X-ray induced photodynamic therapy with copper-cysteamine nanoparticles in mice tumors

Abstract

Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray–induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide–conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule.

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

“…After collecting the suspension, the suspension was further centrifuged at 6000 rpm for 20 min, and the residue was collected, called small-sized nanoparticles. pH-low insertion peptide (pHLIP) [30], a tumor-targeting molecule that targets tumors based on pH, was conjugated to the different sized Cu-Cy nanoparticles in order to aid with tumor uptake, using the same methodology as Shrestha et al [20].…”

“…Copper-cysteamine (Cu-Cy) nanoparticle [15] is a novel sensitizer that can be activated by various excitation sources such as ultraviolet (UV) light [15,16], microwave (MW) [17,18], X-ray [7,15,19,20], and ultrasound (US) [21] as well as a cancer-specific intracellular stimulating agent (H 2 O 2 /acidic pH) [22] to produce reactive oxygen species (ROS) for cancer treatment. Furthermore, the combination of Cu-Cy and potassium iodide (KI) was able to destroy both Gram-positive and Gram-negative bacteria when excited by UV light [23].…”

“…Since the initial discovery of Cu-Cy nanoparticles [15], significant work has been done to understand the properties of the nanoparticles. Recently, a proof of concept has been undertaken to demonstrate that Cu-Cy nanoparticles can be used to significantly reduce tumor size in vivo when combined with radiation therapy, compared to radiation therapy alone [20].…”

“…Furthermore, radiation energy also affects the probability of radiation interactions, with the most common result being that higher radiation energies have lower interaction probabilities but higher radiation energy deposits per interaction on average [24]. Most radiation therapy done in clinics is with megavoltage sources, which are significantly higher than the radiation energies used in previous in vivo work [7,20].…”

Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy

“…28,43,44 The incorporation of photosensitizing ligands into Hf-based nMOFs further enhanced the radiotherapeutic efficacy by eliciting radiotherapy-radiodynamic therapy (RT-RDT) mode of action 29 rather than the established X-PDT process. [45][46][47] Herein, we report compositional ne-tuning of nMOFs by incorporating catalase-mimicking porphyrin-Fe centers to extend the anticancer effect of RT-RDT to hypoxic tumors. 48 The nMOF, Hf-DBP-Fe (DBP ¼ 5,15-di(p-benzoato) porphyrin), was synthesized via postsynthetic metalation of the previously reported Hf-DBP nMOF to embed biomimetic porphyrin-Fe III Cl centers as a functional mimic of the catalase active site.…”