RESUMO
Morphological modulation in covalent organic frameworks (COFs) with particular emphasis on the correlation between structure and target applications in biomedical fields, is currently in its early stage of evolution. Herein, a multifunctional rattle-architecture imine-based COF with a mobile core of gold nanoparticles (Au NPs) and an outer polydopamine (PDA) shell, tailored for cancer treatment, has been developed to effectively integrate dual responsive release capabilities with the potential for multiple therapeutic applications. The engineered COF displays outstanding crystallinity, a suitable size and precisely controlled morphological characteristics. By leveraging COF and PDA attributes, the successful co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic docetaxel (DTX) within discrete compartments is achieved responsive to both pH and near-infrared triggers. Designed nanocarrier outperforms prior COFs with a superior 83.7% DOX loading capacity, thanks to its expansive internal space and porous shell. Taking advantage of the inclusion of Au core and the concurrent presence of COF and PDA outer shells, the nanocarrier exhibits a significant photothermal-conversion capability. The rattle-architecture double-shelled Au@RCOF@PDA were functionalized with poly(ethylene glycol)-folic acid (PEG-FA) to confer the system with active-targeting capability and enhanced biocompatibility. Through in vitro and in vivo evaluations, the designed system demonstrates an exceptional synergistic anti-tumor effect, along with favorable biosafety and histocompatibility. This study not only sheds light on the remarkable merits offered by regulating the morphology of COF-based systems in cancer therapy but also highlights the potential for synergistic therapeutic approaches in advancing cancer treatment strategies.
RESUMO
Engineering bulk covalent organic frameworks (COFs) to access specific morphological structures holds paramount significance in boosting their functions in cancer treatment; nevertheless, scant effort has been dedicated to exploring this realm. Herein, silica core-shell templates and multifunctional COF-based reticulated hollow nanospheres (HCOFs) are novelly designed as a versatile nanoplatform to investigate the simultaneous effect of dual-drug chemotherapy and photothermal ablation. Taking advantage of the distinct structural properties of the template, the resulting two-dimensional (2D) HCOF, featuring large internal voids and a peripheral interconnected mesoporous shell, presents intriguing benefits over its bulk counterparts for cancer treatment, including a well-defined morphology, an outstanding drug loading capability (99.6%) attributed to its ultrahigh surface area (2087 m2/g), great crystallinity, improved tumor accumulation, and an adjustable drug release profile. After being loaded with hydrophilic doxorubicin with a remarkable loading capacity, the obtained drug-loaded HCOFs were coated with gold nanoparticles (Au NPs) to confer them with three properties, including pore entrance blockage, active-targeting capability, and improved biocompatibility via secondary modification, besides high near infrared (NIR) absorption for efficient photothermal hyperthermia cancer suppression. The resultant structure was functionalized with mono-6-thio-ß-cyclodextrin (ß-CD) as a second pocket to load docetaxel as the hydrophobic anticancer agent (combination index = 0.33). The dual-drug-loaded HCOF displayed both pH- and near-infrared-responsive on-demand drug release. In vitro and in vivo evaluations unveiled the prominent synergistic performance of coloaded HCOF in cancer elimination upon NIR light irradiation. This work opens up a new avenue for exciting applications of structurally engineered HCOFs as hydrophobic/hydrophilic drug carriers as well as multimodal treatment agents.
