Responsive nanoplatforms: Versatile design strategies for efficient cancer theranostics

In recent years, with close cooperation between different disciplines, more and more smart “all-in-one” theranostic nanoplatforms with stimulus-responsive capability have been designed for biomedical applications, attracting much attention around the world. In this context, the stimuli-responsive components play a decisive role in the design of theranostic nanoagents with in vivo spatiotemporal mode. In this review, we outline some typical design strategies of responsive nanoplatforms for efficient cancer therapy from both material and biological perspectives. From the materials point of view, researchers have designed the smart nanoplatforms by functionalized modifications or doping strategy combined with adjustable or variable skeleton structure to achieve promising biomedical applications. From the biological point of view, the constructed nanoplatforms targeting the different physiological factors that characterize specific diseases are hopeful to address the challenges posed by the pathological environment in a specifical and efficient way, in order to achieve an individualized therapy. Finally, we prospect the present limitations and future development of responsive smart biomaterials

Third-order optical nonlinearity of cadmium sulfide nanoparticles loaded in mesostructured silica materials

Cadmium sulfide nanoparticles have been successfully incorporated in three forms of CTABtemplated mesoporous silica materials: one is the mesoporous silica spheres suspended in ethanol solution, the other is the mesoporous silica spheres spin-coated on glass slide, and the third is the dip-coated mesoporous silica thin film. The mesostructures were characterized by XRD and TEM, respectively. Linear optical properties were investigated using UV-visible spectra, and the diameter of the incorporated CdS nanoparticles was measured to be around 3.1 nm. Z-scan technique manifested that these three composites exhibited distinct third-order optical nonlinearities due to the different preparation techniques. Reverse saturation absorption could be detected in the CdS-loaded mesoporous silica spheres suspended in solution, while those dispersed on glass slide presented saturation absorption. The difference in nonlinear absorption of the two mesoporous silica sphere samples could be attributed to defect-related transitions. On the contrary, the CdS-loaded mesoporous silica thin film showed self-defocusing behavior with no nonlinear absorption signals. Compared to that of the CdS nanoparticles with larger size previously reported, the intrinsic microscopic third-order nonlinear optical susceptibility of those incorporated in CTAB-templated mesoporous thin film was increased as predicted by the quantum theory, and the third-order optical nonlinearity was further determined to arise from intraband transitions induced by quantum confinement. Copyrigh

Ca & Mn dual-ion hybrid nanostimulator boosting anti-tumor immunity via ferroptosis and innate immunity awakening

Limited by low tumor immunogenicity and the immunosuppressive tumor microenvironment (TME), triple-negative breast cancer (TNBC) has been poorly responsive to immunotherapy so far. Herein, a Ca & Mn dual-ion hybrid nanostimulator (CMS) is constructed to enhance anti-tumor immunity through ferroptosis inducing and innate immunity awakening, which can serve as a ferroptosis inducer and immunoadjuvant for TNBC concurrently. On one hand, glutathione (GSH) depletion and reactive oxygen species (ROS) generation can be achieved due to the mixed valence state of Mn in CMS. On the other hand, as an exotic Ca2+ supplier, CMS causes mitochondrial Ca2+ overload, which further amplifies the oxidative stress. Significantly, tumor cells undergo ferroptosis because of the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxidation (LPO). More impressively, CMS can act as an immunoadjuvant to awaken innate immunity by alleviating intra-tumor hypoxia and Mn2+-induced activation of the STING signaling pathway, which promotes polarization of tumor-associated macrophages (TAMs) and activation of dendritic cells (DCs) for antigen presentation and subsequent infiltration of tumor-specific cytotoxic T lymphocytes (CTLs) into tumor tissues. Taken together, this work demonstrates a novel strategy of simultaneously inducing ferroptosis and awakening innate immunity, offering a new perspective for effective tumor immunotherapy of TNBC

Break-up of two-dimensional MnO2 nanosheets promotes ultrasensitive ph-triggered theranostics of cancer

A study was conducted to demonstrate how MnO nanosheets promoted ultrasensitive pH-triggered theranostics of cancer. It was demonstrated that the break-up of drug-loaded MnO nanosheets in a mild acidic environment could release the loaded cargos for internally pH-triggered drug release. The released Mn(II) ions from the continuous break-up and disintegration of MnO nanosheets could be easily metabolized by the kidneys, which allowed circumvention of the intractable degradation issue of traditional inorganic nanosystems, such as well-known silica, gold, and carbon-based nanomaterials. The synthesis of exfoliated MnO nanosheets was conducted according to a reported process with some modifications

Biocompatibility, MR imaging and targeted drug delivery of a rattle-type magnetic mesoporous silica nanosphere system conjugated with PEG and cancer-cell-specific ligands

Rattle-type magnetic mesoporous silica nanospheres (RMMSNs) with a magnetic core and a mesoporous silica shell were prepared, and then the surface properties of the nanospheres were modified with biocompatible polymer poly(ethylene glycol) (PEG) and cancer-cell-specific ligand folic acid (FA), with the aim of specifically targeting cancer cells. Combined Prussian blue staining, magnetic resonance imaging, and high-resolution sector field inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis revealed that the obtained RMMSN-PEG/FA nanocomposite can specifically target cancer cells over-expressing FA receptors (FRs). The nanocomposites displayed very low in vitro toxicity and negligible hemolytic activity, which is in favor of further biological applications. Water-insoluble anticancer drug docetaxel was loaded into the surface-modified RMMSNs and delivered into human cancer cells via cell uptake. Surface conjugation with cancer-specific targeting agent FA increased the uptake into cancer cells that over-express FRs. In addition, after intravenous injection, the RMMSN-PEG/FA nanocomposite could be transported to the designated organs under an external magnetic field. Findings from this study suggest that the RMMSN-PEG/FA could be used as a platform for simultaneous imaging and therapeutic applications