Acid‐triggered synergistic chemo‐photodynamic therapy systems based on metal‐coordinated supramolecular interaction

Abstract

To enhance anticancer efficacy and decrease side effects, the synergistic multi-agent therapy has now increasingly gotten great attention. Herein, the flexible polycaprolactone had been modified by histidine and formed assembles with PEGylated metallo-porphyrin via metal-coordinated supramolecular interaction. This supramolecular assembles showed excellent acid sensitivity. At neutral environment, the hydrophobic anticancer drug could be effectively co-encapsulated with photosensitizer Fe-TPP to improve the water solubility. While at the intracellular microenvironment, the changed acid environment would trigger the drug and Fe-TPP release due to the reduction of metal-coordinated interaction between histidine and metallo-porphyrin leading to the disintegration of assembles. The in vivo anticancer experiments toward HeLa and MCF-7 cells disclosed that this co-delivery system of anticancer drug and photosensitizer showed enhanced anticancer efficacy, implying that the synergistic chemo-photodynamic therapy could improve cellular proliferation inhibition. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2955-2962, 2018.

Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy

“…Thus, ROS cause damage to the whole cell and contribute to a great number of pathological conditions. [43] Abnormal ROS expression in tumor tissues is one of the typical examples; other examples include hypertension and inflammation. [17,46] In particular, ROS levels in tumor tissue are predominantly greater than that of healthy tissue due to the accumulation of reactive molecules from the hypoxic conditions in cancer tissue.…”

“…On the other hand, tumor cells may develop resistance to antitumor drugs, which often limits the clinical application of anticancer drugs; a problem that needs to be urgently settled. [3,43] Gene therapy for tumors has advantages of high specificity and low toxicity compared to chemotherapy, but the transfection efficiency of the active gene is low, resulting in the less effective treatment of malignant tumors. [15] Codelivery of anticancer drugs and genes improves the therapeutic effect, reduces toxicity, and overcomes multidrug resistance of anticancer drugs.…”

“…Combination therapy is the latest and most significant development in cancer treatment. [ 43 ] The environment in the human body is complex and changeable, and the DDSs are confronted with a series of obstacles from blood, tumor tissue, cancer cells, and organelles. Although stand‐alone stimuli‐responsive self‐assembled NPs possess many advantages, they cannot overcome all obstacles.…”

“…Among these multistimuli responses, diselenide bonds are a unique dual redox response that responds to oxidants or reductants at the same time. Additionally, the combination of redox‐responsive nanosystem and other treatments (photodynamic therapy (PDT), [ 43 ] or heating treatment [ 106 ] ) is popularly applied for cancer therapy.…”

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

“…Chen and coworkers reported two distinct acid-triggered micellar systems for synergistic chemo-photodynamic therapy employing DOX, a hydrophobic anticancer drug, and iron(II) tetraphenylporphyrin (FeTPP) [ 90 , 151 ]. In the first work, they designed micelles obtained by the self-assembling histidine modified-PLA and PEG conjugated to FeTPP ( Fe1 ) [ 90 ].…”