ZIF-90 nanoparticles modified with a homing peptide for targeted delivery of cisplatin

Abstract

To improve the selective delivery of cisplatin (Cis) to cancer cells, we report and establish the significance of active, targeting drug delivery nanosystems for efficient treatment of lung cancer. Specifically, pH-responsive nano-sized zeolitic imidazolate framework (nZIF-90) was synthesized, post-synthetically modified with an Arg-Gly-Asp peptide motif (RGD@nZIF-90), a known cancer cell homing peptide, and loaded with a large amount of Cis (RGD@Cis⊂nZIF-90). RGD@Cis⊂nZIF-90 was shown to be highly stable under physiological conditions (pH = 7.4) with framework dissociation occurring under slightly acidic conditions (pH = 5.0)–conditions relevant to tumor cells–from which 90% of the encapsulated Cis was released in a sustained manner. In vitro assays demonstrated that RGD@Cis⊂nZIF-90 achieved significantly better cytotoxicity (65% at 6.25 μg ml−1) and selectivity (selectivity index = 4.18 after 48 h of treatment) against adenocarcinoma alveolar epithelial cancer cells (A549) when compared with the unmodified Cis⊂nZIF-90 (22%). Cellular uptake using A549 cells indicated that RGD@Cis⊂nZIF-90 was rapidly internalized leading to significant cell death. After successfully realizing this nanocarrier system, we demonstrated its efficacy in transporting and delivering Cis to cancer cells.

pH-Responsive Graphene Oxide-Based 2D/3D Composite for Enhancing Anti-Corrosion Properties of Epoxy Coating

“…The peaks at 1715 cm −1 and 3430 cm −1 correspond to the stretching of C=O in the carboxyl group and the hydroxyl group with O–H stretching vibrations, respectively [ 35 ]. For ZIF–90/GO, another peak at 1675 cm −1 corresponds to the stretching vibration of C=O of the IC ligand of ZIF–90 [ 36 ]. The absorption peaks at 1200–1500 cm −1 are ascribed to the stretching vibrational bands of the IC ligand on ZIF–90.…”

Recent advances in the nanoarchitectonics of metal–organic frameworks for light-activated tumor therapy

“…70 In addition, compared with other nZIF delivery systems, ZIF-90 has not only better biocompatibility and chemical stability, but also the ability to perform post-synthetic modification through the free formaldehyde functional group attached to the imidazolic acid linking main chain, which has received extensive attention in recent years. 71 Therefore, studies have taken advantage of this feature to covalent nZIF-90 with the amino group of Arg-Gly-Asp (RGD) homing peptide motif to form an active delivery system, 54 and take advantage of nZIF's macropore and effective drug release properties. 15 The RGDmodified cis-NZIF-90 has better biocompatibility, pH response, and better targeted antitumor properties.…”

ZIF-90-decorated silica nanoparticles with a spiky surface: a novel approach to drug delivery

“…16 However, ZIF-90 has limited cellular uptake 18 and low loading, mainly in small micropores, 16 and dose-dependent cytotoxicity due to the high zinc content of the carrier. 15,19 The incorporation of ZIF-90 with spiky silica presents a promising solution to address the current challenges. The covalent interaction between ZIF-90 and drug molecules facilitates high loading capacity, while the acid-responsive decomposition of ZIF-90 ensures controlled and pH-responsive drug release.…”