Rapid and Versatile Construction of Diverse and Functional Nanostructures Derived from a Polyphosphoester-Based Biomimetic Block Copolymer System

Abstract

A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures, and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable polyphosphoester block copolymer system. From a retrosynthetic point of view, the non-ionic, anionic, cationic and zwitterionic micelles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock polyphosphoester by “click” type thiol-yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock polyphosphoester was synthesized by an ultrafast (< 5 min) organocatalyzed ring-opening polymerization in a two-step, one-pot manner with the quantitative conversions of two kinds of cyclic phospholane monomers. The whole programmable process starting from small molecules to nanoparticles could be completed within 6 h, as the most rapid approach for the anionic and non-ionic nanoparticles, although the cationic and zwitterionic nanoparticles required ca. 2 days due to purification by dialysis. The micelles showed high biocompatibility, with even the cationic micelles exhibiting a 6-fold lower cytotoxicity toward RAW 264.7 mouse macrophage cells, as compared to the Lipofectamine® commercial transfection agent.

Smart Stimuli-Responsive Nano-sized Hosts for Drug Delivery

“…As an example of all stemming from a polyphosphoester block copolymer system that is biodegradable in nature, variation of nanoparticles' surface charge/functionality will quickly and simply yield pH-sensitive block copolymers [ 48 ]. Micelle formation (i.e., positive, negative, neutral, zwitterionic) occurred rapidly when various amphiphilic diblock polyphosphoesters were separately suspended in water [ 48 ].…”

“…Micelle formation (i.e., positive, negative, neutral, zwitterionic) occurred rapidly when various amphiphilic diblock polyphosphoesters were separately suspended in water [ 48 ]. Figure 1.3 represents an illustration of different types of micelles, adapted from Wooley et al's report [ 48 ].…”

“…Figure 1.3 represents an illustration of different types of micelles, adapted from Wooley et al's report [ 48 ]. These micelles showed high biocompatibility and low cytotoxicity and are attractive for drug delivery purposes [ 48 ].…”

Low-Temperature Processable Block Copolymers That Preserve the Function of Blended Proteins

“…16−18 Compared with conventional aliphatic polyesters, the molecular functionalization of polyphosphoesters is easier because various cyclic phosphoesters, which work as monomers, can be obtained by a simple condensation reaction between an alcohol and 2-chloro-2-oxo-1,3,2-dioxaphosphorane (COP). 19,20 That is, theoretically, any alcohol can be introduced into polyphosphoesters. Furthermore, the solubility of polyphosphoesters can be controlled by the substituent groups on the side chain.…”

Investigating the pharmacokinetics and biological distribution of silver‐loaded polyphosphoester‐based nanoparticles using 111Ag as a radiotracer

“…[12] Here, the next generation polyphosphoester-based degradable SCKs were used as biocompatible, biodegradable vehicles with superior loading and dosing capabilities, which would allow for improved sustained release of the therapeutic silver ions in the lungs. [20] In this work, we evaluated the pharmacokinetics (PK) and biodistribution (bioD) of silver loaded polyphosphoester-based degradable and hydrocarbon-based non-degradable SCK nanoparticles and compared our findings to our previous work with a silver N-heterocyclic carbene complex (SCC1), using 111 Ag as a radiotracer.…”