Nano-palladium is a cellular catalyst for in vivo chemistry

Abstract

Palladium catalysts have been widely adopted for organic synthesis and diverse industrial applications given their efficacy and safety, yet their biological in vivo use has been limited to date. Here we show that nanoencapsulated palladium is an effective means to target and treat disease through in vivo catalysis. Palladium nanoparticles (Pd-NPs) were created by screening different Pd compounds and then encapsulating bis[tri(2-furyl)phosphine]palladium(II) dichloride in a biocompatible poly(lactic-co-glycolic acid)-b-polyethyleneglycol platform. Using mouse models of cancer, the NPs efficiently accumulated in tumours, where the Pd-NP activated different model prodrugs. Longitudinal studies confirmed that prodrug activation by Pd-NP inhibits tumour growth, extends survival in tumour-bearing mice and mitigates toxicity compared to standard doxorubicin formulations. Thus, here we demonstrate safe and efficacious in vivo catalytic activity of a Pd compound in mammals.

Fluorescent and Biocompatible Ruthenium‐Coordinated Oligo(p‐phenylenevinylene) Nanocatalysts for Transfer Hydrogenation in the Mitochondria of Living Cells

“…It requires the metal catalysts to possess many properties including good biocompatibility, stability in physiological conditions, certain water dispersibility as well as hydrophobicity for easy uptake by cells, high activity, etc. Despite of these challenges, numerous metal catalysts have been successfully developed for intracellular catalysis, including metal nanoparticles, entrapped metal nanoparticles and metal complexes . However, fluorescent traceable metal catalysts that can target specific subcellular organelles with good intracellular catalysis ability have been rarely reported.…”

Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems

“…Although nanoparticles containing either palladium [64][65][66] or gold [67,68] have been used successfully to uncage molecules inside cells, soluble catalysts based on these metals are rare. A unique example is ar eport in 2017b yB radley and co-workers that homogeneousp alladium-carbene complexes are catalytically active inside prostate cancer cells.…”

Therapeutic Nanoreactors as In Vivo Nanoplatforms for Cancer Therapy

“…In particular,m icelle nanoassemblies can be regardeda sa promising nanoplatformt oi mmobilize and control the activities of highly stable synthetic catalysts, such as metallozymes or nanozymes, which can mimic naturale nzyme activities in therapeutic-related applications.F or example, Weissledera nd co-authorsr ecently utilized palladium catalysts to catalyze intracellularr eactions by uncaging variousm odel prodrugs including doxorubicin prodrug (pro-DOX)f or efficient tumor treatment in vivo. [18] Given the fact that Pd can, fore xample, efficiently cleave allyloxycarbonyl (alloc) groups under biological conditions as evidenced from their preliminary tests, they encapsulated Pd II catalysts into the micellar core of diblock amphiphilic copolymers poly(lactic-co-glycolic acid)-PEG( PLGA-PEG) nanoparticles, denoted as Pd-NP,w hich was intravenously delivered into the various tumor cell models in advance by meanso ft he EPR effect ( Figure 8C). After 5h,am odel chemodrug DOX, protected with an alloc ligand (Alloc-DOX) at its active daunosamine amino group to form pro-DOX,w as also systemically delivered to the tumor site.…”

“…C) Schematic representation of synthetic route for Pd II catalysts and its encapsulation into PLGA-PEGnanoparticle to form Pd-NP.D)Scheme demonstration for proDOXprodrug activation mediated by Pd catalystthrough the allylcarbamate cleavage to produce free cytotoxic DOX.E)HT1080tumorg rowth profile duringt reatment. F) Pie chart demonstrating distribution of nuclear DOX accumulationino rthotopic ovarian tumours and key organsr elated to toxicity.A),B) Reprinted with permission form reference [31c];Copyright Wiley-VCH 2016.C )-F) Reprinted withp ermission form reference[18];Copyright Springer Nature 2017.…”