Microfluidized Dextran Microgels Loaded with Cisplatin/SPION Lipid Nanotherapeutics for Local Colon Cancer Treatment via Oral Administration.

Multifunctional sequential targeted delivery system is developed as an efficient therapeutic strategy against malignant tumors with selective accumulation and minimal systemic drug absorption. The therapeutic system is comprised of microfluidized dextran microgels encapsulating cisplatin/superparamagnetic iron oxide nanoparticles (SPIONs)-loaded trilaurin-based lipid nanoparticles (LNPs). The microgel system is imparted hierarchically dual targeting via dextran and folic acid (FA) residues, leading to increases both in retention of the microgels in colon and in cellular uptake of the therapeutic LNPs by colon cancer cells while being used for oral therapeutic delivery. Encapsulation of the therapeutic LNPs into dextran microgels attained by microfluidized crosslinking reaction reduces gastrointestinal adhesion and prevents the FA-modified LNPs from cellular transport by proton-coupled FA transporters in small intestine during their oral delivery to colon. Upon enzymatic degradation of the dextran microgels by dextranase present exclusively in colon, LNPs thus released become more recognizable and readily internalized by FA receptor-overexpressing colon cancer cells. The combined chemo/magnetothermal therapeutic effect of dual targeted lipid nanoparticle-loaded microgels from entrapped lipidized cisplatin and alternating magnetic field-treated SPIONs significantly inhibits tumor growth and suppresses metastatic peritoneal carcinomatosis in orthotopic colon cancer-bearing mice.

Bis(2,6-dihy-droxy-benzoato-κO,O)(nitrato-κO,O')bis-(1,10-phenanthroline-κN,N')praseodymium(III).

The mononuclear title complex, [Pr(C(7)H(5)O(3))(2)(NO(3))(C(12)H(8)N(2))(2)], is isostructural with related complexes of other lanthanides. The Pr(III) atom is in a pseudo-bicapped square-anti-prismatic geometry, formed by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and six O atoms, four from two 2,6-dihy-droxy-benzoate (DHB) ligands and the other two from nitrate anions. π-π stacking inter-actions between the phen and DHB ligands [centroid-centroid distances = 3.518 (2) and 3.778 (2) Å] and the phen and phen ligands [face-to-face separation = 3.427 (6) Å] of adjacent complexes stabilize the crystal structure. Intra-molecular O-H⋯O hydrogen bonds are observed in the DHB ligands.

Bis(2,6-dihy-droxy-benzoato-κO,O)(nitrato-κO,O')bis-(1,10-phenanthroline-κN,N')cerium(III).

The mononuclear title complex, [Ce(C(7)H(5)O(3))(2)(NO(3))(C(12)H(8)N(2))(2)], is isostructural to other related lanthanide structures. The Ce atom is in a pseudo-bicapped square-anti-prismatic geometry formed by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and by six O atoms, four from two 2,6-dihy-droxy-benzoate (DHB) ligands and the other two from a nitrate anion. π-π stacking inter-actions between phen and DHB ligands [centroid-centroid distances = 3.513 (3) and 3.762 (2) Å] and phen and phen ligands [face-to-face separation = 3.423 (7) Å] of adjacent complexes stabilize the crystal structure. Intra-molecular O-H⋯O hydrogen bonds are observed in the DHB ligands.

Bis(2,6-dihy-droxy-benzoato-κO,O)(nitrato-κO,O')bis-(1,10-phenanthroline-κN,N')samarium(III).

The title mononuclear complex, [Sm(C(7)H(5)O(3))(2)(NO(3))(C(12)H(8)N(2))(2)], is isostructural with that of other lanthanides. The Sm atom is in a pseudo-bicapped square-anti-prismatic geometry, formed by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and by six O atoms, four from two 2,6-dihy-droxy-benzoate (DHB) ligands and the other two from a nitrate anion. π-π stacking inter-actions between phen and DHB ligands [centroid-centroid distance = 3.528 (4) and 3.812 (3) Å], and phen and phen ligands [face-to-face separation = 3.420 (10) Å] of adjacent complexes stabilize the crystal structure. Intra-molecular O-H⋯O hydrogen bonds are observed in the DHB ligands.