Nanozyme-Incorporated Biodegradable Bismuth Mesoporous Radiosensitizer for Tumor Microenvironment-Modulated Hypoxic Tumor Thermoradiotherapy

Abstract

Solid tumors inevitably develop radioresistance due to low oxygen partial pressure in the tumor microenvironment. Despite numerous attempts, there are still few effective ways to avoid the hypoxia-induced poor radiotherapeutic effect. To overcome this problem, platinum (Pt) nanodots were fabricated into a mesoporous bismuth (Bi)-based nanomaterial to construct a biodegradable nanocomposite BiPt-folic acid-modified amphiphilic polyethylene glycol (PFA). BiPt-PFA could act as a radiosensitizer to enhance the absorption of X-rays at the tumor site and simultaneously trigger response behaviors related to the tumor microenvironment due to the enrichment of materials in the tumor area. During this process, the Bi-based component consumed glutathione via coordination, thus altering the oxidative stress balance, while Pt nanoparticles catalyzed the decomposition of hydrogen peroxide to generate oxygen, thereby relieving tumor hypoxia. Both Pt and Bi thus co-modulated the tumor microenvironment to improve the radiotherapeutic effect. In addition, Pt dots in BiPt-PFA had strong near-infrared absorption ability and created an intensive photothermal therapeutic effect. Modulation of the tumor microenvironment could thus improve the therapeutic effect in hypoxic tumors by a combination of photothermal therapy and enhanced radiotherapy. BiPt-PFA, as a biodegradable nanocomposite, may thus modulate the tumor microenvironment to enhance the hypoxic tumor therapeutic effect by thermoradiotherapy.

Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics

“…In addition, oxygen plays an important role in the process of ionizing radiation and killing of tumor cells, but the tumor microenvironment (TME) in solid tumors is threatened by oxygen depletion. All these features negatively affect the therapeutic efficacy of radiotherapy in clinical setting [ 80 – 82 ]. Considering the shortcomings of this single treatment, combination therapy may lead to improved therapeutic effect.…”

All‐In‐One Biomimetic Nanoplatform Based on Hollow Polydopamine Nanoparticles for Synergistically Enhanced Radiotherapy of Colon Cancer

“…Increasing the oxygen content in solid cancer tissue can significantly improve radiation sensitization. [43][44][45][46] Next, the ability of AVPt@HP@M to alleviate the intracellular hypoxia was evaluated. To this end, HCT-116 cells were cultured in a normal and hypoxia incubator.…”

Advances of Nanomedicine in Radiotherapy

“…Recently, noble metal nanoparticles, such as Au-based nanocomposites, have been extensively explored for the synergistic therapeutics of PTT and RT due to their strong NIR optical absorption [96][97][98][99][100][101][102]. For instance, Sun et al wrapped gold nanorods with tumor cell membranes to form novel nanocomposites (GNR@Mem).…”

“…In addition, this synthetic nanocomposite can increase the X-ray absorption of tumor tissues, consume glutathione, and catalyze the decomposition of peroxides to generate oxygen to relieve hypoxia in TME. Therefore, BiPt-PFA may be used as an ideal material to mediate the microenvironment and promote the sensitivity of tumors to photothermotherapy and radiotherapy [102].…”