Fabrication of Charge-Conversion Nanoparticles for Cancer Imaging by Flash Nanoprecipitation

Abstract

Traditional charge-conversion nanoparticles (NPs) need the breakage of acid-labile groups on the surface, which impedes the rapid response to the acidic microenvironment. Here, we developed novel rodlike charge-conversion NPs with amphiphilic dextran- b-poly(lactic- co-glycolic acid), poly(2-(dimethylamino) ethylmethylacrylate)- b-poly(ε-caprolactone), and an aggregation-induced emission-active probe through flash nanoprecipitation (FNP). These NPs exhibit reversible negative-to-positive charge transition at a slightly acidic pH relying on the rapid protonation/deprotonation of polymers. The size and the critical charge-conversion pH can be further tuned by varying the flow rate and polymer ratio. Consequently, the charge conversion endows NPs with resistance to protein adsorption at physiological pH and enhanced internalization to cancer cells under acidic conditions. Ex vivo imaging on harvest organs shows that charge-conversion NPs were predominantly distributed in tumors after intravenous administration to mice due to the robust response of NPs to the acidic microenvironment in tumor tissue, whereas control NPs or free probes were broadly accumulated in tumor, liver, kidney, and lung. These results suggest the great potential of the current FNP strategy in the facile and generic fabrication of charge-conversion NPs for tumor-targeting delivery of drugs or fluorescent probes.

A pH‐Sensitive Self‐Assembled and Carrier‐Free Nanoparticle Based on Charge Reversal for Enhanced Synergetic Chemo‐Phototherapy

“…Charge-reversal property played a vital role in the circulation during physical environment and enhanced cellular endocytosis in the tumor acid environment. The tertiary amino groups of PDMAEMA protonated [31,35] under acidic tumor conditions that eventually lead to the negative-to-positive charge reversal of DZP NPs. Imitating the normal physical conditions and the tumor acid environment, DZP was used to display the charge-reversal studies.…”

“…PDMAEMA-PHB-PDMAEMA, with two hydrophilic poly blocks and a central hydrophobic poly block, has richly tertiary amino groups that is simple to protonate in acid conditions. [30,31] Therefore, a novel Dox and ZnPc co-loaded charge-reversal nanoparticle drug delivery system was prepared for tracking drug distribution and effectively eradicating tumors by a synergistic therapy without recurrence during one treatment cycle.…”

Critical considerations for targeting colorectal liver metastases with nanotechnology

“…This has been exploited through the fabrication of charge-conversion NPs which aim to facilitate improved tumor cell entry. The underlying mechanism is to switch the charge of the NP in response to the microenvironment it is exposed to (Cai & Mao, 2016;M. Li et al, 2018).…”

Biodegradable Nanoparticles of Polyacrylic Acid–Stabilized Amorphous CaCO3 for Tunable pH‐Responsive Drug Delivery and Enhanced Tumor Inhibition

“…Nanoparticle (NP)‐based drug delivery system has been demonstrated as a robust strategy to improve the bioavailability of therapeutic agents and overcome biological barriers both in vitro and in vivo . NPs involve a wide range of nanomaterials from liposomes and polymers to inorganic compounds and hybrid materials . Among them, inorganic nanocarriers show great advantages such as the facile fabrication and large specific surface area .…”