Hitchhiking Nanoparticles: Mesenchymal Stem Cell-Mediated Delivery of Theranostic Nanoparticles

Abstract

Nanotechnology has emerged as a promising solution to permanent elimination of cancer. However, nanoparticles themselves lack specificity to tumors. Due to enhanced migration to tumors, mesenchymal stem cells (MSCs) were suggested as cell-mediated delivery vehicles of nanoparticles. In this study, we have constructed a complex composed of photoluminescent quantum dots (QDs) and a photosensitizer chlorin e6 (Ce6) to obtain multifunctional nanoparticles, combining cancer diagnostic and therapeutic properties. QDs serve as energy donorsexcited QDs transfer energy to the attached Ce6 via Forster resonance energy transfer, which in turn generates reactive oxygen species. Here, the physicochemical properties of the QD-Ce6 complex and singlet oxygen generation were measured, and the stability in protein-rich media was evaluated, showing that the complex remains the most stable in proteinfree medium. In vitro studies on MSC and cancer cell response to the QD-Ce6 complex revealed the complex-loaded MSCs' potential to transport theranostic nanoparticles and induce cancer cell death. In vivo studies proved the therapeutic efficacy, as the survival of tumor-bearing mice was statistically significantly increased, while tumor progression and metastases were slowed down.

The Role of Hitchhiking in Cancer Therapeutics—A Review

“…Moreover, it is hypothesized that B cells, [19,30] dendritic cells, [19,30] natural killer cells, [19,44] and platelets [19,45,46] could be a potential source for cell-mediated hitchhiking strategies. Recently, Dapkute et al [47] demonstrated the use of mesenchymal stem cell-driven nanosystems for treating tumors because of their improved migration to the pathological site. This section of the review discusses the application of chemotherapeutic cargo hitchhiked circulatory cells for tumor targeting and treatment.…”

“…MSCs relocate to regions of tissue injury and inflammation, such as tumors. [19,47] A new category of contrast mediators was based on gold nanocages for in vitro and in vivo surveillance of human MSCs utilizing two-photon imaging and photoacoustic microscopy. [105] Hitchhiking-mediated delivery of fluorescent magnetic nanoparticles (FMNPs) to tumors is an approach utilizing MSCs.…”

“…Altogether, modified MSCs can be used to deliver strong immunostimulatory substances to remote areas of inflammation through a "hit-and-run" tactic. [107] An MSC-driven novel tumor theranostic complex has been developed by Dapkute et al [47] They raised the feasibility of MSCdriven theranostic nanoparticles administration. To prepare multifaceted nanoparticles, they produced a combination of photoluminescent quantum dots (PQDs) and the PS chlorin e6 (Ce6).…”

“…An MSC‐driven novel tumor theranostic complex has been developed by Dapkute et al. [ 47 ] They raised the feasibility of MSC‐driven theranostic nanoparticles administration. To prepare multifaceted nanoparticles, they produced a combination of photoluminescent quantum dots (PQDs) and the PS chlorin e6 (Ce6).…”

“…In vivo investigations confirmed the treatment efficacy, with tumor‐bearing mice surviving longer and diminished tumor development and metastasis. [ 47 ]…”