Development of a Soft-templating Method for the Synthesis of Nanoscale Metal-organic Framework (NMOF) Nanocomposites and Their Application in Combinatorial Cancer Therapy

Project: Research

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Description

Metal-organic frameworks (MOFs) have shown desirable properties for biomedicalapplications. For example, due to their high drug loading capacity and potentialbiodegradability, nanoscale MOFs (NMOFs) have been recognized as a promising vectorfor drug delivery. However, there are still a number of challenges in the advance ofNMOFs technology for drug delivery. In particular, size controllability in nanoscalerange, morphology uniformity, and surface modifiability of NMOFs are major issues tobe concerned, because these factors have significant influence on the cellular uptake, invivo stability, drug delivery efficacy, and targetability. To solve the problems, we recentlysynthesized zeolitic imidazolate framework-8 (ZIF-8) NMOF nanocomposites byemploying poly(acrylic acid) PAA nanospheres as a soft template. This approach enabledus to have an effective control on the size of NMOF nanocomposites by employing PAAtemplates with different sizes; meanwhile flexible surface modification could beachieved by conjugating various functional groups to the PAA templates terminated with–COOH. Beyond these, we revealed that these ZIF-8 NMOF nanocomposites possessedover 45wt% doxorubicin (DOX) loading capacity, which is significantly higher thancommonly used nanocarriers.Based on these encouraging preliminary results, we propose in this project to establish asoft-templating approach to synthesize a range of NMOF nanocomposites withcontrolled size and surface characteristics, and understand factors that influence theNMOFs growth on soft templates. Considering that the metal ions, organic linkers, andreaction conditions strongly influence the morphology, particle/pore size, stability anddrug delivery performance, we will produce NMOF nanocomposites comprising differentmetal ions (e.g., Zn and Fe) and organic ligands (e.g., 2-methylimidazole, muconic acid,and amino terephthalic) and systematically study their impacts on the properties of theproduced nanocomposites. Furthermore, as an example application, the prepared NMOFnanocomposites will be co-loaded with photosensitizers and chemotherapeutic drugs –photosensitizers conjugated to the PAA templates and anticancer drug DOX loaded toNMOFs by physical absorption. In vitro and in vivo tests will be conducted to evaluatetheir combinatorial photodynamic and chemotherapy performance and safety profiles.The success of this project will form a guideline for designing and fabricating newNMOF nanocomposites, and make this novel material promising for not only cancertreatment, but also for other applications such as air purification, catalysis, electronicsand gas storage/separation.

Detail(s)

Project number9042561
Grant typeGRF
StatusFinished
Effective start/end date1/07/1710/12/21