Self-assembled nanoparticles based on supramolecular-organic frameworks and temoporfin for an enhanced photodynamic therapy in vitro and in vivo

Abstract

Water-soluble three-dimensional supramolecular-organic frameworks (SOFs) and temoporfin (mTHPC) are discovered to form uniform self-assembly nanoparticles. These nanoparticles demonstrate an improved 1O2 generation efficiency due to a reduced aggregation-caused quenching effect....

Conjugating aldoxorubicin to supramolecular organic frameworks: polymeric prodrugs with enhanced therapeutic efficacy and safety

“…31 When the tetrahedral backbone is incorporated with 2-aminoethoxy groups at the ends of the appended 4-phenylpyridinium units, the resulting precursor T2 co-assembles with CB[8] (1 : 2) to afford supramolecular organic framework SOF-OC 2 N which was revealed to have good biocompatibility and water-solubility. 31,35 We thus further introduced thiol groups on the four side chains to construct SOF-p1 and SOF-p2 as polymeric precursors for maleimide–thiol conjugation of AlDox (Scheme 1). For the preparation of SOF-p1 , four cysteine groups were first introduced to the tetrahedral backbone to afford compound T1 .…”

“…31,32 Previously we found that SOFs can in situ load anticancer agents and overcome the multidrug resistance of tumour cells to realize intracellular drug delivery and efficacy enhancement through the EPR effect. [32][33][34][35] Because the tetrahedral components can be readily functionalized at the ends of the appended aromatic units, 36 we conjectured that SOFs might be developed as albumin surrogates to conjugate AlDox or other small-molecule anticancer agents to attain increased efficacy through efficient conjugation, intracellular delivery and stimuli-responsive release. Here we describe the preparation of two SOF-based prodrugs by attaching AlDox to the interior of their regular pores through the thiol-maleimide conjugation approach.…”

Supramolecular Organic Frameworks: Exploring Water-Soluble, Regular Nanopores for Biomedical Applications

“…Temoporfin is a neutral porphyrin PDA clinically used in the treatment of skin cancers (Chart ). We recently found that dSOF1a , b , h could also include this PDA . Their inclusion efficiencies were very close, indicating that the inclusion was also driven by hydrophobicity.…”

“…The tetrahedral backbone can be modified by introducing different substituents to afford T1b-h , which coassembled with CB[8] to give rise to similar supramolecular architectures dSOF1b – h (Scheme ). ,,− dSOF1g and dSOF1h formed by T1g or T1h displayed the highest water solubility of 8.0 mM, indicating that their hydrophilic groups could remarkably increase the water solubility of the frameworks. The maximum tolerated doses (MTDs) of Wistar rats for dSOF1a , dSOF1b , dSOF1g , and dSOF1h (three males and three females per group) were determined to be 17, 31, 49, and 77 mg/kg, respectively, which corresponded to values of 0.16, 0.30, 0.47, and 0.74 g for an adult of 60 kg weight by assuming a conversion coefficient of 6.25.…”

“…dSOF1a – h were prepared in boiling water at the highest concentration of the tetrahedral components ,,− ,− but could maintain their nanoscale sizes at the low concentration of 50 μM at room temperature, indicating that the peripheral substituents of the tetrahedral components did not affect the stability of the frameworks. Therefore, they could not only function as antidotes to neutralize the anticoagulation activity of residual heparins and alleviate the posttreatment phototoxicity of residual PDAs but also work well as nonequilibrium carriers, conducting in situ loading and the intracellular delivery of antitumor drugs and PDAs, ,,,, which has been ascribed to the so-called enhanced permeability and retention (EPR) effect . Apart from inclusion-based biomedical applications, dSOFs can also be conjugated with antitumor agents, forming new supramolecular prodrugs to attain enhanced efficacy .…”