinical information regarding CPN pharmacokinetic, biodistribution, overall safety upon systemic application and particularly using GBM models in animals, is scarce [ 9 , 12 , 13 ]. To evaluate some of these parameters, in vivo imaging techniques, like fluorescence imaging and magnetic resonance imaging (MRI), can be highly informative.…”

Understanding the glioblastoma tumor biology to optimize photodynamic therapy: From molecular to cellular events

“…Unfailingly, these findings highlight the need to adapt the clinical use (PS and light doses and timing) of PDT when the goal is to promote an immune response and to identify the features for each PS. Figure 2) (Huang et al, 2015a;Ibarra et al, 2019Ibarra et al, , 2020. In another approach, immunosuppressive protumoral M2 macrophages became attractive targets in GBM management (Poon et al, 2017).…”

“…For instance, we recently demonstrated the potential of monocytes, circulating cell precursors of TAMs, to deliver CPN sensitizers into the GBM orthotopic model, and also to improve tumor penetration into GBM spheroids compared with non‐vectorized nanoparticles. In the latter case, the enhanced tumor penetration of CPN using the cell delivery led to a better PDT performance (Ibarra et al., 2020). Trojan horse cell delivery strategy to achieve target active accumulation of nanoparticles into GBM tumors was reported with different chemotherapeutic prodrugs (Pang et al., 2016; Wang et al., 2018) and photothermal nanoparticles (Baek et al., 2011; Hirschberg & Madsen, 2017; Madsen et al., 2013, 2015); but a few work reports have shown the potential of monocytes as stealth carriers of advances PSs for PDT treatment of GBM (Figure 2) (Huang et al, 2015a; Ibarra et al, 2019, 2020).…”