Real-Time Monitoring of Anticancer Drug Release with Highly Fluorescent Star-Conjugated Copolymer as a Drug Carrier

Abstract

Chemotherapy is one of the major systemic treatments for cancer, in which the drug release kinetics is a key factor for drug delivery. In the present work, a versatile fluorescence-based real-time monitoring system for intracellular drug release has been developed. First, two kinds of star-conjugated copolymers with different connections (e.g., pH-responsive acylhydrazone and stable ether) between a hyperbranched conjugated polymer (HCP) core and many linear poly(ethylene glycol) (PEG) arms were synthesized. Owing to the amphiphilic three-dimensional architecture, the star-conjugated copolymers could self-assemble into multimicelle aggregates from unimolecular micelles with excellent emission performance in the aqueous medium. When doxorubicin (DOX) as a model drug was encapsulated into copolymer micelles, the emission of star-conjugated copolymer and DOX was quenched. In vitro biological studies revealed that fluorescent intensities of both star-conjugated copolymer and DOX were activated when the drug was released from copolymeric micelles, resulting in the enhanced cellular proliferation inhibition against cancer cells. Importantly, pH-responsive feature of the star-conjugated copolymer with acylhydrazone linkage exhibited accelerated DOX release at a mildly acidic environment, because of the fast breakage of acylhydrazone in endosome or lysosome of tumor cells. Such fluorescent star-conjugated copolymers may open up new perspectives to real-time study of drug release kinetics of polymeric drug delivery systems for cancer therapy.

Smart surface-enhanced Raman scattering traceable drug delivery systems

“…1,2 For the improvement of the practical and clinical performances of drugs to combat human cancer, nanoparticle-based drug delivery systems (DDSs) have, over the recent years, drawn worldwide attention in the field of anticancer research. For example, impressive efforts have been made to construct physical featurecontrolled, 3,4 highly biocompatible 5 and multifunctional 6 DDSs.…”

Protein‐Framed Multi‐Porphyrin Micelles for a Hybrid Natural–Artificial Light‐Harvesting Nanosystem

“…Previously, our group disclosed a special multimolecular micelle structure, named as unimolecular micelle aggregate (UMA), through the direct aggregation of unimolecular micelles into a pomegranate-like micellar structure. [13] In the present work, a four-arm star polymer (THPD) with a porphyrin core and four poly(2-(Dimethylamino)ethylmethacrylate) (PDMAEMA) arms was synthesized, which also self-assembled into the pomegranate-like UMAs in water (Scheme 1). Since the obtained THPD micelles have multi-porphyrin donors, a biomimetic LHA system with multiple donors and one acceptor could be constructed if an acceptor was able to be introduced into the core of the THPD micelle.…”

“…Thus, the THPD micelles should have a so-called UMA structure as shown in Scheme 1. [13] In other words, the THPD micelles were formed through the direct aggregation of THPD unimolecular micelles.Such a UMA structure can effectively inhibit the selfquenching between porphyrin chromophores. ZnTHPPs are not water-soluble and will undergo serious aggregationcaused quenching (ACQ) with the increase of concentration.…”

Synthesis and self-assembly in bulk of star-shaped block copolymers based on helical polypeptides

“…Compared with linear block copolymers, recently, star block copolymers have attracted increasing attentions and have found miscellaneous applications in bulk or in selective solution owing to their wide range of phase-separation morphologies in nanometer size range [1][2][3]. These properties make star block copolymer materials useful as drug nanocarriers, diagnose assays, nanopatterns, and photonics [4][5][6][7][8] and also provoke considerable interests in synthesis of various star copolymers with different morphologies by varying arm numbers, chemical compositions, and molecular weights of arm building blocks.…”

“…These properties make star block copolymer materials useful as drug nanocarriers, diagnose assays, nanopatterns, and photonics [4][5][6][7][8] and also provoke considerable interests in synthesis of various star copolymers with different morphologies by varying arm numbers, chemical compositions, and molecular weights of arm building blocks. For linear block copolymers, the morphologies (such as lamellae, cylinders, gyroids, and spheres) are determined by three parameters, including (1) the volume fraction of one component f, (2) the total degree of polymerization N of the block copolymer, and (3) the Flory-Huggins interaction parameter χ. Compared with coil-coil block copolymers, rod-coil block copolymer have high Flory-Huggins interaction parameter χ that it can allow microphase separation to occur at relatively low degrees of polymerization and at a rather short length of a few nanometers, leading to unique and periodic patterns which have been widely investigated and reviewed during the last decade [9][10][11][12][13].…”