Selective cancer treatment via photodynamic sensitization of hypoxia-responsive drug delivery

Abstract

The precise and selective delivery of chemodrugs into tumors represents a critical requirement for anti-cancer therapy. Intelligent delivery systems that are responsive to a single internal or external stimulus often lack sufficient cancer selectivity, which compromises the drug efficacy and induces undesired side effects. To overcome this dilemma, we herein report a cancer-targeting vehicle which allows highly cancer-selective drug release in response to cascaded external (light) and internal (hypoxia) dual triggers. In particular, doxorubicin (DOX)-loaded, hypoxia-dissociable nanoparticles (NPs) were prepared from self-assembled polyethylenimine-nitroimidazole (PEI-NI) micelles that were further co-assembled with hyaluronic acid-Ce6 (HC). Upon accumulation in tumor cells, tumor site-specific light irradiation (660 nm, 10 mW cm) generated high levels of reactive oxygen species (ROS) and greatly enhanced the hypoxic levels to induce NP dissociation and accordingly DOX release. A synergistic anti-cancer efficacy between DOX-mediated chemotherapy and Ce6-mediated photodynamic therapy (PDT) was thus achieved, resulting in reduced side effects to normal tissues/cells. This study therefore provides an effective method to control the cancer-specific drug delivery by responding to cascaded multiple triggers, and it renders promising applications for the programmed combination of chemotherapy and PDT toward cancer treatment.

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

“…a Fabrication of DOX-loaded PEI-NI-based nanoparticle co-assembled with HA-Ce6, ( b ) CD 44-mediated endocytosis and release of DOX in response to hypoxia generated by laser irradiation. Reproduced with permission [ 65 ] of The Royal Society of Chemistry …”

Fighting Hypoxia to Improve PDT

“…He et al [170] reported a cancer-targeting vehicle characterized by cascaded reactivity to external (light) and internal (hypoxia) triggers for selective release of the cancer drug. The hypoxia-responsive drug delivery was prepared from self-assembled polyethylenimine-nitroimidazole (PEI-NI) micelles loaded with DOX that were further co-assembled with HA-conjugated Ce6 (HC) to form NPs.…”

MFP-FePt-GO Nanocomposites Promote Radiosensitivity of Non-Small Cell Lung Cancer Via Activating Mitochondrial-Mediated Apoptosis and Impairing DNA Damage Repair

“…However, the application of nitroimidazole in clinic is limited by its high toxicity [17]. Therefore, the predicable solution of its employment as a radiosensitizer involves transporting nitroimidazole into tumor area by a nano drug delivery system and minimizing the normal tissue cytotoxicity [18]. In addition, 5-fluorouracil (5-FU) was applied as deoxy thymidylate synthetase inhibitor in concurrent chemoradiotherapy to impair DNA synthesis in lung cancer treatment.…”