Softness-Aided Mild Hyperthermia Boosts Stiff Nanomedicine by Regulating Tumor Mechanics.

Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild-hyperthermia photothermal therapy (mild-PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)-loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild-PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)-loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness-mediated mild-PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

Nanopatterning of beaded poly(lactic acid) nanofibers for highly electroactive, breathable, UV-shielding and antibacterial protective membranes.

Despite great potential in fabrication of biodegradable protective membranes by electrospinning of poly(lactic acid) (PLA) nanofibers, it is still thwarted by smooth surfaces and poor electroactivity that challenge the promotion of electret properties and long-term air filtration performance. Here, a microwave-assisted synthetic method was used to customize dielectric TiO2 nanocrystals of ultrasmall and uniform dimensions (∼30 nm), which were homogeneously embedded at beaded PLA nanofibers (PLA@TiO2, diameter of around 280 nm) by the combined "electrospinning-electrospray" approach. With small amounts of TiO2 (2, 4 and 6 wt%), the nanopatterned PLA@TiO2 nanofibrous membranes (NFMs) were characterized by largely increased dielectric constants (nearly 1.9), surface potential (up to 1.63 kV) and triboelectric properties (output voltage of 12.2 V). Arising from the improved electroactivity and self-charging mechanisms, the nanopatterned PLA@TiO2 NFMs exhibited remarkable PM0.3 filtration properties (97.9 %, 254.6 Pa) even at the highest airflow rate of 85 L/min, surpassing those of pure PLA membranes (86.2 %, 483.7 Pa). This was moreover accompanied by inhibition rates of 100 % against both E. coli and S. aureus, as well as excellent UV-blocking properties (UPF as high as 3.8, TUVA of 50.9 % and TUVB of 20.1 %). The breathable and electroactive nanopatterned PLA NFMs permit promising applications in multifunctional protective membranes toward excellent UV shielding and high-efficiency removal of both PMs and pathogens.

Mechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels.

Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.

Preparation and characterization of a titanium bonding porcelain.

The titanium bonding porcelain was synthesized through normal melting-derived route using borate-silicate system. The porcelain was characterized by thermal expansion, X-ray diffraction, scanning electron microscope and cytotoxicity tests. The results of X-ray diffraction showed that the main phase of the bonding porcelain was SnO2. The SnO2 microcrystals precipitated from the glass matrix when the SnO2 content was increased. The thermal expansion coefficient of bonding porcelains decreased with the increasing concentration of SiO2. The thermal expansion coefficient of bonding porcelains first decreased slightly with the increasing of B2O3 concentration (from 0 wt% to 10 wt%) and then increased to about 9.4×10(-6)/°C(from 10 wt% to 12 wt%). As an intermediate, B2O3 can act as both network formers and modifiers, depending on the relationship between the concentration of basic oxides and intermediates. The Vickers hardness of bonding porcelains increased with the increase of SnO2 concentration. When SnO2 concentration was 6 wt%, only Si and Sn elements attended the reaction between titanium and porcelain and mainly adhesive fracture was found at Ti-porcelain interface. When SnO2 concentration was 12 wt%, failure of the titanium-porcelain predominantly occurred in the bonding porcelain and mainly cohesive fracture was found at Ti-porcelain interface. The methyl thiazolyl tetrazolium assay results demonstrated that the cytotoxicity of the titanium porcelain was ranked as 0.