Construction and Characterization of PDA@MnO2-Cored Multifunctional Targeting Nanoparticles Loaded with Survivin siRNA for Breast Tumor Therapy

TL;DR

This study develops a new nanoparticle system that combines siRNA delivery and photothermal therapy to improve breast cancer treatment.

Contribution

A novel multifunctional nanoparticle with PDA@MnO2 core and survivin siRNA for targeted breast tumor therapy is developed.

Findings

PDA@Mn-siSur-c-NPs showed high siRNA protection and reduced toxicity.

The nanoparticles exhibited enhanced anti-tumor effects when combined with photothermal therapy.

Survivin protein expression was significantly downregulated in tumor tissues.

Abstract

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO2) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was employed to quantify manganese content. To assess siRNA stability within the system, samples were incubated with 50% fetal bovine serum (FBS) before agarose gel electrophoresis analysis. Additionally, cellular internalization by 4T1 cells and in vitro photothermal conversion efficiency of the formulation were evaluated. ICP-OES was further utilized to investigate the in vivo pharmacokinetics and tissue distribution of manganese. Animal model studies were conducted to assess the anti-breast cancer efficacy of PDA@Mn-siSur-c-NPs in combination with infrared irradiation. Results: The newly developed PDA@Mn-siSur-c-NPs demonstrated superior siRNA protection, reduced toxicity, and high photothermal conversion capacity. When combined with photothermal therapy (PTT), these nanoparticles exerted enhanced synergistic anti-tumor effects. Delivery of survivin siRNA resulted in a significant downregulation of survivin protein expression in tumor tissues. Moreover, magnetic resonance imaging (MRI) confirmed that the nanoparticles possess favorable imaging properties. Conclusions: This research demonstrates that the integration of PDA@Mn-siSur-c-NPs with PTT holds considerable therapeutic promise for improved breast cancer treatment.

Figures