Linlin Li

In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.

Nanoformulations that can respond to the specific tumor microenvironment (TME), such as a weakly acidic pH, low oxygen, and high glutathione (GSH), show promise for killing cancer cells with minimal invasiveness and high specificity. In this study, we demonstrate self-assembled copper–amino acid mercaptide nanoparticles (Cu-Cys NPs) for in situ glutathione-activated and H2O2-reinforced chemodynamic therapy for drug-resistant breast cancer. After endocytosis into tumor cells, the Cu-Cys NPs could first react with local GSH, induce GSH depletion, and reduce Cu2+ to Cu+. Subsequently, the generated Cu+ would react with local H2O2 to generate toxic hydroxyl radicals (·OH) via a Fenton-like reaction, which has a fast reaction rate in the weakly acidic TME, that are responsible for tumor-cell apoptosis. Due to the high GSH and H2O2 concentration in tumor cells, which sequentially triggers the redox reactions, Cu-Cys NPs exhibited relatively high cytotoxicity to cancer cells, whereas normal cells were left alive. The in vivo results also proved that Cu-Cys NPs efficiently inhibited drug-resistant breast cancer without causing obvious systemic toxicity. As a novel copper mercaptide nanoformulation responsive to the TME, these Cu-Cys NPs may have great potential in chemodynamic cancer therapy.

In our previous study we reported that the interaction of nanoparticles with cells can be influenced by particle shape, but until now the effect of particle shape on in vivo behavior remained poorly understood. In the present study, we control the fabrication of fluorescent mesoporous silica nanoparticles (MSNs) by varying the concentration of reaction reagents especially to design a series of shapes. Two different shaped fluorescent MSNs (aspect ratios, 1.5, 5) were specially designed, and the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. Organ distributions show that intravenously administrated MSNs are mainly present in the liver, spleen and lung (>80%) and there is obvious particle shape effects on in vivo behaviors. Short-rod MSNs are easily trapped in the liver, while long-rod MSNs distribute in the spleen. MSNs with both aspect ratios have a higher content in the lung after PEG modification. We also found MSNs are mainly excreted by urine and feces, and the clearance rate of MSNs is primarily dependent on the particle shape, where short-rod MSNs have a more rapid clearance rate than long-rod MSNs in both excretion routes. Hematology, serum biochemistry, and histopathology results indicate that MSNs would not cause significant toxicity in vivo, but there is potential induction of biliary excretion and glomerular filtration dysfunction. These findings may provide useful information for the design of nanoscale delivery systems and the environmental fate of nanoparticles.

Recently, plasmonic copper sulfide (Cu2-xS) nanocrystals (NCs) have attracted much attention as materials for photothermal therapy (PTT). Previous reports have correlated photoinduced cell death to the photothermal heat mechanism of these NCs, and no evidence of their photodynamic properties has been reported yet. Herein we have prepared physiologically stable near-infrared (NIR) plasmonic copper sulfide NCs and analyzed their photothermal and photodynamic properties, including therapeutic potential in cultured melanoma cells and a murine melanoma model. Interestingly, we observe that, besides a high PTT efficacy, these copper sulfide NCs additionally possess intrinsic NIR induced photodynamic activity, whereupon they generate high levels of reactive oxygen species. Furthermore, in vitro and in vivo acute toxic responses of copper sulfide NCs were also elicited. This study highlights a mechanism of NIR light induced cancer therapy, which could pave the way toward more effective nanotherapeutics.

During natural tissue regeneration, tissue microenvironment and stem cell niche including cell-cell interaction, soluble factors, and extracellular matrix (ECM) provide a train of biochemical and biophysical cues for modulation of cell behaviors and tissue functions. Design of functional biomaterials to mimic the tissue/cell microenvironment have great potentials for tissue regeneration applications. Recently, electroactive biomaterials have drawn increasing attentions not only as scaffolds for cell adhesion and structural support, but also as modulators to regulate cell/tissue behaviors and function, especially for electrically excitable cells and tissues. More importantly, electrostimulation can further modulate a myriad of biological processes, from cell cycle, migration, proliferation and differentiation to neural conduction, muscle contraction, embryogenesis, and tissue regeneration. In this review, endogenous bioelectricity and piezoelectricity are introduced. Then, design rationale of electroactive biomaterials is discussed for imitating dynamic cell microenvironment, as well as their mediated electrostimulation and the applying pathways. Recent advances in electroactive biomaterials are systematically overviewed for modulation of stem cell fate and tissue regeneration, mainly including nerve regeneration, bone tissue engineering, and cardiac tissue engineering. Finally, the significance for simulating the native tissue microenvironment is emphasized and the open challenges and future perspectives of electroactive biomaterials are concluded.