Soft Mesoporous Organosilica Nanoplatforms Improve Blood Circulation, Tumor Accumulation/Penetration, and Photodynamic Efficacy

Abstract

To date, the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration. Herein, a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared, denoted SMONs-HA-Cy5.5, and comparative studies between SMONs-HA-Cy5.5 (24.2 MPa) and stiff counterparts (79.2 MPa) are conducted. Results indicate that, apart from exhibiting a twofold increase in tumor cellular uptake, the soft nanoplatforms also display a remarkable pharmacokinetic advantage, resulting in considerably improved tumor accumulation. Moreover, SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration, achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts. Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels, diffuse farther in the dense extracellular matrix, and reach deeper tumor tissues compared to the stiff ones. Specifically, the soft nanoplatforms generate a 16-fold improvement (43 vs. 2.72 μm) in diffusion distance in tumor parenchyma. Based on the significantly improved blood circulation and tumor accumulation/penetration, a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5. The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.

Elastic Nanovaccine Enhances Dendritic Cell‐Mediated Tumor Immunotherapy

“…The high-efficiency transportation to LNs is supported by our previous finding that SMON nanoplatforms have remarkable tissue penetration. [39] Based on these results, SMONV promotes antigen delivery into draining LNs, which maximizes antigen exposure in the lymphatic system and enhances DC-mediated T-cell immune responses.…”

“…The mechanism of SMON obtained by preferential etching of MON has been reported in our previous work. [38,39] Briefly, MON, which is synthesized using a CTABdirected sol-gel process, has a more stable outer layer because the Si-OH group on its surface is highly cross-linked by ammonia catalysis. When MON is dispersed in a NaOH solution, the less condensed cores and the inorganic silica species in the shell are preferentially etched by OH − , leading to a significant increase in the proportion of flexible Si-R-Si chains and noncross-linked free Si-OX groups in the overall framework.…”

“…The ability of SMONV to be quickly and efficiently internalized by DCs can be explained by the fact that the elasticity and deformability of soft NPs can reduce the invagination of the cell membrane, thus saving the corresponding energy required for wrapping NPs in the process of internalization. [38,39] After cellular internalization, antigens are generally confined to intracellular compartments in the absence of endosomal escape; as such, antigens undergo lysosomal degradation. [47] However, major cross-presentation occurs through the cytosolic exportation of exogenous antigens from endosomal vesicles, followed by proteasomal degradation, transport to the endoplasmic reticulum, and loading on MHC I molecules.…”

“…[37] Recently, NP elasticity has been proven to play a pivotal role in the nanobiological interfaces, such as cellular uptake, [38][39][40][41] circulation, [39,42] and tissue accumulation. [39,43] However, researchers still have not determined whether the elastic properties of NPs affect the tumor vaccination cascade and the immunotherapeutic efficacy of NBI.…”

Tuning Nanosiliceous Framework for Enhanced Cancer Theranostic Applications

“…fabricated hollow soft shell MONs by selectively etching a portion of the silica from the thioether hybridized framework. [ 124 ] The obtained soft MONs with hyaluronic acid as surface ligands had a hollowed structure and wrinkled morphology, featuring a much lower Young's modulus (24.2 MPa) than their rigid counterparts (79.2 MPa). The in vitro results indicated that the soft MONs had increased cellular uptake and deeper tumor penetration depth in 3D tumor spheroids of MCF‐7 cancer cells.…”