Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy

Abstract

Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes, and shapes; high drug loadings; ease of surface modification; and intrinsic biodegradability. Here we report the self-assembly of zinc bisphosphonate NCPs that carry 48±3 wt% cisplatin prodrug and 45±5 wt% oxaliplatin prodrug. In vivo pharmacokinetic studies in mice show minimal uptake of pegylated NCPs by the mononuclear phagocyte system and excellent blood circulation half-lives of 16.4±2.9 and 12.0±3.9 h for the NCPs carrying cisplatin and oxaliplatin, respectively. In all tumor xenograft models evaluated, including CT26 colon cancer, H460 lung cancer, and AsPC-1 pancreatic cancer, pegylated NCPs show superior potency and efficacy compared to free drugs. As the first example of using NCPs as nanotherapeutics with enhanced antitumor activities, this study establishes NCPs as a promising drug delivery platform for cancer therapy.

Coadministration of Vascular Disrupting Agents and Nanomedicines to Eradicate Tumors from Peripheral and Central Regions

“…Free CA4P typically produces massive necrosis within Nanosized anticancer drug delivery systems hold great promise for safe, simple, and effective therapies against malignant solid tumors. [1][2][3][4][5] Nanoparticles accumulate in solid tumors by virtue of size and longevity in blood circulation due to the enhanced permeability and retention (EPR) effect. [ 6,7 ] This phenomenon was reported by Maeda and Matsumura in the mid-1980s and has since been confi rmed by a fl ood of preclinical studies of drug-loaded nanoparticles.…”

Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles

“…Further modifications are sought to address drawbacks of poor solubility, rapid clearance, and a lack of selectivity (5,6). Although fluorescence-based techniques provide a means to track the processes of translocation, drug release and excretion of anticancer agents, the aforementioned species are intrinsically nonfluorescent under treatment conditions (7)(8)(9)(10).…”

Hybrid Nanoparticles for Cancer Imaging and Therapy

“…This method was also used to synthesize NMOFs capped with lipid, such as 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA). Several DOPA-coated NMOFs were synthesized by utilizing the surfactant-templated solvothermal reactions, including Zr-methotrexate (MTX) NMOFs, Zn-MTX NMOFs, La-DSCP NMOFs, and Zn bisphosphonate NCP containing platinum-based prodrugs [49,54,55]. The four general methods described above have been adopted to synthesize a large number of NMOFs.…”

“…These loading methods fall into two main categories: Direct incorporation during NMOF synthesis and postsynthetic loading [26,27]. Imaging or therapeutic agents can be directly incorporated into the NMOF structure during synthesis as metal-connecting points/clusters or as the bridging ligand [33,48,52,53,56,57] 2 ] 2 ), gemcitabine monophosphate, 2,3,5,6-tetraiodo-1,4-benzenedicarboxylic acid (I 4 -BDC) were adopted as bridging ligands to form NMOFs to provide chemotherapeutics cisplatin, oxaliplatin, and gemcitabine for cancer therapy and high Z element iodine for CT imaging [48,55,56]. This strategy can lead to NMOFs possessing very high agent loadings with uniform distribution throughout the frameworks.…”