Multistimuli‐Responsive Bilirubin Nanoparticles for Anticancer Therapy

Abstract

Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers,t heir clinical translation has been limited. Ideally,materials used for the purpose should be biocompatible and nontoxic,p rovide "on-demand" drug release in response to internal or external stimuli, allowl arge-scale manufacturing,a nd exhibit intrinsic anticancer efficacy.W ep resent multistimuli-responsive nanoparticles formed from bilirubin, ap otent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity.E xposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS)o re xternal laser light causes rapid disruption of the BRNP nanostructure as aresult of as witch in bilirubin solubility,t hereby releasing encapsulated drugs.I naxenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as ad rug-delivery carrier as well as ac ompanion medicine for effectively treating cancers.

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

“…Synthesis of PEGylated Bilirubin : According to the literature, 0.1 mmol of bilirubin and 0.12 mmol of EDC were dissolved in 2 mL of dimethyl sulfoxide (DMSO), and stirred at room temperature for 10 min. Then 0.06 mmol of PEG dissolved in DMSO and added to the mixture with 45 µL triethylamine.…”

“…However, one practical problem lies in the irresponsiveness of NDDSs towards the tumor microenvironment, which results in insufficient intratumoral drug release and more off‐target exposure . Thus, bilirubin, an endogenous hydrophobic antioxidant, can react with overproduced reactive oxygen species (ROS) inside tumors, turn into hydrophilic biliverdin and lead to on‐demand drug release . Unlike free bilirubin, the introduction of hydrophilic poly (ethylene glycol) (PEG) is seized upon as a solution to make hydrophobic one well‐dispersed in water and dramatically prolong the blood circulation .…”

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

“…Importantly, although the latter may have a significant contiguity to the field of ROS‐activated prodrugs, we will limit our attention here to the responsiveness of macromolecular structures. We will also mention only briefly cases of polymer‐linked ROS‐responsive low molecular compounds such as bilirubin …”

Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application To Protect Brain from Injury in Ischemic Stroke

“…18–20 Melanin, a heterogeneous biological polymer presenting in most organisms including human, has attracted increasing attention for molecular imaging and photothermal therapy, due to its intrinsic photoacoustic signal, strong chelating capability to metal ions, and near-infrared absorbance. 21–23 Melanin also plays an important role in protecting skin against ultraviolet (UV) irradiation, which is presumably attributable, at least in part, to its ability to intercept and deactivate radical species generated by UV light.…”