Abstract
Mesoporous silica nanoparticles (MSNs) have emerged as a prominent nanomedicine platform, especially for tumor-related nanocarrier systems. However, there is increasing concern about the ability of nanoparticles (NPs) to penetrate solid tumors, resulting in compromised antitumor efficacy. Because the physicochemical properties of NPs play a significant role in their penetration and accumulation in solid tumors, it is essential to systematically study their relationship in a model system. Here, we report a multihierarchical assessment of the accumulation and penetration of fluorescence-labeled MSNs with nine different physicochemical properties in tumor spheroids using two-photon microscopy. Our results indicated that individual physicochemical parameters separately could not define the MSNs’ ability to accumulate in a deeper tumor region; their features are entangled. We observed that the MSNs’ stability determined their success in reaching the hypoxia region. Moreover, the change in the MSNs’ penetration behavior postprotein crowning was associated with both the original properties of NPs and proteins on their surfaces.
Highlights
Tumor-targeting nanoparticle (NP) drug delivery systems have been proven to be promising in advanced anticancer treatment because the anticancer drugs can be delivered to the tumor sites reducing the side effects and toxicity to the healthy cells [1]
To study the penetration of Mesoporous silica nanoparticles (MSNs) in spheroids in the absence of serum, the spheroid in 96-well plates was treated under a serum starvation medium for 30 min at 37 ◦ C
rhodamine B isothiocyanate (RITC)-labeled MSNs in a free serum medium at 500 μg/mL concentration in a final 100 μL volume were incubated with the spheroid for 16 h at 37 ◦ C
Summary
Tumor-targeting nanoparticle (NP) drug delivery systems have been proven to be promising in advanced anticancer treatment because the anticancer drugs can be delivered to the tumor sites reducing the side effects and toxicity to the healthy cells [1]. Despite these exciting results for NPs as anticancer drug nanocarriers, their efficacy is still limited; only a few of them meet clinical expectations [2]. One of the most promising NPs in the tumor-targeting delivery system is the mesoporous silica nanoparticle (MSN), which possesses many desirable properties for nanocarriers such as tunability of size and surface functionality, controllable property, biocompatibility and facile surface modification [7,8,9,10,11,12]
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