A multifunctional metal–organic framework based tumor targeting drug delivery system for cancer therapy

Abstract

Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free "green" post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.

Benzoic‐Imine‐Based Physiological‐pH‐Responsive Materials for Biomedical Applications

“…[89] Besides pH sensitivity,a dditional stimuli groups, such as the redox-responsive disulfide bond, are frequently introduced into drug-delivery systems to furthert rigger the drug release, for example, by using the intracellular reducing environment in cancercells. [90,91] Recently,disulfide and benzoic imine bonds have been selectively capped at the two corresponding ends of at umor-targeting peptide, RGDFFFFC. Mesoporouss ilica nanoparticles were treated with the modified peptide, followed by af urtherc onnection with poly(ethylene glycol).…”

Lymphatic targeting drug delivery system and tumor treatment

“…The process of metastasis and proliferation of malignant cells is the process of transferring cells to lymph nodes. Therefore, if the lymphatic targeting drug delivery can be conducted, the drugs will directly act on the metastasis, so that the control rate of malignant tumors can be increased [12][13][14][15] . Lymph is lipophilic, and treating the patients with malignant tumors with liposome or niosome drugs is the main idea of the current lymphatic targeting drug delivery.…”

Nanoparticles of Metal‐Organic Frameworks: On the Road to In Vivo Efficacy in Biomedicine

“…Numerous strategies have been proposed so far to modify the surface of nanoMOFs using a large variety of molecules, such as nucleic acids, polymers, cyclodextrins (CDs), or lipids, resulting into various degrees of improvement of the particles properties. One can classify these approaches into three categories: covalent, noncovalent, ( Table 2 ) or core–shell, as detailed below.…”

“…A more sophisticated system was developed by Wang et al who prepared surface modified by the mesoporous iron(III) amino‐benzenedicarboxylate MIL‐101(Fe) NPs loaded with Dox. After the synthesis of the NPs, to avoid premature drug release through systemic circulation, CD and PEG chains were added by a one‐pot, and organic solvent‐free “green” postsynthetic procedure based on click chemistry and host–guest interactions forming PEG‐RGD‐β‐CD‐SS‐MIL‐101(Fe) NPs . This led to a better stability in PBS and prevented from fast degradation compared to uncoated particles.…”