Radiotherapy (RT), including external beam RT and internal radiation therapy, uses high-energy ionizing radiation to kill tumor cells. However, ionizing radiation inevitably damages the surrounding normal tissues. Therefore, it is imperative to develop precision RT for improving the treatment outcome and reducing the adverse effects. Recent breakthroughs in nanotechnology have provided a variety of strategies by which RT can precisely and efficiently eradicate local tumors. In this review, we would like to summarize a series of nanotechnology-mediated strategies to achieve precision RT, including tumor-targeted delivery, image-guided precision radiotherapy, and exo/endogenous stimuli-responsive nanomedicines for enhanced tumor accumulation/penetration. In addition, this review will also discuss two representative featured applications of precision RT: RT-induced immunotherapy against cancer metastasis and radioprotection of the surrounding healthy tissues. Since RT is usually thought to be only effective for treating local tumors, this review will interpret the unusual mechanisms of RT-mediated systemic antitumor immunity for eliminating distant cancer metastasis as well as the abscopal effects of RT in combination with other treatments (e.g., photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.). Furthermore, this review will discuss nanotechnology-mediated radioprotection strategies for shielding healthy tissues from radiation damage. Finally, the current challenges and future prospects of precision RT are also elucidated with the intention to accelerate its clinical translation.

The success of glioma chemotherapy is hampered by low intratumoral drug concentration and severe toxicity in normal organs. Glioma diagnosis and total tumor resection depend on enhanced magnetic resonance imaging (MRI) results which provide the best solution for recognizing tumor mass anatomical details with high spatial resolution. Zeolite imidazole frameworks (ZIFs) have pore channel tunability, large specific surface area and porosity, and have broad application prospects in adsorption, catalysis and drug loading. However, there are few reports on post-synthesis ZIF-8 based multifunctional nanocomposites as a theranostic agent for in vivo diagnostic and therapeutic applications simultaneously. In this study, we synthesized a low toxicity bimetallic zeolitic imidazolate framework (Mn-ZIF-8) with good dispersibility and high specific surface area, which could be used for potential high drug loading. Meanwhile, we used Mn-ZIF-8 for the first time for in vivo MRI. T₁-weighted MR signals at tumor sites continuously increased over time after injecting Mn-ZIF-8 intravenously. Moreover, 12 hours after injecting Mn-ZIF-8 into a nude mouse bearing U87-MG tumor, a relatively high accumulation of Mn²⁺ in tumors was observed, probably due to the EPR effect of cancerous tumors. Targeted delivery significantly improves the therapeutic efficacy of Mn-ZIF-8/5-Fu in U87-MG tumor-bearing mice, resulting in 80% survival rate over 40 days of treatment. Mn-ZIF-8/5-Fu has excellent in vivo biocompatibility at a given dose, which induces minimal side effects on the functions of important organs. Therefore, efficient 5-Fu loaded Mn-ZIF-8 with favorable in vivo biocompatibility, pH responsiveness and T₁-weighted contrast MRI of tumors can be used as a promising framework for diagnostic and therapeutic applications in the case of glioma simultaneously.

Excitatory hippocampal granule cells regulate activation and transition of quiescent neural stem cells during voluntary exercise.