Acid-Responsive Polymeric Doxorubicin Prodrug Nanoparticles Encapsulating a Near-Infrared Dye for Combined Photothermal-Chemotherapy

Abstract

Combination therapy with high spatial and temporal resolution is highly promising for efficient medical treatment of cancer. In this study, doxorubicin (DOX) conjugated amphiphilic block copolymer with a terminal folic acid moiety was prepared, which could self-assemble into nanoparticles by encapsulating organic near-infrared (NIR) absorbing dye IR825 for combined photothermal-chemotherapy. The resulting PDOX/IR825 nanoparticles showed excellent colloidal stability and monodispersity in aqueous solution. Specifically, the conjugated DOX could be released quickly in weak acidic environment for chemotherapy due to the cleavage of acid-labile hydrazone bond. Meanwhile, the encapsulated dye could convert the NIR light energy into heat with high efficiency, which makes the self-assembled nanoparticles an effective platform for photothermal therapy. Confocal microscopy observations and flow cytometry analysis confirmed that the PDOX/IR825 nanoparticles could be efficiently endocytosed by HeLa cells and deliver DOX into the nuclei of cancer cells. The in vitro cell viability assays indicated that both DOX-sensitive HeLa cells and DOX-resistant A2780/DOX R cells were completely killed by the treatment of PDOX/IR825 under NIR light irradiation. Significant tumor regression was also observed in the zebrafish liver hyperplasia model upon combinational therapy provided from the PDOX/IR825 nanoparticles. Hence, the PDOX/IR825 nanoparticles exhibited a great potential in site-specific combined photothermal-chemotherapy of tumor.

Cancer‐Associated, Stimuli‐Driven, Turn on Theranostics for Multimodality Imaging and Therapy

“…The hydrazone bond is stable under neutral conditions but is quickly cleaved by aqueous acids. Using hydrazone as a linker, Zhang et al developed an acid responsive nanosystem for combined CHT and PTT ( Figure ) . In this system, DOX is conjugated to a FA modified amphiphilic block copolymer via a hydrazone linker.…”

“…Schematic illustration of a pH‐activatable polymer‐DOX‐near infrared dye nanosystem. Reproduced with permission . Copyright 2016, American Chemical Society.…”

Pt(II) complexes immobilized on polymer‐modified magnetic carbon nanotubes as a new platinum drug delivery system

“…The surface modification of CNTs with hydrophilic and stimuli‐sensitive polymers, in addition to increasing the water solubility of the carrier, can lead to controlled release of a loaded drug and thereupon increased efficacy and reduced side effects of the drug. For example, the creation of a pH‐sensitive binding site between drug and surface‐modifying polymer should help the selective release of anticancer drugs at diseased tissues because the pH in tumour tissues is lower than that in normal tissues (7.4) and intracellular pH of their endosomes and lysosomes is even more acidic (pH = 4.5–6.5) …”

Au Nanoclusters Sensitized Black TiO2−x Nanotubes for Enhanced Photodynamic Therapy Driven by Near‐Infrared Light

“…The photosensitizer is sensitized by light to disintegrate H 2 O/O 2 in the tissue for producing ROS to damage tumor cells . However, due to low tissue penetration depth of exciting light and thin oxygen content in the site of the tumor, the effectiveness of photodynamic therapy and the extending absorbs light range of photodynamic agent have aroused considerable efforts to exploit desired and alternative photosensitizer . The best ideal photodynamic agent is sensitized by visible or/and NIR light to obtain abundant ROS through disintegrating H 2 O/O 2 , and it should have excellent biocompatibility and stability in the course of treatment .…”