Jinhwan Kim

Light-Induced Acid Generation on a Gatekeeper for Smart Nitric Oxide Delivery.

We report herein the design of a light-responsive gatekeeper for smart nitric oxide (NO) delivery. The gatekeeper is composed of a pH-jump reagent as an intermediary of stimulus and a calcium phosphate (CaP) coating as a shielding layer for NO release. The light irradiation and subsequent acid generation are used as triggers for uncapping the gatekeeper and releasing NO. The acids generated from a light-activated pH-jump agent loaded in the mesoporous nanoparticles accelerated the degradation of the CaP-coating layers on the nanoparticles, facilitating the light-responsive NO release from diazeniumdiolate by exposing a NO donor to physiological conditions. Using the combination of the pH-jump reagent and CaP coating, we successfully developed a light-responsive gatekeeper system for spatiotemporal-controlled NO delivery.

Doxorubicin/Ce6-Loaded Nanoparticle Coated with Polymer via Singlet Oxygen-Sensitive Linker for Photodynamically Assisted Chemotherapy

It is widely known that the therapeutic effect of nanoparticle-based chemotherapeutics could be greatly enhanced by the introduction of the photodynamic effect. Herein we report a chlorin e6-incorporated mesoporous silica nanoparticles (MSNs) covered with a polyethylene glycol shell conjugated via a singlet oxygen-sensitive labile bis(alkylthio)alkene linker (CeAP-L-PEG). In this study, single irradiation with biocompatible red light induced both intracellular doxorubicin release and photochemical internalization, and consequently enhanced anti-cancer effect was observed in vitro and in vivo. This study suggests the potential of our precisely designed nanoparticle system for photodynamically assisted chemotherapy.

An optical switch with newly designed electrostatic actuators for optical cross connects

We have developed an optical switch having low voltage driven electrostatic actuators and measured its optical performance. The simple structure of the actuator makes the fabrication process easy, helping to yield a low-cost device. In addition, a low-voltage actuating mechanism also provides good compatibility with IC and a simple driving circuit.

Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy

Since the discovery that nano-scaled particulates can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect, such nanostructures have been exploited as therapeutic small molecule delivery systems. However, the convoluted synthetic process of conventional nanostructures has impeded their feasibility and reproducibility in clinical applications. Herein, we report an easily prepared formulation of self-assembled nanostructures for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride). pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of 1:1, 2:1, and 4:1, respectively, to investigate the function of the residual PBA moiety as a targeting ligand. An acid-labile drug release profile was observed, owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor-targeting ability of the nanocomplexes was demonstrated, both in vitro by confocal microscopy and in vivo by fluorescence imaging, to be driven by an inherent property of the residual PBA. Ligand competition assays with free PBA pre-treatment demonstrated the targeting effect of the residual PBA from the nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free DOX, exhibited significantly greater anti-cancer effects in vitro and even in vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled nanostructures with potential biomedical applications.

Synthesis and Characterization of Nitric Oxide-Releasing Platinum(IV) Prodrug and Polymeric Micelle Triggered by Light

Herein, we report the proof of concept of photoresponsive chemotherapeutics comprising nitric oxide-releasing platinum prodrugs and polymeric micelles. Photoactivatable nitric oxide-releasing donors were integrated into the axial positions of a platinum(IV) prodrug, and the photolabile hydrophobic groups were grafted in the block copolymers. The hydrophobic interaction between nitric oxide donors and the photolabile groups allowed for the loading of platinum drugs and nitric oxide-releasing donors in the photolabile polymeric micelles. After cellular uptake of micelles, light irradiation induced the release of nitric oxide, which sensitized the cancer cells. Simultaneously, photolabile hydrophobic groups were cleaved from micelles, and the nitric oxide-releasing donor was altered to be more hydrophilic, resulting in the rapid release of platinum(IV) prodrugs. The strategy of using platinum(IV) prodrugs and nitric oxide led to enhanced anticancer effects.

A Pt(iv)-mediated polymer architecture for facile and stimuli-responsive intracellular gene silencing with chemotherapy

Conventional chemotherapy has been impeded by the inherent characteristics of cancer including fast mutagenesis and drug resistance; thus a combination therapy consisting of multiple therapeutic strategies has attracted much attention. However, the loading processes of multiple therapeutic molecules affect each other; thus the development of a nanocarrier that enables independent loading of the cargo molecules has been demanded. Herein, we report an ingeniously designed Pt(iv)-mediated polymeric architecture (Pt-PA) for combinatorial gene and chemotherapy to address the issue, prepared by crosslinking a cationic polymer (polyethylenimine, PEI) with a Pt(iv) prodrug. Therapeutic siRNA (anti-BCL2) was simply loaded by electrostatic interaction to form a stable nanocomplex. In the cellular study, the simultaneous release of both the active Pt(ii) drug and siRNA was monitored under the intracellular reducing environment, driven by dissociation of the polymer architecture due to an inherent characteristic of the Pt(iv) crosslinker. Therefore, an enhanced gene silencing effect and an anticancer effect were observed. Furthermore, in the animal study, an improved therapeutic effect of the nanocomplex was observed, which can be explained by tumor targeting via the EPR effect, and enhanced drug and siRNA release at the intracellular environment simultaneously. Taken together, the overall results from in vitro and in vivo studies strongly suggest the therapeutic potential of our precisely designed Pt(iv)-mediated polymer architecture.