Targeted Nanoparticle-Based Therapies for Nasopharyngeal Carcinoma: Enhancing Radiosensitization, Photothermal Therapy, and Diagnostics

Abstract

Nasopharyngeal carcinoma (NPC) remains a major clinical challenge due to its high resistance to conventional therapies such as chemotherapy and radiotherapy. Nanoparticle (NP)-based technologies have emerged as promising tools to enhance the efficacy of NPC treatment through mechanisms like radiosensitization and photothermal therapy. This review discusses the potential of NPs, particularly metal-based nanoparticles (gold and iron oxide), in improving the therapeutic outcomes of radiotherapy by overcoming tumor hypoxia and increasing radiation absorption. Additionally, we explore the application of NPs in photothermal therapy, wherein nanoparticles absorb light and generate localized heat to target tumor cells with precision. NPs are also playing an increasingly vital role in early diagnosis and real-time imaging, enabling more effective monitoring and personalized treatment. Despite the promising potential, challenges as nanoparticle biocompatibility, toxicity, and efficient targeting remain obstacles for clinical translation. In this review, we aim to provide a comprehensive summary of the current state of targeted nanoparticle-based interventions in NPC therapy and to outline the potential for these technologies to improve therapeutic outcomes.

Keywords: nanomedicine; nanoparticle; nanotechnology; nasopharyngeal carcinoma; treatment.

Figure 1

Characterization of Pt-HFn Structure and Catalase-Like Activity. (a) Left: TEM image of Pt-HFn with negative staining, highlighting the morphology of the HFn shell. Right: Particle size distribution of HFn derived from TEM analysis. Scale bar, 10 nm. (b) Left: TEM image of Pt-HFn without negative staining, revealing the morphology of the Pt core. Right: Size distribution of the Pt core from TEM analysis. Scale bar, 10 nm. (c) High-resolution TEM image of the Pt core within Pt-HFn, with insets showing atomic-level images of selected areas and their corresponding fast Fourier transform (FFT) patterns. Scale bar, 2 nm. (d) TEM-EDS spectrum of Pt-HFn, with the inset displaying the mass and atomic percentages of the elements present in the sample. (e) Upper: Diagram illustrating the catalase-like activity of Pt-HFn in decomposing H₂O₂ to produce O₂. Lower: Photographs showing the generation of O₂ bubbles in H₂O₂ solutions for each group. (f) Absorbance changes at 240 nm, indicating H₂O₂ reduction in solutions for each group (n = 4 independent experiments). (g) Changes in dissolved oxygen levels demonstrate increased O₂ content in H₂O₂ solutions for each group (n = 3 independent experiments). Data are presented as mean ± SEM. Reproduced from Zhang R, Shen Y, Zhou X, et al. Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization. Nat Commun. 2025;16(1):890. Copyright © 2025, The Author(s). This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 2

Schematic diagrams of α-NTP and α-NTP-LNs illustrate the targeting mechanism. α-NTP-LNs were shown to specifically target NPC, demonstrating the combined synergistic effect of the α-peptide and NTP within the α-NTP fusion peptide for enhanced targeting. Reproduced from Luo H, Lu L, Yang F, et al. Nasopharyngeal cancer-specific therapy based on fusion peptide-functionalized lipid nanoparticles. ACS Nano. 2014;8(5):4334–4347. Copyright 2014, American Chemical Society.

Figure 3

Enhancement of Radiosensitivity in NPC Using Fe@Pdots-siRNA Nanomaterials. (A) Schematic illustration of the synthesis process for nanomaterials, which are encapsulated in NPC cell membrane cores composed of iron-doped semiconducting polymer nanoparticles (Fe@Pdot). These nanoparticles carry siRNA targeting circADARB1 or a scrambled siRNA as a negative control (NC), referred to as Fe@Pdots-siRNA and Fe@Pdots-siNC, respectively. (B) Representative transmission electron microscopy (TEM) images of Pdots, Fe@Pdots, Fe@Pdots-siNC, and Fe@Pdots-siRNA. (C) Particle size distribution of the four iron-loaded nanomaterials: Pdots, Fe@Pdots, Fe@Pdots-siNC, and Fe@Pdots-siRNA. (D) Fourier-transform infrared (FTIR) spectroscopy analysis of the chemical composition and molecular structure of the four nanomaterials. (E) In vivo fluorescence imaging was performed on tumor-bearing nude mice intravenously injected with saline, Fe@Pdots, Fe@Pdots-siNC, or Fe@Pdots-siRNA (10 mg/kg body weight). Imaging was conducted at 0, 6, 12, and 24 hours post-injection to track the distribution and accumulation of the nanomaterials in tumor tissues. The yellow circles represent the sites of tumor inoculation. (F) After 12 hours, the mice were euthanized, and organs including the heart, liver, spleen, lungs, kidneys, and tumor tissues were collected. The biodistribution of the nanomaterials in these organs and NPC xenografts was further assessed through in vivo imaging. (G) To establish a tumor-bearing model, nude mice were subcutaneously injected with NPC cells (CNE2) into the right dorsal flank. After 14 days, when xenografts reached 100–150 mm³, mice were randomly divided into three groups (n = 12). On days 14 and 20, each group received intravenous injections of saline, Fe@Pdots-siNC, or Fe@Pdots-siRNA (10 mg/kg body weight). Half of the mice in each group (n = 6) received 6 Gy X-ray irradiation at the tumor site (IR). Tumor sizes were measured every 3 days, and mice were euthanized on day 29. (H) At the end of the study, xenograft tumors were excised, and their volumes and weights were measured. **p < 0.01, ****p < 0.0001. Reproduced from Wang D, Tang L, Chen M, et al. Nanocarriers targeting circular RNA ADARB1 boost radiosensitivity of nasopharyngeal carcinoma through synergically promoting ferroptosis. ACS Nano. 2024;18(45):31055–31075.. Copyright 2024, American Chemical Society.

Figure 4

Characterization of USPIO-PEG-sLex nanoparticles. (A) Transmission electron microscopy (TEM) image of USPIO-PEG-sLex nanoparticles, revealing predominantly square and polygonal shapes, with a few spherical particles. (B) Particle size distribution of USPIO-PEG and USPIO-PEG-sLex. (C) Zeta potential measurements of USPIO-PEG (a) and USPIO-PEG-sLex (b). (D) Fourier-transform infrared (FTIR) spectra of USPIO-PEG and USPIO-PEG-sLex. Reproduced from Liu Q, Liu L, Mo C, et al. Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy. J Nanobiotechnology. 2021;19(1):171. © The Author(s) 2021. Creative Commons Attribution 4.0 International License.