A Pillar-layered Metal-organic Frameworks Based On BODIPY For Chemo-Photodynamic Therapy

Malignant tumors kill millions of people every year,and the treatment methods are attracting increasing attention.At present,chemotherapy and radiotherapy are playing the leading role in tumor treatment.However,monotherapy has been proven to be suboptimal due to its side effects and multiple drug resistance.Combination therapy of multiple treatments is considered to be an effective alternative strategy to overcome side effects and improve treatment efficiency.For example,the combination of chemotherapy and photodynamic therapy(PDT)could improve efficacy,reduce side effects and delay multiple drug resistance,which has been proven to be of great potential.PDT has been widely used as an alternative to cancer since it was first approved for the treatment of bladder cancer in 1993.Compared with other traditional cancer therapies(such as chemotherapy),the toxicity and aggressiveness of PDT is negligible.PDT treatment is only performed where the light reaches,so large-scale treatment could be avoided.In addition,PDT could cause an inflammatory immune response and expand the scope of anti-tumor immune monitoring.(1)In this paper,we have developed a new type of multi-functional three-dimensional nanoplatform,named BBP-MOFs,for the combination therapy of chemo-PDT therapy.The BBP-MOFs,a novel two-fold pillar-layered metal-organic frameworks(MOFs)material,using BODIPY-derivate bipyridine as linker and Photosensitizer(PS),was successfully synthesized.Because of its large pore volume,specific surface area and high PS loading rate,it could serve as a drug carrier and PDT agent simultaneously.In addition,doxorubicin(DOX)could be performed as a traditional anti-tumor drug to be loaded into BBP-MOFs,and used as a tracer to determine the site of action of BBP-MOFs in vivo and the situation of DOX release to achieve the effect of visual therapy.We did characterization of structure,morphology and physical and chemical properties for BBP-MOFs through single crystal x-ray diffraction,powder x-ray diffraction(PXRD),infrared spectroscopy,elemental analysis,BET,TGA and TEM.And the results showed that the BBP-MOFs had regular morphology,larger specific surface area and good thermal and water stability,which is potential to be a drug carrier.(2)Through the analysis of structure and solid fluorescence,we could make a conclusion that the reverse offset face-to-face stacking of BOD-Bipyridine molecules in the BBP-MOFs leaded to significant?-? overlapping.And it made the BBP-MOFs show significant red-shift in their photoluminescence spectra which could enhance singlet oxygen production,improving photodynamic efficacy.(3)The loading capacity of DOX into BBP-MOFs was determined by ultraviolet absorption curve.The results showed that BBP-MOFs exhibit a high drug loading content of 50.98 %.Meanwhile,it showed controlled drug release due to the two-fold penetration structure.Furthermore,BBP-MOFs exhibited excellent therapeutic efficiencies with negligible side effects,the inhibition ratio of tumor was as high as 86.9 %.Moreover,BBP-MOFs/DOX could generate high levels of singlet oxygen under 660 nm light irradiation.The obtained BBP-MOFs/DOX chemo-PDT therapy system possessed ideal biocompatibility,sustained drug release,effective chemo-PDT therapeutic efficacy and excellent fluorescence imaging capacity.Such a system integrating chemotherapy,PDT and visual therapy in a single platform by a simple and efficient strategy,aimed for facilitating new possibilities for multifunctional therapeutic systems.