Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy

Abstract

Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.

Multifunctional antibacterial hydrogels for chronic wound management

“…This structure undergoes a coagulation cascade with a coagulation factor exudate to stop the bleeding and temporarily protect the injured area. 24,25 Subsequently, inflammatory cells, including macrophages and neutrophils, converge at the wound location to clear foreign bodies, damaged endogenous tissues, apoptotic cells, and bacterial proteases. Meanwhile, other immune cells are attracted to the wound site via the release of reactive oxygen species (ROS), chemokines, vasoactive factors, and other mediators to aid in tissue restoration.…”

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies

“…210 Radiation not only induces DNA double-strand breaks and direct tumor cell death subsequently, but also may trigger the anti-tumor immune responses and provoke the remission of metastatic tumors outside of local radiation fields. 211,212 In addition, low-dose radiotherapy can contribute to the effective reprogramming of the TME, thus potentially surmounting the immunosuppressive substrate induced by high-dose radiotherapy. 213 In numerous clinical studies, radioimmunotherapy significantly increased the effective cure rate of patients compared to immunotherapy.…”

Modulation of the immunity and inflammation by autophagy

“…Employing nanoparticles as a strategy to manipulate autophagy represents a promising approach for cancer treatment. These nanoparticles, serving as effective delivery systems, offer potential in leveraging autophagy for therapeutic applications 167 …”

“…These nanoparticles, serving as effective delivery systems, offer potential in leveraging autophagy for therapeutic applications. 167 While certain drugs mentioned above, including rapamycin and HCQ, have been approved for human use, their clinical application was not specifically targeted toward autophagy regulation. 24 Additionally, the extent to which the pharmacological effects rely on autophagy remains uncertain.…”

“…These nanoparticles, serving as effective delivery systems, offer potential in leveraging autophagy for therapeutic applications. 167 …”