pH-Responsive NIR-Absorbing Fluorescent Polydopamine with Hyaluronic Acid for Dual Targeting and Synergistic Effects of Photothermal and Chemotherapy.

ABSTRACT

In cancer therapy, optimizing tumor-specific delivery, tumor distribution, and cellular uptake of a drug is important for ensuring minimal toxicity and maximum therapeutic efficacy. This study characterized the therapeutic efficacy of a stimulus responsive and dual targeting nanocarrier for a bioimaging-guided photothermal and chemotherapeutic platform. Hyaluronic acid (HA) conjugated with triphenylphosphonium (TPP) and boronic acid (BA) diol-linked ß-cyclodextrin (ß-CD) forms an inclusion complex with paclitaxel (PTX), creating a shell-like composite on a core of carbonized fluorescent polydopamine nanoparticles (FNPs-pDA) applicable for photothermal therapy as well as bioimaging. The successful diol cross-linking between core@shells generates nanocarriers [FNPs-pDA@HA-TPP-CD-PTX] that can be used as an extracellular HA- and intracellular TPP-mediated dual targeting system. The carbonized FNPs-pDA was cross-linked with the boronic acid groups of HA-TPP-CD-PTX to promote the formation of boronate esters for pH-mediated photothermal activity, which have shown time dependent complete PTX release along with a photothermal mediated response. The in vitro dual bioimaging and photothermal-chemotherapeutic activities were compared between cancer and normal cells. Lysosomal escape and live/dead cells staining confocal images highlight the promise of this system, which might open up a new approach, a simple and versatile method for site-specific synergetic drug delivery.