Harnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer

Abstract

Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.

Chemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy

“…A number of studies have reported the successful use of phototherapy, such as PTT and photodynamic therapy (PDT), in the treatment of cancers [41][42][43][44][45][46] . In our study, PTT only moderately delayed the tumor growth.…”

Tumor‐Microenvironment‐Triggered Ion Exchange of a Metal–Organic Framework Hybrid for Multimodal Imaging and Synergistic Therapy of Tumors

“…[ 1–7 ] With the development of nanotechnology, many NTAs with imaging capabilities including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA) imaging and therapeutic functions including photodynamic therapy (PDT), photothermal therapy (PTT), or chemodynamic therapy (CDT) have been extensively developed. [ 8–18 ] However, most of reported NTAs suffer from their poor tumor specificity and unsatisfactory therapeutic efficiency due to the severe background interference during metabolism caused by the “always on” model. [ 19–21 ] To solve this problem, in situ NTA synthesis strategy to activate pro‐NTAs (precursor of NTAs) into NTAs at desired locations has attracted increasing attention.…”

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

“…Autophagy is an evolutionarily conservative modulatory process in which intracellular protein aggregates and impaired organelles are degraded via the lysosomal pathway for synthesizing new essential macromolecules to maintain homeostasis . Autophagic activity can be triggered under hypoxia, starvation, endoplasmic reticulum stress, mitochondrial damage, or exposure to nanomaterials . Elevated autophagic activity induced by nanomaterials reflects cellular response and oftentimes has a profound impact on cell fate, promoting either death or survival .…”