Stiffness-Transformable Nanoplatforms Responsive to the Tumor Microenvironment for Enhanced Tumor Therapeutic Efficacy

Herein, we report, for the first time, a unique stiffness-transformable manganese oxide hybridized mesoporous organosilica nanoplatform (MMON) for enhancing tumor therapeutic efficacy. The prepared MMONs had a quasi-spherical morphology and were completely transformed into soft bowl-like nanocapsules in the simulated tumor microenvironment through the breakage of Mn−O bonds, which decreased their Young's modulus from 165.7 to 84.5 MPa. Due to their unique stiffness transformation properties, the MMONs had reduced macrophage internalization, improved tumor cell uptake, and enhanced penetration of multicellular spheroids. In addition, in vivo experiments showed that the MMONs displayed a 3.79- and 2.90-fold decrease in non-specific liver distribution and a 2.87- and 1.83-fold increase in tumor accumulation compared to their soft and stiff counterparts, respectively. Furthermore, chlorin e6 (Ce6) modified MMONs had significantly improved photodynamic therapeutic effect.     

纳米粒子/聚合物复合光热平台的构筑和应用

叙述了一系列增强纳米粒子光热性能的方法,包括通过自组装方法调控纳米粒子的空间排列,进而优化电子结构和光热转化性能;在纳米粒子及其组装结构外表面进一步包覆具有光热性质的聚合物等.这些手段能够有效地增强光热试剂在近红外光区的消光能力,达到增强光热性能的目的.另外,包覆聚合物壳层后,纳米粒子的胶体稳定性、光稳定性以及生物兼容性都能得到进一步提高,为后续的体外细胞实验和动物体内肿瘤模型实验提供了可能.     

A pH-response multifunctional nanoplatform based on NaGdF4:Yb,Er,Fe@Ce6@mSiO2-DOX for synergistic photodynamic/chemotherapy of cancer cells

Cancer is one of the major diseases that seriously threaten human health. Drug delivery nanoplatforms for tumor treatment have attracted increasing attention owing to their unique advantages such as good specificity and few side effects. This study aimed to fabricate a pH-responsive drug release multifunctional nanoplatform NaGdF₄:Yb,Er,Fe@Ce6@mSiO₂-DOX. In the platform, Fe³⁺ doping enhanced the fluorescence intensity of NaGdF₄:Yb, Er by 5.8 folds, and the mSiO₂ shell substantially increased the specific surface area of nanomaterials (559.257 m²/g). The loading rates of chlorin e6 and doxorubicin hydrochloride (DOX) on NaGdF₄:Yb,Er,Fe@Ce6@mSiO₂-DOX reached 28.58 ± 0.85% and 87.53 ± 5.53%, respectively. Additionally, the DOX release rate from the nanoplatform was only 24.4% after 72 h at pH 7.4. However, under tumor microenvironment conditions (pH 5.0), the release rate of DOX increased to 85.3% after 72 h. The nanoplatform could generate reactive oxygen species (ROS) under 980 nm near-infrared excitation. Moreover, the nanoplatform exhibited a strong comprehensive killing efficiency against cancer cells. The viabilities of HeLa, MCF-7, and HepG2 cancer cells were only 18.5, 11.4, and 9.3%, respectively, after being treated with a combination of photodynamic therapy and chemotherapy. The constructed nanoplatform exhibits great application potential in cancer treatment.     

Synergy of light-controlled Pd nanozymes with NO therapy for biofilm elimination and diabetic wound treatment acceleration

The presence of bacteria, existing as highly organized biofilm communities, in chronic non-healing wounds has been identified as a significant impediment for wound healing. Nanozymes, with unique antimicrobial mechanisms, as a new alternative for antibiotics, have the potential to synergize with nitric oxide (NO) with enhanced antibacterial and antibiofilm ability. However, the always-on state of nanozymes and the reactivity of NO limit their clinical applications. In this context, an intelligent and multifunctional Pd-MOF@PAzo@SNP nanoplatform was fabricated using UiO-66 as a palladium (Pd) nanozyme-loading vehicle, then a surface modification with photosensitive polyazobenzene (PAzo), and the adsorption of the NO donor sodium nitroprusside (SNP) via a host-guest interaction between β-cyclodextrin-modified hyaluronic acid (β-CD-HA) and azobenzene. The activity of Pd-nanozyme was easily controlled via ultraviolet (UV) light, and its photosensitivity was regulated by changing the side-chain unit length of PAzo. Furthermore, NO was released in response to the UV irradiation and played a synergistic role with the peroxidase activity of Pd nanozyme, exhibiting excellent antibacterial and antibiofilm activity in the presence of 0.01 mM hydrogen peroxide (H₂O₂). In vivo, Pd-MOF@PAzo@SNP accelerated the healing of a biofilm-infected diabetic wound by dispersing the biofilm, reducing bacterial burden, and promoting angiogenesis and collagen deposition. Overall, the nanoplatform provides a reliable and highly efficient strategy to develop an intelligent nanozyme synergy with NO therapy in chronic wound management.