Zhang Lin, Lu Kun, Cao Yu, Cui Lei, Li Xi, Guo Peipei, Fu Hai, Zhu Chen-Hui
School of Chemistry and Life Science, School of Chemical Engineering, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, PR China.
Advanced Light Source Lawrence Berkeley, National Laboratory Berkeley, CA 94720, USA.
Int J Biol Macromol. 2024 Dec;282(Pt 6):137381. doi: 10.1016/j.ijbiomac.2024.137381. Epub 2024 Nov 7.
Designing potential agents and constructing hydrophilic nano-hydrogel platforms for biomedical and pharmaceutical applications, especially for polyoxometalate-based metal-organic frameworks (PMOF), present both great desirability and significant challenges. A unique open porous Cu(I)-isopolymolybdate-based metal-organic framework (CCUT) has been self-assembled through ionothermal processes for in vivo synergistic anti-cancer therapy. The periodicity of Drugs@CCUT-1 (nano-crystals of CCUT after cation exchange and anti-cancer drugs upload) has been investigated by synchrotron wide-angle X-ray scattering, confirming the lattice structure unchanged. To mitigate toxicity, enhance stimuli-responsive drug delivery, hydrophilicity, and biocompatibility, an injectable dual-layer chitosan//alginate-based nano-hydrogel is developed to incorporate Drugs@CCUT-1. Potential interactions between the chitosan layer and the surface of CCUT-1 have been analyzed by Density Functional Theory (DFT). Furthermore, the nanoparticles Drugs@CCUT-1@Gel exhibit efficient type I photodynamic therapy (PDT) and chemodynamic therapy (CDT) within the bio-window, effectively eradicating tumors in deep tissue. CCUT-1 generates a substantial amount of reactive oxygen species (ROS), stimulating the Keap1-Nrf2 signaling pathway and resulting in the expression of phase II enzymes, typically HO-1. CCUT-1@Gel not only demonstrates high capacity for anti-cancer drug upload and release, but also exhibits strong synergistic CDT/PDT in vivo anti-tumor efficacy. Hence, CCUT-1@Gel represents a promising in vivo nano-platform for synergistic chemotherapy (CT)/CDT/PDT three-in-one anti-cancer approach.
设计用于生物医学和制药应用的潜在药剂并构建亲水性纳米水凝胶平台，尤其是基于多金属氧酸盐的金属有机框架（PMOF），既具有巨大的吸引力，也带来了重大挑战。一种独特的基于开放多孔Cu（I）-异钼酸盐的金属有机框架（CCUT）已通过离子热过程自组装用于体内协同抗癌治疗。通过同步加速器广角X射线散射研究了药物@CCUT-1（阳离子交换和抗癌药物负载后CCUT的纳米晶体）的周期性，证实晶格结构未变。为了减轻毒性、增强刺激响应性药物递送、亲水性和生物相容性，开发了一种可注射的双层壳聚糖//藻酸盐基纳米水凝胶来包裹药物@CCUT-1。通过密度泛函理论（DFT）分析了壳聚糖层与CCUT-1表面之间的潜在相互作用。此外，纳米颗粒药物@CCUT-1@凝胶在生物窗口内表现出高效的I型光动力疗法（PDT）和化学动力疗法（CDT），有效根除深部组织中的肿瘤。CCUT-1产生大量活性氧（ROS），刺激Keap1-Nrf2信号通路并导致II期酶（通常是HO-1）的表达。CCUT-1@凝胶不仅显示出高抗癌药物负载和释放能力，还在体内抗肿瘤功效中表现出强大的协同CDT/PDT。因此，CCUT-1@凝胶代表了一种有前途的体内纳米平台，用于协同化疗（CT）/CDT/PDT三合一抗癌方法。
