Hyaluronic Acid-Functionalized Gold Nanorods with pH/NIR Dual-Responsive Drug Release for Synergetic Targeted Photothermal Chemotherapy of Breast Cancer

Abstract

Tumor-targeted delivery of photothermal agent and controlled release of concomitant chemotherapeutic drug are two key factors for combined photothermal chemotherapy. Herein, we developed a pH/near-infrared (NIR) dual-triggered drug release nanoplatform based on hyaluronic acid (HA)-functionalized gold nanorods (GNRs) for actively targeted synergetic photothermal chemotherapy of breast cancer. Targeting folate (FA), dopamine, and adipic acid dihydrazide triconjugated HA was first synthesized and used to decorate GNRs via Au-catechol bonds, and then an anticarcinogen doxorubicin (DOX) was conjugated onto HA moieties via an acid-labile hydrazone linkage, resulting in multifunctional nanoparticles GNRs-HA-FA-DOX. The nanoparticles exhibited excellent stability and had a pH and NIR dual-responsive drug release behavior. In vitro studies showed that the nanoparticles could be efficiently internalized into breast cancer MCF-7 cells and kill them under NIR irradiation in a synergistic fashion via inducing cell apoptosis. Pharmacokinetics and biodistribution studies in tumor-bearing mice indicated that the nanoparticles had a long blood circulation with a half-life of 2.4 h and exhibited a high accumulation of 11.3% in tumor site. The tumors of mice treated with combined chemotherapy and photothermal therapy were completely suppressed without obvious systemic toxicity after 20 d of treatment. These results demonstrated a great potential of GNRs-HA-FA-DOX nanoparticles for targeted synergistic therapy of breast cancer.

Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

“…Meanwhile, the long chain of HA could also act as gatekeeper to keep drug molecules inside the AuNFs. Under NIR‐II laser irradiation, the photothermal effect of AuNFs can loosen the structure of the HA layer and decrease the viscosity of HA, thereby enabling the release of cargo molecules. Taking advantage of the therapeutic endeavor to reduce tumorous HA by introduction of exogenous hyaluronidase‐1 (Hyal‐1), Hyal‐1‐triggerred release of cargos from HA‐coated AuNFs can be another appealing strategy.…”

“…Mater. 2020, 30,1908825 layer and decrease the viscosity of HA, [38] thereby enabling the release of cargo molecules. Taking advantage of the therapeutic endeavor to reduce tumorous HA by introduction of exogenous hyaluronidase-1 (Hyal-1), [39] Hyal-1-triggerred release of cargos from HA-coated AuNFs can be another appealing strategy.…”

Synergized Multimodal Therapy for Safe and Effective Reversal of Cancer Multidrug Resistance Based on Low‐Level Photothermal and Photodynamic Effects

“…Of note, the further involvement of NIR irradiation boosted DOX release to nearly 100% (Figure S12B,C, Supporting Information) due to the heat from PTE but not PDE (Figure S12D, Supporting Information). This heat might decrease the viscosity of surrounding fluids, favor the diffusion of DOX, and loosen the HA layer . Further, the positive correlation between DOX release rate and the laser power suggests an on‐demand, remote control over drug release (Figure S12E, Supporting Information).…”

“…This heat might decrease the viscosity of surrounding fluids, favor the diffusion of DOX, and loosen the HA layer. [14,31] Further, the positive correlation between DOX release rate and the laser power suggests an on-demand, remote control over drug release ( Figure S12E, Supporting Information). These results together indicate three features of DOX's controlled release from DOX@AuHCNs-HA: hyaluronidase responsive, acidity responsive, and heat accelerated.…”

Nanoparticles‐Mediated Combination Therapies for Cancer Treatment

“…[265,266] Further, multiple stimuli-responsive GNRs-based nanoformulations have been designed to achieve synergistic effect accompanied by controlled release of drugs. [267][268][269] One example is the immobilization of drug-loaded dendrimers on GNRs surface. [244] There, the drug was conjugated through hydrazine bond for pH-responsive drug release ( Figure 6).…”