Mesenchymal Stem Cells Aggregate and Deliver Gold Nanoparticles to Tumors for Photothermal Therapy

Abstract

Gold nanoparticles (AuNPs) have been extensively studied for photothermal cancer therapy because AuNPs can generate heat upon near-infrared irradiation. However, improving their tumor-targeting efficiency and optimizing the nanoparticle size for maximizing the photothermal effect remain challenging. We demonstrate that mesenchymal stem cells (MSCs) can aggregate pH-sensitive gold nanoparticles (PSAuNPs) in mildly acidic endosomes, target tumors, and be used for photothermal therapy. These aggregated structures had a higher cellular retention in comparison to pH-insensitive, control AuNPs (cAuNPs), which is important for the cell-based delivery process. PSAuNP-laden MSCs (MSC-PSAuNPs) injected intravenously to tumor-bearing mice show a 37-fold higher tumor-targeting efficiency (5.6% of the injected dose) and 8.3 °C higher heat generation compared to injections of cAuNPs after irradiation, which results in a significantly enhanced anticancer effect.

Tumor-tropic endothelial colony forming cells (ECFCs) loaded with near-infrared sensitive Au nanoparticles: A “cellular stove” approach to the photoablation of melanoma

“…Noticeably, the MHR of the enriched cells, typically 1400°C s −1 M −1 , is roughly 7-fold that of ChAumix in colloidal solution. This result is in agreement with the observation that closely packed nanoparticles behaves as improved heat generators [28], which can also explain the good heating performances found by Kang et alii [29], obtained by aggregating spherical nanoparticles via pH-induced modification of the nanoparticles surface electrical charge. In that case, from the data presented, a cellular MHR of 1190°C s −1 M −1 can be inferred, quite close to the MHR calculated for ECFCs.…”

“…As a final remark, if from one side the presence of broadly dispersed ChAumix limits the absorption at a given excitation wavelength to a restricted number of tuned particles, on the other side the absorbance remains higher than the 90% of the maximum value in a wide band (~ 100 nm), and thus may comply more easily with laser users, hopefully in hospital. We measured Au loadings as high as 220 pg/cell, a cell enrichment that, at our knowledge, has not been reached so far [2, 29, 32]. This is due to the high efficiency of the enriching process, likely driven by the attractive forces between positively charged Au nanoparticles and negatively charged cells membranes in agreement with the observations reported by M. Pérez-Hernández [35].…”

“…Use of cells with tumor-homing capacity for delivery of nanomedicines is a relatively new and appealing approach in cancer therapy. In a recent study, Kang and coworkers [29] demonstrated that harnessing of MSCs as delivery vehicles of gold nanospheres led to 4-fold increase in tumor accumulation compared with intravenous injection of free nanoparticles. Although these results are promising, the biodistribution study still showed a low efficacy of tumor targeting after intravenous administration and hence the need to reduce their off-target accumulation and improve tumor tropic features.…”

A Light‐Triggered Mesenchymal Stem Cell Delivery System for Photoacoustic Imaging and Chemo‐Photothermal Therapy of Triple Negative Breast Cancer

“…Hypoxic‐treated neural stem cells showed the overexpression of CXCR4 and could enhance the tumor migration ability 23. There were numerous studies utilized the homing ability of stem cells for tumor targeting 24, 25, 26, 27, 28. In addition, it has been reported that iron oxide nanoparticles with the released iron ions could increase the CXCR4 expression on the mesenchymal stem cell (MSC) surface and promote the migration ability 29.…”

Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities

“…This therapeutic approach is extremely promising and for this reason is under extensive preclinical and clinical investigations for the treatment of various medical conditions, including cancer. 19,20 The current understanding of the relationship between optical properties of the NIR-emitting NPs, NP heating efficiency, and their applicative potential in the medical field as theranostic probes is limited. In this context, in the present study, we evaluated both the PA and fluorescence capabilities of dye-doped NIR-pluronic-silica NPs (NIR-PluS NPs), which display a tunable intensity profile across the NIR spectrum.…”