Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications.

Nanoparticle-based radiosensitization of cancerous cells is evolving as a favorable modality for enhancing radiotherapeutic ratio, and as an effective tool for increasing the outcome of concomitant chemoradiotherapy. Nevertheless, delivery of sufficient concentrations of nanoparticles (NPs) or nanoparticle-based radiosensitizers (NBRs) to the targeted tumor without or with limited systemic side effects on healthy tissues/organs remains a challenge that many investigators continue to explore. With current systemic intravenous delivery of a drug, even targeted nanoparticles with great prospect of reaching targeted distant tumor sites, only a portion of the administered NPs/drug dosage can reach the tumor, despite the enhanced permeability and retention (EPR) effect. The rest of the targeted NPs/drug remain in systemic circulation, resulting in systemic toxicity, which can decrease the general health of patients. However, the dose from ionizing radiation is generally delivered across normal tissues to the tumor cells (especially external beam radiotherapy), which limits dose escalation, making radiotherapy (RT) somewhat unsafe for some diseased sites despite the emerging development in RT equipment and technologies. Since radiation cannot discriminate healthy tissue from diseased tissue, the radiation doses delivered across healthy tissues (even with nanoparticles delivered via systemic administration) are likely to increase injury to normal tissues by accelerating DNA damage, thereby creating free radicals that can result in secondary tumors. As a result, other delivery routes, such as inhalation of nanoparticles (for lung cancers), localized delivery via intratumoral injection, and implants loaded with nanoparticles for local radiosensitization, have been studied. Herein, we review the current NP delivery techniques; precise systemic delivery (injection/infusion and inhalation), and localized delivery (intratumoral injection and local implants) of NBRs/NPs. The current challenges, opportunities, and future prospects for delivery of nanoparticle-based radiosensitizers are also discussed.