Integrated prodrug micelles with two-photon bioimaging and pH-triggered drug delivery for cancer theranostics

Abstract

Nanodrug carriers with fluorescence radiation are widely used in cancer diagnosis and therapy due to their real-time imaging, less side effect, better drug utilization as well as the good bioimaging ability. However, traditional nanocarriers still suffer from unexpectable drug leakage, unsatisfactory tumor-targeted drug delivery and shallow imaging depth, which limit their further application in cancer theranostics. In this study, an integrated nanoplatform is constructed by polymeric prodrug micelles with two-photon and aggregation-induced emission bioimaging, charge reversal and drug delivery triggered by acidic pH. The prodrug micelles can be self-assembled by the TP-PEI (DA/DOX)-PEG prodrug polymer, which consists of the two-photon fluorophore (TP), dimethylmaleic anhydride (DA) grafted polyethyleneimine (PEI) and polyethylene glycol (PEG). The PEG segment, DOX and DA are bridged to polymer by acid cleavable bonds, which provides the micelles a ‘stealth’ property and a satisfactory stability during blood circulation, while the outside PEG segment is abandoned along with the DA protection in the tumor acidic microenvironment, thus leading to charge reversal-mediated accelerated endocytosis and tumor-targeted drug delivery. The great antitumor efficacy and reduced side effect of these pH-sensitive prodrug micelles are confirmed by antitumor assays in vitro and in vivo. Meanwhile, these micelles exhibited great deep-tissue two-photon bioimaging ability up to 150 μm in depth. The great antitumor efficacy, reduced side effect and deep two-photon tissue imaging make the TP-PEI (DA/DOX)-PEG prodrug micelles would be an efficient strategy for theranostic nanoplatform in cancer treatment.

Poly(lactic Acid): A Versatile Biobased Polymer for the Future with Multifunctional Properties—From Monomer Synthesis, Polymerization Techniques and Molecular Weight Increase to PLA Applications

“…ROP is executed typically in the presence of metal carboxylate with a hydroxyl-containing compound, normally alcohols, H 2 O, or macromolecules with hydroxy end group (denoted as ROH). Poly(ethylene glycol) (PEG) is one of the most common hydroxyl-containing chemicals in assisting synthesis of polyesters, and PEG itself is a hydrophilic polymer which has been widely applied as medical excipient and bio-matrix [ 49 , 50 , 51 ].…”

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

“…64 The pH-responsive AIEgen platform (such as drug molecules grafted pH-responsive polymer with AIE characteristics 65,66 ) induces fluorescence imaging capabilities and deliver therapeutic molecules to eliminate tumor upon a trigger by the acidic tumor environment. 67,68 Such pH-responsive AIE theranostic system specifically light up the tumor and deliver drug molecule avoiding damage to the surrounding normal cells. 69 Owing to the needs in the biological application, the characteristics of AIEgens are integrated for multifunction biomedical applications, such as imaging and image-guided theranostic applications.…”

Recent Advances in Biomedical Applications of Polymeric Nanoplatform Assisted with Two-Photon Absorption Process

“…After cellular uptake, the elevated intracellular ROS can disrupt the boronic ester bond and trigger the release of Cap for effective tumor therapy. In a subsequent study, they have also reported another prodrug micellar system with a neutral hydrophilic pH-detachable PEG shell and a dimethylmaleic anhydride-grafted-polyethyleneimine segment charge reversable segment [ 71 ]. While the AIE two-photon probe was chemically conjugated to the hydrophobic chain end, the therapeutic drug DOX was conjugated to the main backbone via an acid-labile imine bond.…”